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WO2025191283A1 - Oxidative method - Google Patents

Oxidative method

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Publication number
WO2025191283A1
WO2025191283A1 PCT/GB2025/050545 GB2025050545W WO2025191283A1 WO 2025191283 A1 WO2025191283 A1 WO 2025191283A1 GB 2025050545 W GB2025050545 W GB 2025050545W WO 2025191283 A1 WO2025191283 A1 WO 2025191283A1
Authority
WO
WIPO (PCT)
Prior art keywords
groups
group
pyridin
triazol
optionally substituted
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/GB2025/050545
Other languages
French (fr)
Inventor
Karen Solange VENEGAS
Marina FRANCA
Evangelia LIARI
Ronald Hage
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Catexel GmbH
Original Assignee
Catexel GmbH
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Filing date
Publication date
Application filed by Catexel GmbH filed Critical Catexel GmbH
Publication of WO2025191283A1 publication Critical patent/WO2025191283A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B11/00—Oxides or oxyacids of halogens; Salts thereof
    • C01B11/02—Oxides of chlorine
    • C01B11/022—Chlorine dioxide (ClO2)
    • C01B11/023—Preparation from chlorites or chlorates
    • C01B11/024—Preparation from chlorites or chlorates from chlorites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
    • B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
    • D—TEXTILES; PAPER
    • D21—PAPER-MAKING; PRODUCTION OF CELLULOSE
    • D21C—PRODUCTION OF CELLULOSE BY REMOVING NON-CELLULOSE SUBSTANCES FROM CELLULOSE-CONTAINING MATERIALS; REGENERATION OF PULPING LIQUORS; APPARATUS THEREFOR
    • D21C9/00—After-treatment of cellulose pulp, e.g. of wood pulp, or cotton linters ; Treatment of dilute or dewatered pulp or process improvement taking place after obtaining the raw cellulosic material and not provided for elsewhere
    • D21C9/10—Bleaching ; Apparatus therefor
    • D21C9/12—Bleaching ; Apparatus therefor with halogens or halogen-containing compounds
    • D21C9/14—Bleaching ; Apparatus therefor with halogens or halogen-containing compounds with ClO2 or chlorites

Definitions

  • the present invention relates to a method of generating chlorine dioxide from chlorite salts in the presence of an iron or manganese ion-containing complex, a method of treating a substrate with a chlorine-containing oxidant in the presence of an iron or manganese ion-containing complex and related aqueous media, kits and compositions.
  • chlorine dioxide as an oxidant is useful for a variety of applications, such as for disinfection of, and removal of manganese and iron metals via formation of their oxides from, (surface) water, treatment of industrial water, such as in cooling towers, for taste and odour control, and for the bleaching of cellulosic substrates, particularly wood pulp.
  • chlorine dioxide is also used in food processing, such as in the washing of fruit and vegetables, cleaning of animal processing equipment and animal carcasses, and treatment of poultry and animal habitats.
  • Chlorine dioxide serves as a highly selective oxidant owing to a unique one- electron transfer mechanism in which it is reduced to chlorite (see Alternative Disinfectants and Oxidants Guidance Manual, United States Environmental Protection Agency, 1999 (www.epa.gov/ogwdw/mdbp/alternative_disinfectants_guidance.pdf) in particular Chapter 4 thereof (“Chlorine Dioxide”)).
  • Chlorine dioxide is used widely for wood pulp bleaching and water treatment, the latter especially for antimicrobial activity, because it causes gross physical damage to bacterial cells and viral capsids.
  • the efficacy of chlorine dioxide is at least as good as that of elemental chlorine, with 2-4 log inactivation when using a few mgs/L of chlorine dioxide.
  • transition metal-based bleaching complexes have been studied to enhance the bleaching or delignification activity of hydrogen peroxide on wood pulp.
  • dinuclear manganese complexes based on triazacyclononane ligands are known to be particularly active complexes.
  • a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion, through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms, wherein the aqueous medium comprises a bisulfate or oxalate buffer, and the aqueous medium has a pH of about 1 to about 3.5.
  • a chlorite salt and (iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
  • the invention provides a composition comprising a chlorite salt, an acid comprising bisulfate or oxalate, and having a pKa in water at 25°C of about 1 to about 3.5 and one or more polydentate ligands, which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms.
  • the one or more polydentate ligands are not porphyrin or porphyrazine ligands.
  • the invention provides a kit comprising, as separate components:
  • polydentate ligands which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms.
  • the invention provides a kit comprising, separately:
  • a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or
  • a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
  • the invention permits alteration, e.g. improvement, of existing uses of chlorite salts in acidic conditions, for example so as to allow a reduction in the temperature at which, or the duration for which, these chemicals are used.
  • smaller dosages of chlorite salts may be used than are used in the absence of the iron or manganese complexes described herein, for example so as to obtain antimicrobial activity.
  • Another advantage of the invention is that, for example, solid chlorite salts in conjunction with an iron or manganese complex and an acid can be used for the antimicrobial applications, without needing to generate chlorine dioxide off line (i.e. ex situ).
  • the invention thus permits alteration, e.g. improvement, of existing formation of chlorine dioxide from chlorite in acidic media.
  • the present invention is based on the finding that complexes comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion, through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands, or complexes comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion, through at least three nitrogen atoms, can accelerate the conversion of chlorite to chlorine dioxide in acidic solutions having a pH of about 1 to about 3.5 and buffered by bisulfate or oxalate buffers, and thereby offer improvements or an alternative to existing methods and compositions used for the generation of chlorine dioxide from chlorite.
  • the methods of the first and third aspects of the invention involve use of, and the composition of the second aspect of the invention comprises, an aqueous medium with a pH of about 1 to about 3.5, which will generally have at least 1 wt% water, by which is meant that the water-containing liquid constituting the liquid aqueous medium comprises at least 1 % by weight water, more typically at least 10 wt%, even more typically 25 wt%, and most typically at least 50 wt% water.
  • the aqueous medium will be a solution (i.e. in which its various components, such as chlorite salt(s), acid and the iron or manganese complex are dissolved).
  • other aqueous i.e.
  • the aqueous medium comprises a liquid continuous phase, the liquid component of which is predominantly, i.e. between 50 and 100 wt% water, typically between 80 and 100 wt% water.
  • the liquid balance (if any) of the aqueous medium that is not water may be any convenient liquid, for example a liquid alcohol, e.g. a C1.4 alcohol such as methanol or ethanol. Where present, additional liquids will typically be water-miscible.
  • liquid continuous phase will often be entirely water, it will be understood that this does not exclude the presence of small amounts of other liquids (e.g. in a total amount of less than about 10 wt%, more typically less than about 5 wt%), e.g. as contaminants in the other materials with which the liquid continuous phases are brought into contact.
  • the liquid of the aqueous media described herein has a pH of about 1 to about 3.5.
  • the pH is about 1.5 to about 3.0, such as about 2 to about 2.5.
  • Solutions or other systems having this pH may be readily prepared by the skilled person.
  • appropriate buffers will allow control over the pH to be achieved and selection of appropriate buffers (in addition to bisulfate and/or oxalate buffers) is within the normal ability of those of normal skill.
  • Bringing the pH of the aqueous media to the desired value may be achieved by addition of appropriate amounts of an acid. This may be a solid acid, such as one having a pKa in water at 25°C of about 1 to about 3.5.
  • the aqueous medium comprises a bisulfate or oxalate buffer which may be present by addition of, for example, sodium bisulfate, potassium bisulfate, or oxalic acid.
  • the acid may first be dissolved in an appropriate amount of water or another suitable liquid, and the resultant composition may then be added to a composition comprising the chlorite salt and the iron or manganese complex.
  • a liquid form of an acid may be added to a composition comprising the chlorite salt and the iron or manganese complex.
  • the acid can be either used as obtained from a chemical supplier or it can be diluted in an aqueous medium prior to use.
  • the pH of the aqueous medium comprising the iron or manganese complex, chlorite salt and acid may be determined immediately after mixing the components. As chlorine dioxide is generated from the chlorite salt, the pH of the aqueous medium may increase above 3.
  • Suitable acids include those with pKa values of about 3.5 or lower.
  • pKa values herein relate to determinations conducted in water, at 25°C, for the reaction AH H + + A; wherein AH denotes the acid and A' denotes the conjugate base, as described in the CRC Handbook of Chemistry and Physics, 91 st edition, 2010, Dissociation Constants of Organic Acids and Bases, and Dissociation Constants of Inorganic Acids and Bases, and the references cited therein.
  • the acid used is a bisulfate ([HSO4]'), for example, the conjugate base, A; is sulfate ([SO4] 2 '); where the acid used is hydrochloric (HCI), for example, the conjugate base is chloride (Cl").
  • HCI hydrochloric
  • the pKa of water at25°C is defined herein, as is generally recognised in the art, as being 14.0.
  • Suitable acids include sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
  • the aqueous medium may comprise a bisulfate or oxalate buffer, which may be provided by the addition of sodium bisulfate, potassium bisulfate, or oxalic acid, and also comprise a further acid, such as sulphuric acid, hydrochloric acid and/or hydrobromic acid.
  • the aqueous medium comprises a bisulfate buffer. In some embodiments, the aqueous medium comprises one or more acids selected from sodium bisulfate, potassium bisulfate and hydrochloric acid. Typically, the aqueous medium comprises one of such acids. In some embodiments, the aqueous medium comprises an acid selected from sodium bisulfate and potassium bisulfate, and further comprises hydrochloric acid.
  • the chlorite salt used in accordance with the various aspects of the invention is typically an inorganic chlorite salt, the nature of which is not critical to the operation of the invention.
  • One or more chlorite salts may be used in any given method although typically only one chlorite salt will be used.
  • Non-limiting examples of chlorite salts that may be used include sodium chlorite (NaCIO2), potassium chlorite (KCIO2), lithium chlorite (l_iCIO2), calcium chlorite (Ca(CIO2)2), barium chlorite (Ba(CIO2)2) and magnesium chlorite (Mg(CIC>2)2).
  • sodium chlorite or potassium chlorite is used. More typically, the chlorite salt used is sodium chlorite.
  • the method according to the first aspect of the invention comprises contacting, in an aqueous medium with a pH of about 1 to about 3.5, a chlorite salt and a complex comprising one or more iron or manganese ions (which complexes are interchangeably referred to herein as iron or manganese complexes) and one or more polydentate ligands (as defined herein).
  • a chlorite salt and a complex comprising one or more iron or manganese ions (which complexes are interchangeably referred to herein as iron or manganese complexes) and one or more polydentate ligands (as defined herein).
  • contacting may be achieved in a variety of ways.
  • an aqueous medium may be prepared, to which chlorite salt and metal complex are added, separately or in combination.
  • the chlorite salt may be added as a solid, for example as a powder or granulate, or as an optionally buffered solution in water.
  • the acid is a solid acid, it may be selected from sodium bisulfate, potassium bisulfate and oxalic acid.
  • the chlorite salt may be as defined above, and is preferably sodium chlorite.
  • the weight ratio of solid acid to chlorite salt and to iron or manganese complex depends on the desired concentrations of each component when combined with, e.g. dissolved into, an aqueous solution. Typically, the amount of the iron or manganese complex is much lower than that of the solid acid or chlorite salt, which can make precise dosing more difficult. Often, the iron or manganese complex is ‘diluted’ with a filler, for example in a granulated form, so the dosage of the complex is easier to achieve. Suitable fillers include sodium sulfate, sodium chloride, potassium chloride, potassium sulfate, magnesium sulfate, and calcium sulfate.
  • Granulated materials comprise granule particles, which are asymmetrical aggregates of powder particles.
  • Granulation methods are widely known in the art (see, for example, Shanmugam, Bioimpacts, 2015, 5(1), 55- 63).
  • Granule materials can be produced by means of moist granulation, dry granulation, or compaction, and by means of melt-solidification granulation.
  • Granulation of the solid composition may improve the storage stability of the iron or manganese complex. This approach to granulate iron or manganese complexes is well known in detergent formulations, especially in laundry detergents and automatic dishwash detergents.
  • Non limiting examples include W095/06710 (Unilever N.V.), WO94/21777 (Unilever N.V.), WO2017/153528 (Conopco INC., Unilever), WO2010/115582 (Clariant International Ltd.), WO2014/198368 (Weylchem Wiesbaden GmbH), WO2018/210442 (Weylchem Wiesbaden GmbH), EP1913124B (Clariant, Stuttgart GmbH), and WO2011/005827 (Procter and Gamble Company).
  • compositions in accordance with the fifth aspect of the invention may be added to a liquid medium to form a composition in accordance with the second aspect of the invention, which may be used in accordance with the first aspect of the invention.
  • kits in accordance with the sixth or seventh aspect of the invention may likewise be used to form a composition in accordance with the second aspect of the invention, which may be used in accordance with the first aspect of the invention.
  • the kit of the invention may take the form of a cartridge comprising separated compartments, for example of the type described in WO 2012/027216 A1 (supra), comprising the components of the kit, i.e. the chlorite salt, the acid and the polydentate ligand or iron or manganese complex.
  • the iron or manganese complex may be adsorbed (immobilised) on a solid support, permitting generation of chlorine dioxide by allowing water to flow through the cartridge.
  • iron or manganese complexes may be reused upon replacement of the chlorite salt.
  • the one or more chlorite salts in it are typically present at a concentration of about 0.01 to about 100 mM, for example about 1 to about 50 mM. It will of course be recognised that the skilled person will be able to employ an appropriate concentration of chlorite salt, as with concentrations/amounts of other components described herein, without undue burden.
  • the aqueous media of the various aspects of the invention comprise an alkali metal halide.
  • the alkali metal halide may comprise any alkali metal or halide. Typically, however, the alkali metal is selected from sodium, potassium and lithium, most typically sodium and potassium.
  • the halide may be any of chloride, fluoride, bromide or iodide. Typically, the halide is chloride. Mixtures of different alkali metal halides may be present within the aqueous media. Typically, however, the alkali metal halide is sodium chloride.
  • the aqueous medium may comprise about 10 mM to about 6 M of the alkali metal halide.
  • the aqueous medium may comprise about 15 mM to about 5 M, about 20 mM to about 4 M, about 25 mM to about 3 M, about 30 mM to about 2 M, about 35 mM to about 1 M, about 40 mM to about 0.8 M, or about 50 mM to about 0.6 M of the alkali metal halide.
  • the aqueous medium comprises about 100 mM to about 1 M, of alkali metal halide, such as about 100 mM to about 1 M of sodium chloride.
  • the complex comprises one or more iron ions.
  • a chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is meant a polydentate ligand capable of chelating one or more iron or manganese ions by the formation of coordinate bonds between three or more nitrogen atoms of the chelant and a common iron or manganese ion, chelation in this context and as the term is customarily used in the art requiring that the nitrogen atoms of the chelant coordinate to the same transition metal ion, in this case an iron or manganese ion.
  • the chelants are thus at least tridentate.
  • the chelant When bound to one iron or manganese ion, the chelant can be tridentate, tetradentate, pentadentate, hexadentate, heptadentate, or octadentate, with tridentate, tetradentate, pentadentate, hexadentate being most common. Further, some of the chelants described herein having a denticity of greater than six, for example eight, with octadentate ligands being capable of coordinating through eight nitrogen atoms.
  • chelation is then often achieved by the formation of coordinate bonds between four nitrogen atoms and a common iron or manganese ion: for example four of the eight nitrogen atoms in these octadentate chelants can chelate to a first iron or manganese ion and four of these nitrogen atoms can chelate to a second iron or manganese ion.
  • This is generally achieved by such octadentate ligands having two portions of their structure giving rise to two separate regions of chelation, often separated by a bridge, as is explained and exemplified in greater detail below with reference to specific polydentate ligands useful in accordance with the present invention.
  • the chelants of the invention capable of chelating at least one iron or manganese ion through at least three nitrogen atoms are chelants capable of chelating at least one iron or manganese ion through four, five or six nitrogen atoms.
  • a chelant capable of chelating at least one iron or manganese ion through four nitrogen atoms may have a denticity of greater than four, such a chelant does not permit chelation through five (or more) or three (or fewer) nitrogen atoms.
  • a chelant capable of chelating at least one iron or manganese ion through three nitrogen atoms may have a denticity of greater than three, such a chelant does not permit chelation through four (or more) or two (or fewer) nitrogen atoms and so on.
  • the denticity refers to the number of metal ion-binding donor atoms that can bind to a metal ion.
  • a chelant which is, for example, a tetradentate nitrogen donor thus refers to an organic molecule comprising four nitrogen atoms with lone pairs, which can bind to a common transition metal ion, which according to the present invention is an iron ion.
  • These nitrogen donor atoms may be either aliphatic, either tertiary, secondary or primary amines, or may belong to a heteroaromatic ring, for example pyridine.
  • the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formula (I) or (I- B): wherein: each D is independently selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1 - yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl and thiazol-2-yl, each of which may be optionally substituted by one or more groups independently selected from the group consisting of
  • R3 and R4 are independently selected from hydrogen, Ci-Csalkyl, Ci-Csalkyl-O- Ci-Csalkyl, Ce-CwaryloxyCi-Csalkyl, Ce-C aryl, Ci-Cshydroxyalkyl, Ce-CwarylCi-Cealkyl and Cs-C heteroarylCi-Cealkyl, and -(CH 2 )o- 4 C(0)OR5 wherein R5 is independently selected from: hydrogen, Ci-Csalkyl and Ce- aryl;
  • Q2 represents a bridge selected from the group consisting of a Ciwalkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ciwalkylene units and one Ce-warylene unit, which bridge is optionally substituted one or more times with independently selected Ci. 24 alkyl groups and OH groups; and
  • the or each R1 and R2 are independently selected from the group consisting of Ci- C 24 alkyl, Ce-warylCi-Cealkyl, Ce-waryl, Cs-CwheteroarylCi-Cealkyl, each of which may be optionally substituted by one or more groups selected from -F, -Cl, -Br, -OH, - OCi-C 4 alkyl, -NH-CO-H, -NH-CO-Ci-C 4 alkyl, -NH 2 , -NH-Ci-C 4 alkyl and -SCi-C 4 alkyl.
  • Such ligands i.e. of formula (I) and (l-B)
  • bispidons are known in the art as bispidons.
  • the following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of bispidons:
  • each D group is either unsubstituted or substituted with one or more, often one, Ci-C4alkyl groups;
  • each D group is an optionally substituted pyridin-2-yl
  • each D group is unsubstituted pyridin-2-yl group
  • Q2 is selected from -CH2CH2-, -CH2CH2CH2- and -CH2CHOHCH2-, each of which is optionally Ci-Cealkyl-substituted, with the bridge typically being unsubstituted;
  • each R1 and R2 group is independently selected from Ci-C24alkyl, Ce-Cwaryl,
  • R1 or R2 group is independently a Ci-C24alkyl, a Ce-C aryl, or a Ce-warylCi-Cealkyl group, it is more typically independently selected from Ci- C alkyl and Ce-C arylCi-Cealkyl, and even more typically independently selected from: Ci-Csalkyl and Ce-C arylCH2;
  • R1 or R2 is independently a Cs-C heteroarylCH2 group, it is preferably selected from pyridin-2-ylmethyl, pyrazin-2-ylmethyl, quinolin- 2-ylmethyl, pyrazol-1-ylmethyl, pyrazol-3-ylmethyl, pyrrol-2-ylmethyl, imidazol-2- ylmethyl, imidazol-4-ylmethyl, benzimidazol-2-ylmethyl, pyrimidin-2-ylmethyl, 1 ,2,3-triazol-1 -ylmethyl, 1,2,3-triazol-2-ylmethyl, 1 ,2,3-triazol-4-ylmethyl, 1,2,4- triazol-3-ylmethyl, 1 ,2,4-triazol-1-ylmethyl and thiazol-2-ylmethyl, with pyridin-2- ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, and thiazol-2-ylmethyl being
  • R1 and R2 groups • often one of the R1 and R2 groups is Ci-C24alkyl or Ce-warylCi-Cealkyl, whilst the other of the R1 and R2 groups is a Cs-C heteroarylCH2 group or CH 2 CH 2 N(R10)(R11), whereby -N(R10)(R11) is selected from -NMe 2 , -NEt 2 , -
  • one of the R1 and R2 groups is most typically Ci-C alkyl, with Ci -Ci 2 alkyl more preferred, Ci-Csalkyl even more preferred and with CH3 being most preferred; and the other R1 or R2 group typically an optionally substituted pyridin-2- ylmethyl, with unsubstituted pyridin-2-ylmethyl being most typical, or is selected from CH 2 CH 2 N(R10)(R11), whereby -N(R10)(R11) is selected from -NMe 2 , -NEt 2 , - N(i-Pr) 2 ,
  • R1 is the same as R2 (for formula (I)) or each R1 is the same (for formula (II)), often methyl or pyridin-2-ylmethyl;
  • the bispidon is one of the following ligands: dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate (N2py3o-C1), dimethyl 2,4-di-(2-pyridyl)-3- (pyridin-2-ylmethyl)-7-methyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate (N2py3u-C1), and the iron complexes thereof (FeN2py3o-C1 , FeN2py3u-C1) which are described in WO 02/48301.
  • Another particular preferred bispidon is dimethyl 9,9- dihydroxy-3-methyl-2,4-di-(2-pyridyl)-7-(1-(N,N-dimethylamine)-eth-2-yl)-3,7-diaza- bicyclo[3.3.1]nonane-1 ,5-dicarboxylate and the iron complex thereof as described in WO 03/104234.
  • the analogous 3-pyridin- 2ylmethyl)-7-alkyl isomeric ligands and their iron complexes thereof are preferred. Examples of such bispidons are described in WO 02/48301 , WO 03/104379 and WO 2005/049778.
  • Also preferred tetradentate bispidons in particular, dimethyl 2,4-di-(2- pyridyl)-3,7-dimethyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate (N2py2), dimethyl 2,4-di-(2-pyridyl)-3,7-dibutyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5- dicarboxylate; dimethyl 2,4-di-(2-pyridyl)-3,7-dioctyl-3,7-diaza-bicyclo[3.3.1]nonan-9- one-1 ,5-dicarboxylate; and dimethyl 2,4-di-(2-pyridyl)-3,7-dibenzyl-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate.
  • the chelant capable of chelating at least one iron ion or manganese through nitrogen atoms is of formulae (II) and (ll-B):
  • each Q is independently selected from -CR4R5CR6R7- and -CR4R5CR6R7CR8R9-;
  • R4, R5, R6, R7, R8, and R9 are independently selected from: H, Ci-C4alkyl and hydroxyCi-C4alkyl; each R1 , R2, and R3 is independently selected from the group consisting of hydrogen, Ci-C24alkyl, CH2CH2OH, CH2COOH, CH2PO3H2, Cs-C heteroarylCi-Cealkyl and CH 2 CH 2 N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a
  • Q2 is a bridge selected from the group consisting of a Ci. ealkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ci-salkylene units and one Ce- arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups.
  • each R1 is independently selected from the group consisting of pyridin-2- ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, benzimidazol-2-ylmethyl, pyrazin-2- ylmethyl, pyrazol-1-ylmethyl, pyrazol-3-ylmethyl, 1 ,2,3-triazol-1 -ylmethyl, 1 ,2,3-triazol-2- ylmethyl, 1 ,2,3-triazol-4-ylmethyl, 1 ,2,4-triazol-1-ylmethyl, 1 ,2,4-triazol-3-ylmethyl, thiazol-2-ylmethyl and CH 2 CH 2 N(R10)(R11); each R2 is independently selected from: hydrogen, Ci-C 2 4alkyl, CH 2 CH 2 OH, CH 2 COOH and CH 2 PO 3 H 2 ; and
  • R3 is selected from the group consisting of H, Ci- 2 4alkyl, CH 2 CH 2 OH, CH 2 COOH and CH 2 PO 3 H 2 .
  • a ligand is of formula (ll-B), the ligand is symmetrical, i.e. each R1 is the same and each R2 is the same; and each Q group at the same position (e.g. between the bridging moiety-bearing and R2-substituted nitrogen atoms) in each ring is the same;
  • each Q is the same, for example each Q is -CR4R5CR6R7-, in which R4, R5, R6 and R7 are often H, which limitation defines the class of ligands often known as 1 ,4,7-triazacyclononane ligands;
  • R1 , R2, and/or R3 is a Cs-C heteroarylCi-Cealkyl group, such groups are selected from pyridin-2-ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, benzimidazol-2-ylmethyl, pyrazin-2-ylmethyl, 1 ,2,4-triazol-3-ylmethyl, 1 ,2,4- triazol-1 -ylmethyl, thiazol-2-ylmethyl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3- triazol-4-yl, pyrazol-3-ylmethyl and pyrazol-1 -ylmethyl,;
  • R1 , R2, and/or R3 are often independently Ci-C 2 4alkyl, pyridin-2-ylmethyl, or quinolin-2-ylmethyl.
  • R1 , R2, and/or R3 is a heteroaryl methyl group this will often be pyridin-2- ylmethyl;
  • -R1 , -R2, and/or -R3 (such as, and in particular when the complex is a manganese complex, R1) is -CH 2 CH 2 N(R10)(R11) in which any R10 and/or R11 moiety referred to as being optionally substituted with one or more Ci.
  • 2 oalkyl groups is typically either unsubstituted or only substituted with one Ci-2oalkyl group;
  • R1 , R2, and/or R3 (such as, and in particular when the complex is a manganese complex, R1) is CH2CH2N(R10R11), non-limiting examples of such groups include: di(p-methylbenzyl)amino, as an example of a di(C6-ioarylCi.
  • 4alkyl)amino pyrrolidinyl, piperidinyl or morpholinyl, as examples of NR7; di(piperidinylethyl)amino, as an example of di(heterocycloalkylCi-6alkyl)amino; and di(pyridin-2-ylethyl)amino, as an example of a di(heteroarylCi-6alkyl)amino.
  • each -N(R10)(R11) is independently selected from the group consisting of -NMe2, -NEt2, -N(/-Pr)2,
  • R1 , R2 and/or R3 (such as, and in particular when the complex is a manganese complex, R2) is Ci-C24alkyl, this is a Ci-Cealkyl, and often methyl;
  • R3 is Ci-C24alkyl, more typically a Ci-Cealkyl, and often methyl and is typically the same as R2;
  • bridge Q2 is typically Ci-ealkylene, often ethylene or n-propylene, and most often ethylene.
  • ligands of formula (II) or (II- B) are selected from the group consisting of 1 ,4,7-trimethyl-1 ,4,7-triazacyclononane (Mes-TACN), 1 ,2-bis(4,7-dimethyl-1 ,4,7-triazacyclonon-1-yl)-ethane (Me4-DTNE), 1- (pyridin-2-ylmethyl)-4,7-dimethyl-1 ,4,7-triazacyclononane, 1 ,4-bis(pyridin-2-ylmethyl)-7- methyl-1 ,4,7-triazacyclononane, 1 ,4, 7-tris(pyridin-2-ylmethyl)- 1 ,4,7-triazacyclononane, 1 ,2-bis(4-methyl-7-pyridin-2-yl-1 ,4,7-triazacyclononanethane, 1 ,3-bis(4-methyl-7- pyr
  • ligands of formula (II) are selected from 1-(pyridin-2-ylmethyl)-4,7-dimethyl-1 ,4,7-triazacyclononane and 1 ,4- bis(pyridin-2-ylmethyl)-7-methyl-1 ,4,7-triazacyclononane.
  • Q2 is a bridge selected from the group consisting of a C 2 -6alkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce-C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci- 2 4alkyl groups; and
  • Ri-Re are each independently selected from: H, Ci-4alkyl and hydroxyCi.4alkyl.
  • each R is independently hydrogen or is selected from the group consisting of Ci-C2oalkyl, C2-C2oalkenyl, C2-C2oalkynyl, Ce-Cwaryl and C?-C2oarylalkyl, each of which may be optionally substituted with Ci-Cealkyl.
  • Q2 which may be present in chelants of formula (III), is an ethylene or n- propylene bridge;
  • each -Q- is independently selected from -N(R)(CH2)2- and -N(R)(CH2)s-;
  • each -Q1- is independently selected from -N(R’)(CH2)2- and -N(R’)(CH2)s-;
  • each R is each selected from: hydrogen, Ci-C2oalkyl, Ce-C aryl, C?-C2oarylalkyl, pyridin-2-ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, benzimidazol-2- ylmethyl, more typically hydrogen, methyl, ethyl, benzyl, or pyridin-2-ylmethyl, yet more typically hydrogen, methyl, or benzyl;
  • each R is selected from: hydrogen, Ci-C2oalkyl and Ce-Cwaryl, more typically hydrogen, a Ci-C2oalkyl group, a Ce-Cwaryl group or a C?-C2oarylalkyl group, more typically still hydrogen, methyl, ethyl, or benzyl;
  • Ri-Re are each typically hydrogen or Ci-4alkyl, more typically still hydrogen or methyl, for example hydrogen;
  • the ligand is of formula (lll-A), i.e. a cross-bridged tetraaza-1 ,4,8,11- cyclotetradecane ligand: wherein R is as defined for formulae (III) and (IV) above, including the particular embodiments immediately hereinbefore described.
  • R is as defined for formulae (III) and (IV) above, including the particular embodiments immediately hereinbefore described.
  • each R in formula (lll-A) is independently selected from the group consisting of methyl, ethyl and benzyl.
  • each R is the same, often methyl.
  • Suitable cross-bridged ligands are described in in WO 98/39098 A1 (The University of Kansas).
  • the ligand of formula (III) or formula (lll-A) is 4,11-dimethyl-1 ,4,8,11-tetraazabicyclo[6.6.2]hexadecane.
  • Typical ligands of formula (IV) are tetraaza-1 ,4,7,10-cyclododecane and tetraaza-1 , 4, 8, 11 -cyclotetradecane, in either of which each of the hydrogen atoms attached to the four nitrogen atoms may be independently substituted for a Ci-C2oalkyl, Ce-Cioaryl or a C7-C2oarylalkyl group.
  • ligands of formula (IV) may be tetraaza-1 , 4, 7, 10-cyclododecane-based and tetraaza-1 , 4, 8, 11- cyclotetradecane-based ligands of formula (IV) wherein each R group is hydrogen, Ci- 2oalkyl, or heteroarylmethyl. Within these ligands, R is typically hydrogen, methyl, or pyridin-2ylmethyl. According to particular embodiments, ligands of formula (IV) include
  • ligands of formula (IV) may be tetraaza-1 , 4, 7, 10-cyclododecane-based and tetraaza-
  • ligands of formula (IV) include 1 ,4,7,10- tetraazacyclododecane, 1 ,4, 7, 10-tetramethyl-1 , 4, 7,10-tetraazacyclododecane,
  • the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formulae (V), (V-B) or (V-C):
  • each -R1 independently is selected from -CH2N(Ci-C24alkyl)2, -CH2NR7 or an optionally Ci-Cealkyl-substituted heteroaryl group selected from pyridin-2-yl, pyrazineyl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1-yl, 1 ,2,4-triazol-3-yl and thiazol-2-yl; each -R2 independently represents -R4-R5; each -
  • Q2 represents a bridge selected from the group consisting of a Ci-ealkylene moiety Ce- arylene moiety or a moiety comprising one or two Ciwalkylene units and one Ce- arylene unit, which bridge is optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups.
  • no -R3 or -Re may be one of the possibilities permitted for -R1.
  • ligands of formulae (V-B) and (V-C) are effectively dimers of ligands of formula (V) in which bridge Q2 takes the place of the R6 groups, or the R3 groups respectively.
  • ligands of formula (V) are most typical.
  • ligands of formula (V-B) more typical than ligands of formula (V-C).
  • R1 is optionally substituted pyridin-2-yl, in particular unsubstituted pyridin-2-yl;
  • -R4- is -CH 2 -.
  • R5 is optionally substituted pyridin- 2-yl, with the unsubstituted pyridin-2-yl being most typical;
  • R5 may be -CH2N(Ci-C24alkyl)2 group or -CH2NR7, the nitrogen-containing group attached to the methylene group recited for these possibilities being selected from the group consisting of NMe2,
  • each R3 and each R6 independently represents hydrogen, or a group selected from Ci-Cealkyl, Ce-C aryl, Ce-C arylCi-Cealkyl, Cs-Cwheteroaryl, Ce-C arylCi- Cealkyl and Cs-C heteroarylCi-Cealkyl, each of which groups may be optionally Ci-Cealkyl-substituted;
  • each R3 and each R6 independently represents hydrogen, or a group selected from Ci-Cealkyl, Ce- C aryl and Ce-C arylCi-Cealkyl, each of which groups may be optionally Ci- Cealkyl-substituted;
  • each R3 is selected from hydrogen, methyl and benzyl
  • Q2 is selected from-CH2CH2-, -CH2CH2CH2- and -CH2CHOHCH2-, each of which is optionally Ci-Cealkyl-substituted, with the bridge typically being unsubstituted;
  • each R6 is typically selected from hydrogen, methyl, benzyl, and pyiridin- 2ylmethyl, with R6 most typically being selected from methyl and pyiridin- 2ylmethyl;
  • each R6 is typically selected from hydrogen, methyl, and benzyl, with R6 most typically being methyl.
  • the ligand of formula (V) is N-methyl-N-
  • N4Py N,N-b/s(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine
  • N4Py N,N-b/s(pyridin-2-yl-methyl)-1 , 1 -bis(pyridin-2-yl)-1 - aminoethane
  • MeN4py N,N-bis(pyridin-2-yl-methyl-1 , 1- bis(pyridin-2-yl)-2-phenyl-1 -aminoethane as disclosed in EP 0 909 809.
  • ligands of formula (V) include: N-methyl-N-(pyridin-2-ylmethyl)-1 ,1- bis(pyridin-2-yl)-1 -aminoethane, N-benzyl-N-(pyridin-2-ylmethyl)-1 ,1-bis(pyridin-2-yl)-1- aminoethane, N-methyl-N-(pyridin-2-ylmethyl)-1 ,1-bis(pyridin-2-yl)-2-phenyl-1- aminoethane and N-benzyl-N-(pyridin-2-ylmethyl)-1 ,1-bis(pyridin-2-yl)-2-phenyl-1- aminoethane.
  • Another example of ligand of formula (V) is N-methyl-N-(pyridin-2-yl- methyl)-bis(pyridin-2-yl)methylamine.
  • the ligand of formula (V-B) is selected from N-methyl- N,N’,N’-tris(pyidin-2-ylmethyl)ethylenediamine, N-butyl-N,N’,N’-tris(pyridin-2-ylmethyl)- 1 ,2-ethylene-diamine, N-octyl-N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene-diamine, N, N, N’, N’-tetrakis(pyridin-2-yl-methyl)ethylene-1 ,2-diamine, N, N, N’, N’- tetrakis(benzimidazol-2-ylmethyl)ethylene-1 ,2-diamine, and 2,6-bis(pyridin-2-ylmethyl)- 1 ,1 ,7,7-tetrakis(pyridin-2-yl)-2,6- diazaheptane.
  • the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formula (VI):
  • each -R1 is independently selected from -CY2N(Ci-C24alkyl)2; -CY2NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci .ealkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; or represents an optionally Ci-Cealkyl- substituted heteroaryl group selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-1-yl, pyrazol-3-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol
  • -R1 is selected from -CH2N(Ci-C24alkyl)2 and -CH2NR7, with particular embodiments being those in which the nitrogen-containing group attached to the methylene group recited for these possibilities is selected from the group consisting of -NMe2, -NEt2, -N(i-Pr)2,
  • each R1 is often optionally substituted pyridin-2-yl
  • each R1 is more often unsubstituted pyridin-2-yl.
  • the ligand of formula (VI) is N,N,N- tr/s(pyridin-2-yl-methyl)amine (TPA), which has, for example, been described in US Patent Nos 5,850,086 (Que, Jr. et al.) and 6,153,576 (Blum et al.).
  • TPA N,N,N- tr/s(pyridin-2-yl-methyl)amine
  • the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formulae (VII) or (VII- B):
  • R1 R2N-X-NR1 R2 (VII); and R1 R2N-X-NR2(-Q2-R2N) n -X-NR1 R2 (Vll-B); wherein:
  • -X- is selected from -CY2CY2-, cis- or trans-1 ,2-cyclohexylene, -CY2CY2CY2-, - CY2C(OH)YCY2-, with each Y being independently selected from H, CH3, C2H5 and C3H7;
  • n is an integer from 0 to 10;
  • each R1 group is independently an alkyl, heterocycloalkyl, heteroaryl, aryl, arylalkyl or heteroarylalkyl group, each of which may be optionally substituted with a substituent selected from the group consisting of hydroxy, alkoxy, phenoxy, phosphonate, carboxylate, carboxamide, carboxylic ester, sulfonate, amine, mono- or dialkylamine and N + (R3)s, wherein R3 is selected from hydrogen, alkyl, alkenyl, arylalkyl, arylalkenyl, hydroxyalkyl, aminoalkyl, and alky
  • Q2 is a bridge selected from the group consisting of a Ci-ealkylene bridge, a Ce- arylene bridge or a bridge comprising one or two Ci.salkylene units and one Ce- arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups.
  • n is 1. In some cases, no R1 may be one of the possibilities permitted for R2.
  • X is typically -CH2CH2- or 1 ,2-cyclohexylene
  • Q2 is typically an ethylene, n-propylene bridge, or cis- or trans-1 ,2-cyclohexylene;
  • Q2 is typically an ethylene or n-propylene bridge
  • R4 for example where -R4 is -NR7 or -N(Ci-C24alkyl)2, is selected from the group consisting of -NMe2, -NEt2, -N(i-Pr)2,
  • R4 is selected from the group consisting of optionally Ci-Cealkyl- substituted pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3- triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1 -yl or thiazol-2-yl group, this will be typically be selected from optionally Ci-Cealkyl- substituted pyridin-2-yl, imidazol-2-yl, imidazol-4-yl or benzimidazol-2-yl group, with un
  • two R4 groups are selected from pyridin-2-yl, imidazol-2-yl, imidazol-4-yl, or benzimidazol-2-yl (each of which may be optionally Ci-Cealkyl-substituted), particularly wherein Z is hydrogen, more typically optionally substituted pyridin-2-yl wherein Z is hydrogen, and most typically unsubstituted pyridin-2-yl wherein Z is hydrogen (i.e.
  • two R2 groups (four in ligands of formula (Vll-B) are pyridin-2-ylmethyl); and/or two R1 groups are independently optionally substituted C1-C24 alkyl groups, more typically unsubstituted C1-C24 alkyl groups, for example C1-C18 alkyl groups, such as wherein two R1 groups are each methyl;
  • R1 groups in Formulae (VII) or (Vll-B) can be independently optionally substituted C1-C24 alkyl groups, more typically unsubstituted C1-C24 alkyl groups, for example C1-C18 alkyl groups, such as wherein one or both R1 groups are methyl;
  • R1 groups in Formula (VII) or (Vll-B) can be independently optionally substituted C6-C arylCi-C24alkyl groups, more typically unsubstituted C6-CioarylCi-C24alkyl groups, for example Ce-C arylCi-C ⁇ alkyl groups, most typically benzyl;
  • R1 groups in Formulae (VII) or (Vll-B) can be independently CZ2R4, wherein Z is as defined for moiety R2 and typically hydrogen, R4 can be an optionally Ci-Cealkyl-substituted pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol- 2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4- triazol-3-yl, 1 ,2,4-triazol-1 -yl, and thiazol-2-yl, this will be typically be selected from optionally Ci-Cealkyl-sub
  • R1 groups in Formulae (VII) or (Vll-B) are the same and typically selected from pyridin-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, or benzimidazol-2-ylmethyl;
  • one R1 group is the same as both R2 groups and typically all selected from pyridin-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4- ylmethyl, or benzimidazol-2-ylmethyl; equally often, both R1 groups are selected from pyridin-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, or benzimidazol-2-ylmethyl;
  • each R1 group is independently an alkyl, aryl or arylalkyl group, each of which may be optionally substituted with a substituent selected from the group consisting of hydroxy, alkoxy, phenoxy, phosphonate, carboxylate, carboxamide, carboxylic ester, sulfonate, amine, mono- or dialkylamine and N + (R3)s, wherein R3 is selected from hydrogen, alkyl, alkenyl, arylalkyl, arylalkenyl, hydroxyalkyl, aminoalkyl, and alkyl ether.
  • ligands of formula (VII) are N,N’-dimethyl-N,N’- bis(pyridin-2-ylmethyl)ethylene-1-2-diamine and N,N’-dimethyl-N,N’-bis(pyridin-2- ylmethyl)-cyclohexane-1-2-diamine, as disclosed by J Glerup et al. (Jnorg. Chern., 33, 4105-4111 (1994)).
  • Specific embodiments of ligands of formula (VII) wherein one R1 and two R2 are -CH2-R4 are described in WO 02/077145 and EP 1 001 009 A (trispicen ligands).
  • trispicen ligands are N-Ci-C2o-alkyl-N,N’,N’- tris(pyridin-2-ylmethyl)-1 ,2-ethylene-diamine, with N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)-1 ,2-ethylene-diamine, N-butyl-N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene- diamine, and N-octyl-N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene-diamine being most preferred.
  • the ligand Tpen (N, N, N’, N’-tetrakis(pyridin-2-yl-methyl)ethylene-1 ,2- diamine) is described in WO 97/48787.
  • the synthesis of the ligand N, N, N’, N’- tetrakis(benzimidazol-2-ylmethyl)ethylene-1 ,2-diamine has been described by S. Tong et al. (Open Journal of Inorganic Chemistry, 2, 75-80 (2012)).
  • Other suitable trispicens are described in WO 02/077145 and EP 1 001 009 A. Further examples of trispicens are described in WO 00/12667, W02008/003652, WO 2005/049778, EP 2 228 429 and EP 1 008 645.
  • the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formulae (VIII) or (VIII- B):
  • each Q group independently represents -CY2- or -CY2CY2-, in which each Y is independently selected from hydrogen, Ci-24alkyl, or a Ce- aryl; each D group independently represents a heteroarylene group or a group of the formula -NR-, with the proviso that at least one D group represents a heteroarylene group; each D1 group represents a group of the formula -NR’-; the two -R’ groups of the two D1 groups together form bridging moiety -Q2-; Q2 is a bridge selected from the group consisting of a Ci-ealkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce- C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; and each R group independently represents H, Ci-24alkyl, Ce- aryl or Cs-wheter
  • each R is typically independently selected from hydrogen or methyl
  • each R group is typically the same
  • each Q is typically -CY2-
  • Y is typically hydrogen and thus each Q is typically -CH2-;
  • a group D is heteroarylene, this is typically pyridylene, in particular pyridin- 2,6-diyl.
  • ligands of formula (VIII) are of formula (VIII- A), in which wherein R is as defined for formulae (VIII) and (Vlll-B), including the particular embodiments immediately hereinbefore described:
  • ligands of formula (VIII) are selected from 2,11-diaza[3.3](2,6-pyridinophane) (a compound of formula (VIII- A) in which each R is hydrogen) and N,N’-dimethyl-2,11-diaza[3.3](2,6-pyridinophane) (a compound of formula (Vlll-A) in which each R is methyl), as described in WO 99/065905 A1 (Unilever pic et al.).
  • the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formula (IX): R1-CY 2 -(NR3)-CY 2 -R2-CY 2 -(NR3)-CY 2 -R1 (IX) wherein: each Y is independently selected from H, CH3, C 2 Hs and C3H7; each R1 is independently selected from an optionally Ci-Cealkyl-substituted Cs- Cwheteroaryl group, whereby the Cs-Cwheteroaryl group is selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-y
  • R2 is selected from an optionally Ci-Cealkyl-substituted Cs-Ccheteroarylene group, whereby the Cs-Ccheteroarylene group is selected from pyridin-2,6-diyl, pyrazin- 2,6-diyl, pyrazol-3,5-diyl, pyrazol-1 ,3-diyl, pyrrol-2,5-diyl, imidazol-2,5-diyl, imidazol-1 ,4- diyl, pyrimidin-2,6-diyl, 1 ,2,4-triazol-3,5-diyl, 1 ,2,4-triazol-1 ,3-diyl, 1 ,2,4-triazol-2,4-diyl, 1 ,2,3-triazol-1 ,4-diyl, 1 ,2,3-triazol-1 ,4-diyl, 1 ,2,3-triazol-2,5
  • each R1 is independently selected from an unsubstituted Cs-Cwheteroaryl group, the Cs-Cwheteroaryl group being typically independently selected from pyridin-2- yl, quinolin-2-yl, imidazol-2-yl , and thiazol-2-yl;
  • R2 is typically unsubstituted pyridin-2,6-diyl
  • each R3 is independently selected from Ci-Cc substituted Ci- alkyl, Cc-warylCi- C alkyl, pyridin-2-ylmethyl, pyrazin-2-ylmethyl, quinolin-2-ylmethyl, pyrazol-1 - ylmethyl, pyrazol-3-ylmethyl, pyrrol-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4- ylmethyl, benzimidazol-2-ylmethyl, pyrimidin-2-ylmethyl, 1 , 2, 3-triazol-1 -ylmethyl, 1 ,2,3-triazol-2-ylmethyl, 1 ,2,3-triazol-4-ylmethyl, 1 ,2,4-triazol-3-ylmethyl, 1 ,2,4- triazol-1 -ylmethyl, and thiazol-2-ylmethyl;
  • each R3 is independently selected from unsubstituted Ci-i 2 alkyl, CcarylCi- Ci 2 alkyl, pyridin-2-ylmethyl, quinolin-2-ylmethyl, pyrazol-1 -ylmethyl, pyrazol-3- ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, benzimidazol-2-ylmethyl, 1 ,2,3-triazol-1 -ylmethyl, 1 ,2,3-triazol-2-ylmethyl, 1 ,2,3-triazol-4-ylmethyl, 1 ,2,4- triazol-3-ylmethyl, 1 , 2, 4-triazol-1 -ylmethyl, and thiazol-2-ylmethyl;
  • each R3 is independently selected from unsubstituted Ci-salkyl, CearylCH2, pyridin-2-ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, imidazol- 4-ylmethyl, benzimidazol-2-ylmethyl;
  • each R3 is independently selected from methyl, CH2C6H5, and pyridin-2-ylmethyl;
  • Y H
  • R1 pyridin-2-yl
  • R2 pyridin-2,6-diyl
  • R3 methyl, i.e. , is 2,6-bis[(A/-methyl- ⁇ A/-(2- pyridylmethyl) ⁇ amino)methyl]pyridine.
  • porphyrin or porphyrazine ligands Another class of ligands that may be present as polydentate ligands of the manganese complexes are porphyrin or porphyrazine ligands. These are described in detail in WO 2012/027216 A1 (The Trustees of Princeton University).
  • the parent compound is named porphyrine; when substituted, the resultant compounds are known as porphyrins.
  • porphyrazine derivatives comprising cyclic moieties fused to the 3- and 4-carbon atoms of the pyrrole moieties within porphyrazine are porphyrazines.
  • the complex does not comprise a porphyrin or porphyrazine ligand.
  • the polydentate ligand is not a tetrapyrrole-containing compound.
  • corrin rings comprise four pyrroline moieties linked by three methine bridges, all but one of the pyrroline moieties being connected at their 2- and 5-carbon atoms to an adjacent pyrroline moiety through a methine biradical; two of the pyrroline moieties, however, are directly connected, from the 2-carbon of one to the 5-carbon atom of the other.
  • Phthalocyanines are macrocycles comprising four pyrrole-based five-membered rings linked by four imine bridges, each of the five-membered rings having a benzene ring fused to the 3- and 4-positions of the five-membered ring, and each of the five-membered rings being connected at its 2- and 5-carbon atoms to an adjacent five-membered ring through an imine biradical.
  • each of these immediately aforementioned classes of macrocycle is excluded, it being understood that use of the term tetrapyrrole- containing compounds to embrace compounds not necessarily comprising four pyrrole rings is consistent with the use prevalent in the art to describe, as tetrapyrrole-containing compounds, compounds such as phthalocyanines and chlorins, even although these compounds, strictly speaking structurally, do not comprise four pyrrole rings.
  • the complex also comprises manganese ions, i.e. the complex is a manganese complex.
  • the complex is a manganese complex.
  • two of the pyrrole moieties within a porphyrin or porphyrazine ligand are deprotonated, and consequently negatively charged. Subsequently, the overall charge of the resultant manganese complex is reduced by 2.
  • double deprotonated porphyrin or porphyrazine ligands often stabilise manganese ions with a more positive oxidation state.
  • the one or more manganese ions have oxidation state(s) of one or more selected from the group consisting of II, III and IV.
  • the manganese complex further comprises up to two additional ligands independently selected from halide, oxo, aquo, hydroxo, cyanide, hydrogenphosphate, Ci-Csalcohol and Ci- Csalkoxide.
  • the porphyrin is of formula (X): wherein: each R 1 , R 2 , R 3 , and R 4 is a 5- to 10-membered N-heteroaryl optionally substituted with one or more selected from the group consisting of Ci-24alkyl, C3- scycloalkyl, C ⁇ cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci- 24alkylphenyl, Ci.24alkylnaphthyl, Ci.24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R 1a , R 2a , R 3a and R 4a is independently selected from the group consisting of Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci.24alkeny
  • the ligand is of formula (X-a):
  • n of formula (X) or (X-a) is 0.
  • R 1 , R 2 , R 3 , and R 4 of formula (X) or (X-a) are independently selected from formulae (X-b1), (X-b2), (X-b3) and (X-b4):
  • the R1, R2, R3 and R4 groups are the same.
  • the R5, Re, R7, Rs, Rg and R10 groups are methyl groups.
  • Preferred ligands of compound (X) are Tetra-(N-methyl)-2-pyridyl-porphyrin (TM2PyP), Tetra-(N-methyl)-4-pyridyl-porphyrin (TM4PyP), Tetra(N,N-dimethyl)- imidazolium-porphyrin (TDMImP), Tetra(N,N-dimethyl)-benzimidazolium-porphyrin (TDMBImP), and 5,10,15,20-tetra(4-pyridyl)-21 H,23H-porphine tetrakis(methochloride).
  • the porphyrazine ligand is of formula (XI): wherein: A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , C 1 , C 2 , C 3 , C 4 , D 1 , D 2 , D 3 and D 4 are independently selected from N, C-H, C-R n , N + -H and N + -R n with the proviso that no more than one of Ai, Bi, Ci , and Di is N, N + -H or N + -R n , no more than one of A2, B2, C2, and D2 is N, N + -H or N + -R n , no more than one of A3, B3, C3, and D3 is N, N + -H or N + -R n , and no more than one of A4, B4, C4, and D4 is N, N + -H or N + -R n , and wherein:
  • the ligand is of formula (Xl-a):
  • n of formula (XI) or (Xl-a) is 0.
  • each R n of formula (XI) or (Xl-a) is Ci-24alkyl, C3- scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, Ce- aryl, Ci.24alkynyl, Ci ⁇ alkylCe- aryl, Ci- 24alkoxy and phenoxy, each of which is optionally substituted with Ci-ealkyl, halo, CH2CF3 and CF3.
  • Di , D2, D3, and D4 are the same, often each being N + -R n .
  • a 1 , B 1 , C 1 , A 2 , B 2 , C 2 , A 3 , B 3 , C 3 , A 4 , B 4 , and C 4 are the same, often each being CH.
  • each R n is methyl.
  • a preferred ligand of formula (XI) is TM23PyPz, which is of formula (Xl-a):
  • the resultant polydentate ligands are capable of chelating two iron or manganese ions.
  • Such polydentate ligands, as well as the other polydentate ligands described herein may be readily accessed by the skilled person.
  • N-(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine N3py
  • the synthesis of which is described by G. Roelfes etal. J. Am. Chem.
  • Soc., 122, 11517-11518 (2000) may be reacted with, 1 ,2-dibromoethane, for example to yield 1 ,2-bis(N-(pyridin-2-yl- methyl)-bis(pyridin-2-yl)methylamine)-ethane, analogously to the synthesis of the TACN- bridged ligands described by K-0 Schaefer et al. (supra) or the procedure described by M Klopstra et al. (Eur. J. Inorg. Chem., 846-856 (2000)) involving reaction N3py with benzylchloride to produce benzyl-N3py.
  • ligands of formulae (V-C) N-methyl-N-(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine (MeN3py) (the synthesis of which is described by M Klopstra et al. (supra) may be reacted with BuLi at low temperature and then with, for example, dibromoethane to yield the bridged ligand, analogously to the synthesis of MeN4py and benzylN4py described elsewhere (see for example EP0909809B).
  • MeN3py N-methyl-N-(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine
  • N,N’-bis(2-pyridylmethyl)ethylene diamine prepared as described by L Xu et al (Inorg. Chem., 39, 5958-5963 (2000)
  • 1 ,3- dibromopropane analogously to the synthesis of the TACN-bridged ligands described by K-0 Schaefer et al. (supra)
  • 1 ,3-bis(N,N’-bis(2-pyridylmethyl)ethylene diamine)-propane prepared as described by L Xu et al (Inorg. Chem., 39, 5958-5963 (2000)
  • 1 ,3- dibromopropane analogously to the synthesis of the TACN-bridged ligands described by K-0 Schaefer et al. (supra)
  • methylation can be effected to access the methylated ligand, 1 ,3-bis(N,N’-dimethyl-N,N’-bis(2-pyridylmethyl)ethylenediamine)-propane, analogously to synthesis of MeN3py by M Klopstra et al. (supra).
  • ligands of formulae (Vlll-B) the skilled person will recognise, for example that 2,11-diaza[3.3](2,6-pyridinophane (see WO 99/065905 A1) can be reacted with 1 ,2-dibromoethane (analogously to the synthesis of the TACN-bridged ligands described by K-0 Schaefer et al. (supra)), to yield 1 ,2-bis(2,11-diaza[3.3](2,6- pyridinophane)ethane.
  • methylation can be effected to access the methylated ligand, 1 ,2-bis(11-methyl-2,11-diaza[3.3](2,6-pyridinophane)ethane, analogously to synthesis of MeN3py by M Klopstra et al. (supra).
  • Ligands of formula (IX) can be either prepared by procedures as outlined above for different bridged ligands via a reaction of the appropriate amine-based precursor with e.g. dibromo-ethane, but they may also be prepared by reacting the appropriate free polyamine precursor with e.g. picolinic chloride, via the well-established procedures to couple picolinic chloride to free amines (see various references of the examples given in the patent application).
  • polydentate ligands of formulae (l-B), (ll-B), (V- B), (V-C), (Vl-B), (Vll-B), (Vlll-B), and (IX) are often capable of chelating one iron or manganese ion and thus, of the chelants described above, chelants selected from the group consisting of ligands of formula (I), (II), (III), including (lll-A), (IV), (V), (VI), (VII), (VIII), including (Vlll-A), and (IX) are typical.
  • the chelant is selected from formula (I), (II), (ll-B), (III),
  • the chelant is selected from formula (I), (II), (IV),
  • the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, dimethyl 2,4-di-(2-pyridyl)-3-(pyridin-2- ylmethyl)-7-methyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, dimethyl 9,9- dihydroxy-3-methyl-2,4-di-(2-pyridyl)-7-(1-(N,N-dimethylamine)-eth-2-yl)-3,7-diaza- bicyclo[3.3.1]nonane-1 ,5-dicarboxylate, dimethyl 2,4-di-(2-pyridyl)-3,7-dimethyl-3,7- diaza-bicyclo
  • the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N, N-bis(pyridin-2-yl-methyl-1 , 1 - bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine, tris(pyridin-2-ylmethyl)amine, 1 ,4,7, 10-tetrakis(2-pyridin-2- ylmethyl)-1 ,4,7,10-tetraazacyclododecane, 1-ethyl-4,7-bis(quinolin-2-ylmethyl)-1 ,4,7- triazacyclononane and 2,6-bis(pyridin-2-yl
  • the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N, N-bis(pyridin-2-yl-methyl-1 , 1 - bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine, tris(pyridin-2-ylmethyl)amine, and 2,6-bis(pyridin-2-ylmethyl)- 1 ,1 ,7,7-tetrakis(pyridine-2-yl)-2,6-diazaheptane.
  • the chelant is dimethyl 2,4-di-(2-pyridyl)-3-methyl-7- (pyridin-2-ylmethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate.
  • the iron or manganese complexes referred to in connection with the various aspects of this invention are formed from a chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms, including the specific examples of such ligands described in detail herein.
  • These ligands comprise donor atoms, which coordinate to one or more iron or manganese ions of the iron or manganese complexes described herein.
  • the concentration of the iron or manganese complexes in the aqueous media described herein is typically about 0.001 to about 50 pM, often about 0.01 to about 20 pM, and according to particular embodiments about 0.03 to about 5 pM.
  • a well-defined complex is meant herein (as the term is used customarily in the art) a pre-formed complex (i.e. not one prepared in situ), which has been, or may be, isolated such that it is susceptible to characterisation (i.e. definition) and analysis (e.g. to determine its structure and degree of purity).
  • a complex that is not well- defined is one that is prepared in situ without isolation from the medium (e.g. reaction medium) in which it is prepared, and optionally used.
  • an appropriate iron or manganese complex may be prepared by mixing an appropriate amount of polydentate ligand with an appropriate amount and source of iron or manganese ions, in a desired stoichiometry.
  • iron salts are selected from the group consisting of optionally hydrated FeCh, FeBr2, Fe(NOs)2, FeSC , Fe(CFsSO3)2, Fe(acetylacetonate)2, Fe(acetylacetonate)3, Fe(RsCOO)3 (including Fe(acetate)3) and Fe(RsCOO)2, wherein Rs is selected from a Ci-C24alkyl.
  • the salt comprises two or more Rs groups, these can be the same or different.
  • the alkyl moieties by which is meant saturated hydrocarbyl radicals, may be straight-chain or comprise branched and/or cyclic portions.
  • the iron salt is selected from the group consisting of optionally hydrated FeCh, FeBr2, Fe(NOs)2, FeSO4 and Fe(OAc)2.
  • manganese salts are selected from the group consisting of optionally hydrated MnCh, MnBr2, Mn(NO3)2, MnSO4, Mn(acetylacetonate)2, Mn(acetylacetonate)3, Mn(RsCOO)3 (including Mn (acetate ⁇ ) and Mn(RsCOO)2, wherein Rs is selected from a C1-C24 alkyl.
  • the salt comprises two or more Rs groups, these can be the same or different.
  • the alkyl moieties by which is meant saturated hydrocarbyl radicals, may be straight-chain or comprise branched and/or cyclic portions.
  • the manganese salt is selected from the group consisting of optionally hydrated MnCl2, MnBr2, Mn(NO3)2, MnSO4 and Mn(OAc)2.
  • metal salts often contain water molecules within a crystal lattice, which will remain present unless the hydrated metals salts are subjected to specific drying steps by heating or drying under reduced pressure.
  • partially or fully dehydrated metal salts can also be used.
  • iron(ll)chloride, manganese (II) acetate and manganese (II) chloride can be bought as a tetrahydrate salt or as a dehydrated (anhydrous) salt.
  • Commercial iron sulfate is commercially available in dehydrated (anhydrous), monohydrate, and heptahydrate forms.
  • Commercial manganese sulfate is available in both tetrahydrate and monohydrate forms.
  • the complex used in accordance with the first and third aspect of the invention, or present in the composition of the second and fourth aspect, or kit of the seventh aspect of the invention is preformed (used interchangeably herein with the term “well-defined”). Often it is desirable to use preformed iron or manganese complexes.
  • iron or manganese complexes of use according to the various aspects of the invention are typically of the general formula (A1):
  • M represents an iron ion selected from Fe(ll), Fe(lll), Fe(IV) and Fe(V) or a manganese ion selected from Mn(ll), Mn(lll), Mn(IV) and Mn(V);
  • L represents the one or more polydentate ligands defined herein, or a protonated or deprotonated derivative thereof; each X independently represents a coordinating species selected from any mono-, bi- or tri-charged anion or a neutral molecule able to coordinate an iron or manganese ion in a mono-, bi- or tridentate manner, preferably selected from O 2 ', RBC>2 2 ' , RCOO; RCONR-, OH’, NO3 , NO, S 2 ’, RS; PO 4 3 ’, PO3OR 2 -, H 2 O, CO3 2 ; HCO3 , ROH, N(R) 3 , ROO; O 2 2 ’, O 2 ; RON, Ch, Br, OCN; SON; CN; N 3 ; F; h, RO; CIO 4 ; and CF3SOT , and more preferably selected from O 2 , RBO2 2 ; RCOO; OH; NOT, S 2 ;
  • Y is a non-coordinating counterion; a is an integer from 1 to 10, typically from 1 to 4, more typically still 1 or 2; k is an integer from 1 to 10 typically from 1 to 4, more typically still 1 or 2; n is an integer from 1 to 10, typically from 1 to 4; and m is zero or an integer from 1 to 20, and is typically an integer from 1 to 8.
  • the iron ion(s) of the complex are selected from the group consisting of Fe(ll), Fe(lll) and Fe(IV) and the manganese ion(s) of the complex are selected from the group consisting of Mn(ll), Mn(lll) and Mn(IV).
  • the complex comprises one or two such iron or manganese ions. Where the complex comprises two or more iron or manganese ions they may be of the same oxidation state or different oxidation states. Also where the complex comprises two metal ions, one metal ion may be iron and the second metal ion may be manganese.
  • alkyl is meant herein a saturated hydrocarbyl radical, which may be straightchain, cyclic or branched.
  • alkylene is meant an alkyl group from which a hydrogen atom has been formally abstracted. Typically alkyl and alkylene groups will comprise from 1 to 25 carbon atoms, more usually 1 to 10 carbon atoms, more usually still 1 to 6 carbon atoms. The simplest alkylene group is methylene (-CH2-).
  • alkenyl is meant an unsaturated hydrocarbyl radical, which may be straightchain, cyclic or branched, comprising one or more, typically one, non-aromatic carbon-carbon double bonds.
  • alkynyl is meant an unsaturated hydrocarbyl radical, which may be straightchain, cyclic or branched, comprising one or more, typically one, carbon-carbon triple bonds.
  • alkynylene is meant an alkynyl group from which a hydrogen atom has been formally abstracted. Typically alkynyl and alkynylene groups will comprise from 2 to 25 carbon atoms, more usually 2 to 10 carbon atoms, more usually still 2 to 6 carbon atoms.
  • heteroaromatic moieties may be regarded a subset of aromatic moieties that comprise one or more heteroatoms, typically oxygen, nitrogen or sulfur, often nitrogen, in place of one or more ring carbon atoms and any hydrogen atoms attached thereto.
  • heteroaromatic moieties for example, include pyridine, furan, pyrrole and pyrimidine.
  • Aromatic moieties may be polycyclic, i.e. comprising two or more fused aromatic (including heteroaromatic) rings.
  • Naphthalene and anthracene are examples of polycyclic aromatic moieties, and benzimidazole is an example of a polycyclic heteroaromatic moiety.
  • Aryl radicals and arylene diradicals are formed formally by abstraction of one and two hydrogen atoms respectively from an aromatic moiety.
  • phenyl and phenylene are the aryl radical and arylene diradical corresponding to benzene.
  • pyridyl and pyridylene are the heteroaryl radical and heteroarylene diradical corresponding to pyridine.
  • pyridyl and pyridylene are typically 2-pyridyl and pyridine- 2,6-diyl respectively.
  • heterocycloalkane is meant a cycloalkane, typically a Cs-ecycloalkane, in which one or more CH2 moieties are replaced with heteroatoms, typically selected from the group consisting of nitrogen, oxygen and sulfur. Where the heteroatom is nitrogen, it will be understood that the CH2 moiety is formally replaced with NH, not N.
  • heterocycloalkyl is meant herein a radical formed formally by abstraction of a hydrogen atom from a heterocycloalkane. Typical examples of heterocycloalkyl groups are those in which the heterocycloalkyl is formed formally by abstraction of a hydrogen atom from the nitrogen atom.
  • Typical heterocycloalkyl groups include pyrrolidin-1 -yl, piperidin-1-yl and morpholin-4-yl, i.e. in which the heterocycloalkyl is formed formally by abstraction of a hydrogen atom from the nitrogen atom of the parent heterocycloalkane.
  • arylalkyl is meant aryl-substituted alkyl.
  • aminoalkyl is meant amino-substituted alkyl
  • hydroxyalkyl is meant hydroxy-substituted alkyl and so on.
  • alkylene bridges are described herein. Such alkylene bridges are typically although not necessarily straight chain alkylene bridges. They may, however, be cyclic alkylene groups (e.g. a Cealkylene bridge may be cyclohexylene, and if so is typically cyclohexyl-1 , 4-ene). Where a bridge is, for example, a Ce-C arylene bridge, this may be, for example, phenylene or the corresponding arylene formed by abstraction of two hydrogen atoms from naphthalene.
  • a Ce-C arylene bridge this may be, for example, phenylene or the corresponding arylene formed by abstraction of two hydrogen atoms from naphthalene.
  • a bridge comprises one or two Ci-Csalkylene units and one Ce-C arylene unit
  • such bridges may be, for example, -CH2C6H4CH2- or - CH2C6H4-.
  • phenylene is typically phenyl-1 , 4-ene. It will be understood that each of these bridges may be optionally substituted one or more times, for example once, with independently selected C1-C24 alkyl (e.g. C1-C18 alkyl) groups.
  • carboxamide is meant a compound or radical comprising the functional group -N(H)C(O)-.
  • carboxylic ester is meant a compound or radical comprising the functional group -OC(O)-.
  • alkyl ether is meant a radical of the formula -alkylene-O-alkyl, wherein alkylene and alkyl are as herein defined.
  • the counter ions Y in formula (A1) balance the charge z on the complex formed by the ligand(s) L, iron or manganese ion(s) and coordinating species X. If the charge z is positive, as it is in most cases, the iron or manganese complex comprises one or more iron or manganese ions and one or more non-coordinating counteranions Y.
  • counteranions Y include RCOO; BPI , CIOT, BF4; PFe’, RSOT, RSOT, SO4 2 ; S20e 2 ' , NOT, F; Cl; Br, or I; with R being hydrogen, Ci-C4oalkyl or optionally Ci-C2oalkyl- substituted Ce-C aryl.
  • counterions Y include those which give rise to the formation of storage-stable solids.
  • counterions including those for the preferred metal complexes, are often selected from Cl; Br; I; NOT, CIOT, PFe; RSOT, SO4 2 ; RSOT, CF3SO3; and RCOO; with R in this context being selected from H, C1-12 alkyl, and optionally Ci-ealkyl-substituted CeHs (i.e. wherein CeHs is substituted one or more times (e.g. once) with a Ci-ealkyl group; often CeHs is unsubstituted).
  • these will be selected from Cl; NOT, PFe’, tosylate, SO4 2 ; CF3SO3; acetate, and benzoate. Particularly often, these will be selected from the group consisting of Cl; NO3; SC>4 2 ' and acetate.
  • suitable counterions include alkali metal ions, alkaline earth metal ions, (alkyl)ammonium cations (such as tetraCi.4alkylammonium cations), tetraarylphosphonium cations, and bis(triphenylphosphorananylidene)-ammonium cations for balancing the charge of the compound on a stoichiometric basis.
  • the tetraarylphosphonium cations include, for example, tetraphenylphosphonium ions, or related ions with four aryl or four alkyl groups on phosphorus including any combination of aryl or alkyl, including mixed aryl and alkyl groups on the same phosphorus atom.
  • the tetraalkylammonium ions may include, for example, tetraethyl ammonium, tetrapropyl ammonium and tetrabutyl ammonium ions, and tetralkyl ammonium ions with longer (e.g.
  • straight chain alkyl groups including ammonium ions with a combination of straight chain alkyl groups, or with four branched alkyl groups, or with mixtures of branched and straight chain alkyl groups. If z is negative, preferred counterions are those of alkali metal ions or alkaline earth metal ions, with Na + , K + , and Li + being particularly preferred.
  • Those complexes that comprise chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms are typically mononuclear iron or manganese complexes comprising other monodentate ligands (X according to formula (A1)).
  • suitable monodentate ligands include chloride, bromide or triflate (CFSSOT) anions. If for example iron(ll) or manganese(ll) species are used with chelants capable of chelating at least one iron or manganese ion through four neutral nitrogen atoms, two monanionic, monodentate ligands will neutralise the charge of the iron or manganese ion and no additional non-coordinating counterions will be present.
  • additional counterions X will be present, such as those defined in formula (A1), chloride, triflate or hexafluorophosphate being most preferred.
  • additional counterions X such as those defined in formula (A1), chloride, triflate or hexafluorophosphate being most preferred.
  • Other possibilities may be envisaged, such as a neutral tridentate nitrogen donor bound to an iron(lll) or manganese(lll) species, with three anionic monodentate ligands, such as chloride, bromide or triflate, rendering the charge of the complex zero.
  • neutral monodentate ligands such as acetonitrile or water
  • iron or manganese ion(s) may be bound to the iron or manganese ion(s). It will be understood that this possibility may also give rise to a charged iron or manganese complex (i.e. with a bound Fe(ll) or Mn(ll) ion), and thus occasions the presence of non-coordinating counterions.
  • This discussion is premised on an iron or manganese ion binding to 6 donor atoms. Although this is generally the case, it is not always so: Fe(ll), Mn(ll), Fe(lll) or Mn(lll) ions are, for example, known to give rise to, besides 6-coordinate complexes, 4, 5 or 7-coordinate complexes.
  • Complexes of formula (A1) typically comprise one or two iron or manganese ions.
  • dinuclear iron or manganese complexes i.e. iron or manganese complexes comprising two iron or manganese ions
  • additional bridging ligands include oxide (O 2- ), hydroxide (OH-) or Ci-ecarboxylate (i.e. RCC>2' wherein R is a Ci -salkyl group) ions, which bridge the two iron or manganese ions.
  • an alkylcarboxylate ion is typically acetate.
  • dinuclear complexes comprise two bridging ions, for example, two acetate ions.
  • the iron or manganese complex of use according to the various aspects of the invention is selected from the group consisting of [Fe(dimethyl
  • the iron or manganese complex of use according to the various aspects of the invention is selected from the group consisting of [Fe(dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate)CI]CI, [Fe(N,N-bis(pyridin-2-yl-methyl-1 ,1- bis(pyridin-2-yl)-1-aminoethane)CI]CI, [Fe(N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine)CI]CI, [Fe2(p-O)(p-CH3CC>2)(tris(pyridin-2- ylmethyl)amine)2](CIC>4)3, [Fe(1 , 4,7,10-tetrakis(2-pyridin-2-yl)
  • the iron or manganese complex of use according to the various aspects of the invention is selected from the group consisting of [Fe(dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate)CI]CI, [Fe(N,N-bis(pyridin-2-yl-methyl-1 ,1- bis(pyridin-2-yl)-1-aminoethane)CI]CI, [Fe(N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine)CI]CI, [Fe2(p-O)(p-CH3CC>2)(tris(pyridin-2- ylmethyl)amine)2](CIO4)3 and [Fe2(p-O)(p-CH3COO) 2,6-bis(pyridin
  • non-coordinating counterion(s) corresponding to Y of formula (A1)
  • additional coordinating stabilising ligand(s) corresponding to X of formula (A1)
  • a chloride counterion may be exchanged for a PFe counterion and/or a chloride coordinating stabilising ligand may be exchanged for a coordinating water ligand.
  • the substrate according to the third aspect of the invention need not be particularly limited and may be any substrate of which treatment with chlorine dioxide is desirable.
  • the substrate is, or comprises, a polysaccharide, for example cellulose or starch, often cellulose.
  • a particularly important embodiment in this respect is the treatment of wood pulp.
  • the present invention is of broad utility in the treatment of food products, including but not limited to fruit & vegetables, meat and fish; in the treatment of hard surfaces, including but not limited to the sanitation of poultry & animal processing equipment and poultry and animal habitats; and in the treatment of biofilms.
  • the aim is sterilisation: by treatment of a food product, for example, including but not limited to fruit, vegetables, meat and fish; a hard surface, such as those of equipment used in food processing (including poultry & animal processing), medical or laboratory equipment and equipment used in poultry and animal husbandry; and biofilms, for example on membranes, the aim is generally to effect sterilisation so as to eradicate or treat microorganisms, such as viruses, bacteria, and protozoa.
  • a food product for example, including but not limited to fruit, vegetables, meat and fish
  • a hard surface such as those of equipment used in food processing (including poultry & animal processing), medical or laboratory equipment and equipment used in poultry and animal husbandry
  • biofilms for example on membranes
  • biofilms are frequently found on membranes present in all types of filtration apparatus. All such membranes are susceptible to fouling with biofilms, particularly those found in reverse osmosis systems. Accordingly, treatment of substrates susceptible to the formation of biofilm is a particularly useful embodiment of the present invention: prevention and/or treatment of biofilms reduces the need for servicing and cleaning, and thus can lead to lower maintenance and system operating costs.
  • equipment susceptible to biofilm formation include, but are not limited to, pipes; cleaning (including laundry, dishwashing and bathing) equipment, such as sinks, baths, showers, dishwashers and washing machines, including the surfaces thereof (e.g. shower room walls and floors); cooling and heating systems; and marine apparatus (including hulls of ships and boats).
  • cleaning including laundry, dishwashing and bathing
  • sinks including laundry, dishwashing and bathing
  • washing machines including the surfaces thereof (e.g. shower room walls and floors); cooling and heating systems
  • marine apparatus including hulls of ships and boats.
  • the third aspect of the invention is of particular commercial utility in the treatment or prevention of biofilms, the method comprising treating any substrate on which a biofilm may be found, such as the equipment referred to in the previous paragraph.
  • the second aspect of the invention is also of particular commercial utility in the treatment of water.
  • the method according to the third aspect of the invention provides a method of treating water, comprising contacting the water with an amount of a chlorite salt; and a complex as defined herein.
  • the water that may be treated in accordance with the present invention is not limited. It may be, for example, water in municipal, commercial, industrial and domestic water systems, including drinking water, plant process water, cooling water or water found in swimming pools, boilers, conditioning equipment, or other industrial plant process water.
  • the substrate that is treated in accordance with the third aspect of the invention is or comprises a polysaccharide.
  • cellulosic substrates include primarily wood pulp and cotton (and thus cotton -containing material), as well as other plant-derived materials such as bagasse and jute. Treatment of cellulosic substrates is thus widespread, with the bleaching of both wood pulp and cotton being massive industries, cotton being subject to bleaching both in the treatment of raw cotton in the cotton-processing industry and also in laundry (domestic, industrial and institutional).
  • the objective of the treatment is to bleach these substrates, by which is meant the oxidative removal of undesirable contaminants.
  • these contaminants are generally polyphenolic materials, with lignin, which is responsible for the dark colour of unbleached wood pulp, comprising a significant proportion of wood.
  • the undesirable contaminants particularly targeted by bleaching include those responsible for stains.
  • wood pulp In order to produce high quality paper grades, wood pulp needs to be delignified and bleached to a sufficient extent to produce white pulp which is also stable towards light- and time-induced yellowing/ageing. Typically, wood is ground, pulped and then treated at high temperatures with alkaline sulfide or sulfite to remove the majority of the lignin. The thus-treated pulp is generally referred to as chemical pulp.
  • an oxygen delignification process is carried out, to remove about half of the lignin remaining in the chemical pulp. Then, this partly delignified pulp is often treated separately with chlorine dioxide and hydrogen peroxide. Dependent on the type of wood and the paper quality (brightness) desired, up to 2 to 3 separate steps employing chlorine dioxide and 1 to 2 stages with hydrogen peroxide are carried out. Alternatively, delignified and bleached pulp is frequently produced without the use of any chlorine-based bleaching chemicals, resulting in so-called total chlorine free (TCF) pulp.
  • TCF total chlorine free
  • chlorine dioxide is used mainly as a delignification agent (DO-stage).
  • elemental chlorine is also used as a bleaching chemical, which can give good activity in conjunction with chlorine dioxide.
  • Application of chlorine alone i.e. without chlorine dioxide
  • chlorine dioxide is no longer practised, since this can result in the formation of undesirably large amounts of chlorinated waste products.
  • chlorine dioxide is mainly used to further bleach the pulp, which contains small residues of lignin.
  • Loadings of chlorine dioxide in pulp mills are typically about 2 to about 10 wt% (with respect to oven-dry pulp), with processing carried out at about 40-100 °C.
  • the duration of the delignification varies but this typically from less than 1 h to 4 h.
  • the concentration of the chlorite salt in the aqueous media described herein is about 0.1 to about 50 mM for example about 5 to about 30 mM.
  • concentration of bleaching chemical such as chlorine dioxide
  • odp kg/ton oven dry pulp
  • Typical concentrations of chlorine dioxide currently used vary from about 5 to about 20 kg/ton odp.
  • the concentration of CI02 will be about 0.5 to about 2 g/L (which on a molar basis equates to about 7.4 to about 29.4 mM.
  • the amount of chlorite salt used in accordance with the present invention may be less than these whilst still retaining the desired extent of bleaching.
  • the skilled person will be able to determine the appropriate quantity of chlorite salt to use for any given method.
  • the composition of the second aspect is added into an aqueous solution comprising the water that needs to be treated, for example to achieve antimicrobial activity or to prevent formation of biofilm matter.
  • the resultant solution may comprise very low levels of chlorine dioxide, such as 1-30 mg/L
  • the compositions of the invention may comprise much higher levels of chlorine dioxide, such as 100-5000 mg/L.
  • the composition of the second aspect will contain about 300 to about 3000 mg/L of chlorine dioxide, the latter value determined by the solubility of chlorine dioxide in water at 25 °C. At lower temperatures, the solubility of chlorine dioxide in water is higher. However, about 3000 mg CIO2/L of water is often prepared. The skilled person will be able to determine the appropriate quantity of chlorine dioxide or chlorite salt to use for any given method.
  • a further advantage of the present invention arises from the reaction between hypochlorite and chlorite to form chloride and chlorine dioxide.
  • aqueous media e.g. solutions
  • hypochlorite which may be formed after reaction of chlorine dioxide with partially oxidised lignin residues (cf Pulp Bleaching, Principles and Practice, C. ⁇ N. Dence and D.W. Reeve, ed., Tappi, 1996, at pages 133-138).
  • Hypochlorite as a side product is less desirable as it may react with lignin residues to form chlorinated phenols.
  • hypochlorite reacts very efficiently with chlorite to form chloride and chlorine dioxide (cf Z Jia et al., Inorg. Chern., 39(12), 2614-2620 (2000)), and so will react chlorite salt present, preventing hypochlorite reacting further to yield chlorinated side products.
  • the amount of chlorite is generally much lower than that used in the context of pulp bleaching, typically about 1 to about 30 mg/l. Again, the skilled person will be able to determine the appropriate quantity of chlorine dioxide or chlorite salt to use for any given method.
  • the aqueous media of the invention has a pH of about 1 to about 3.5.
  • the chlorite salt and complex of the composition of the second aspect may be contacted within an aqueous medium comprising a bisulfate or oxalate buffer, and having a pH of about 1 to about 3.5.
  • the aqueous media of the invention has a pH of about 1 to about 3.5, more typically about 1.5 to about 3.0.
  • the concentration of the buffer is preferably about 1 mM to about 1 M; more typically about 5 mM to about 50 mM. If, for example, a pH of 2.0 is employed, the pKa of the buffer at the suitable concentration range should be 2.0 +/- 1.0 in order to have effective buffering capabilities.
  • Suitable buffers having low pKa values are well known in the art and include bisulfate (HSOT), and oxalic acid.
  • the cationic counterion of the bisulfate buffer can be chosen at will; preferred ones include sodium or potassium cations.
  • suitable buffers also act as suitable acids.
  • Suitable amounts of strong acids having pKa values of less than 1 may also be used (in addition to the buffer) to lower the pH of the aqueous media to the desired level.
  • the skilled person will be able to determine the desired amount of acid to be added by using a pH meter.
  • suitable strong acids include sulfuric acid, hydrobromic acid and hydrochloric acid.
  • mixtures of different acids may be used, for example a mixture of sodium bisulfate and hydrochloric acid, to further lower the pH of the aqueous media. Mixtures of different acids may be desirable over using only hydrochloric acid (with no buffering capacity at about pH 2) or only sodium bisulfate (where low pH values may difficult to achieve).
  • the temperature for practice of the methods of the invention may be determined by the skilled person. For example, cellulose treatment processes can be carried out at similar temperatures to those currently practised. Clearly, the optimum temperature will be substrate-dependent, and will often be about 50 to about 70 °C for wood pulp bleaching, although improved bleaching processes have been achieved by increasing the temperature, for example to treat eucalyptus wood pulp. However, it should be noted that the methods described herein may achieve the same bleaching activity at lower temperatures than those achievable absent the iron or manganese complexes described herein. Therefore, whilst the currently used temperature ranges for wood-pulp bleaching are typically about 50 to about 100 °C, use of the iron or manganese complexes described herein may allow these temperatures to be lowered.
  • temperatures of about 30 to about 100 °C are typical, for example about 40 to about 95 °C.
  • ambient temperatures e.g. 15 to 30 °C
  • the exact temperature can be determined without undue burden by those conducting any given method.
  • a chlorite salt, an acid comprising bisulfate or hydrogenoxalate with a pKa of about 1 to about 3.5 or an aqueous medium with a bisulfate or oxalate buffer and having a pH of about 1 to about 3.5, and an iron or manganese complex of the invention, such as that of formula (A1) is carried out under ambient conditions, with a preferred temperature of equal to or lower than about 35 °C.
  • a temperature typically equal to or lower than about 30 °C and more typically equal to or lower than about 25 °C will be employed.
  • Clause 1 A method of generating chlorine dioxide from a chlorite salt, comprising contacting, in an aqueous medium:
  • a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion, through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms; wherein the aqueous medium comprises a bisulfate or oxalate buffer, and the aqueous medium has a pH of about 1 to about 3.5.
  • Clause 2 The method according to clause 1 , wherein the pH is about 1.5 to about 3.0.
  • aqueous medium contains an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
  • Clause 5 The method according to clause 4, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid.
  • Clause 7 The method according to clause 6, wherein the alkali metal halide is sodium chloride.
  • Clause 8 The method according to clause 6 or clause 7, wherein the aqueous medium comprises about 10 mM to about 6 M of alkali metal halide.
  • Clause 11 The method of any one preceding clause, wherein the method involves use of a chlorite salt selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
  • a chlorite salt selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
  • Clause 14 The method of any one preceding clause, wherein the complex comprises one or more iron ions.
  • each D is independently selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3
  • R3 and R4 are independently selected from hydrogen, Ci-Csalkyl, Ci-Csalkyl-O- Ci-Csalkyl, Ce-CwaryloxyCi-Csalkyl, Ce-C aryl, Ci-Cshydroxyalkyl, Ce-CwarylCi-Cealkyl and Cs-C heteroarylCi-Cealkyl, and -(CH 2 )o- 4 C(0)OR5 wherein R5 is independently selected from: hydrogen, Ci-Csalkyl and Ce- aryl;
  • Q2 represents a bridge selected from the group consisting of a Ciwalkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ciwalkylene units and one Ce-warylene unit, which bridge is optionally substituted one or more times with independently selected Ci. 24 alkyl groups and OH groups; and
  • each Q is independently selected from -CR4R5CR6R7- and -CR4R5CR6R7CR8R9-;
  • R4, R5, R6, R7, R8, and R9 are independently selected from: H, Ci-C4alkyl and hydroxyCi-C4alkyl; each R1 , R2, and R3 is independently selected from the group consisting of hydrogen, Ci-C24alkyl, CH2CH2OH, CH2COOH, CH2PO3H2, Cs-C heteroarylCi-Cealkyl and CH 2 CH 2 N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a
  • Q2 is a bridge selected from the group consisting of a Ci. ealkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ci-salkylene units and one Ce- arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; wherein: each -Q- is independently selected from -N(R)C(RI)(R2)C(RS)(R4)- and -N(R)C(RI)(R 2 )C(R3)(R4)C(R 5 )(R6)-; each -Q1- is independently selected from -N(R’)C(RI)(R2)C(R3)(R4)- and -N(R’)C(RI)(R 2 )C(R3)(R4)C(R 5 )(R6)-; each R is independently hydrogen or is selected from the group consisting of Ci- C 2 oalkyl, C 2 -C 2 oalken
  • Q2 is a bridge selected from the group consisting of a C 2 -6alkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce-C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci- 2 4alkyl groups; and
  • Ri-Re are each independently selected from: H, Ci-4alkyl and hydroxyCi.4alkyl;
  • each -R1 is independently selected from -CH 2 N(Ci-C 2 4alkyl) 2 , -CH 2 NR7 or an optionally Ci-Cealkyl-substituted heteroaryl group selected from pyridin-2-yl, pyrazineyl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1-yl, 1 ,2,4-triazol-3-yl and thiazol-2-yl; each -R2 independently represents -R4-R5
  • each -NR7 independently represents a moiety in which R7 and the nitrogen atom N to which it is attached represents a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to R4 through the nitrogen atom N;
  • Q2 represents a bridge selected from the group consisting of a Ci-ealkylene moiety Ce- arylene moiety or a moiety comprising one or two Ci- 3 alkylene units and one Ce- arylene unit, which bridge is optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups;
  • each -R1 is independently selected from -CY2N(Ci-C24alkyl)2; -CY2NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci .ealkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; or represents an optionally Ci-Cealkyl- substituted heteroaryl group selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-1-yl, pyrazol-3-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol
  • each Y is independently selected from H, CH 3 , C2H5, C 3 H?; R1 R2N-X-NR1 R2 (VII); and R1 R2N-X-NR2(-Q2-R2N) n -X-NR1 R2 (Vll-B); wherein:
  • -X- is selected from -CY2CY2-, cis- or trans-1 ,2-cyclohexylene, -CY2CY2CY2-, - CY2C(OH)YCY2-, with each Y being independently selected from H, CH3, C2H5 and C3H7;
  • n is an integer from 0 to 10;
  • each R1 group is independently an alkyl, heterocycloalkyl, heteroaryl, aryl, arylalkyl or heteroarylalkyl group, each of which may be optionally substituted with a substituent selected from the group consisting of hydroxy, alkoxy, phenoxy, phosphonate, carboxylate, carboxamide, carboxylic ester, sulfonate, amine, mono- or dialkylamine and N + (R3)s, wherein R3 is selected from hydrogen, alkyl, alkenyl, arylalkyl, arylalkenyl, hydroxyalkyl, aminoalkyl, and alky
  • each Q group independently represents -CY2- or -CY2CY2-, in which each Y is independently selected from hydrogen, Ci-24alkyl, or a Ce- aryl; each D group independently represents a heteroarylene group or a group of the formula -NR-, with the proviso that at least one D group represents a heteroarylene group; each D1 group represents a group of the formula -NR’-; the two -R’ groups of the two D1 groups together form bridging moiety -Q2-;
  • Q2 is a bridge selected from the group consisting of a Ci-ealkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce- C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; and each R group independently represents H, Ci-24alkyl, Ce- aryl or Cs-wheteroaryl; and
  • R2 is selected from an optionally Ci-Cealkyl-substituted Cs-Csheteroarylene group, whereby the Cs-Csheteroarylene group is selected from pyridin-2,6-diyl, pyrazin- 2,6-diyl, pyrazol-3,5-diyl, pyrazol-1 ,3-diyl, pyrrol-2,5-diyl, imidazol-2,5-diyl, imidazol-1 ,4- diyl, pyrimidin-2,6-diyl, 1 ,2,4-triazol-3,5-diyl, 1 ,2,4-triazol-1 ,3-diyl, 1 ,2,4-triazol-2,4-diyl, 1 ,2,3-triazol-1 ,4-diyl, 1 ,2,3-triazol-2,5-diyl, and thiazol-2,5-
  • each R 1 , R 2 , R 3 , and R 4 is a 5- to 10-membered N-heteroaryl optionally substituted with one or more selected from the group consisting of Ci-24alkyl, C3- scycloalkyl, C ⁇ cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci- 24alkylphenyl, Ci.24alkylnaphthyl, Ci.24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R 1a , R 2a , R 3a and R 4a is independently selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R 1a , R 2a , R 3a and R 4a is independently selected from the group consisting of Ci-eal
  • a 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , C 1 , C 2 , C 3 , C 4 , D 1 , D 2 , D 3 and D 4 are independently selected from N, C-H, C-R n , N + -H and N + -R n with the proviso that no more than one of Ai, Bi, Ci , and Di is N, N + -H or N + -R n , no more than one of A2, B2, C2, and D2 is N, N + -H or N + -R n , no more than one of A3, B3, C3, and D3 is N, N + -H or N + -R n , and no more than one of A4, B4, C4, and D4 is N, N + -H or N + -R n , and wherein: each R n is independently selected from Ci-24alkyl, Cs-scycloalkyl
  • Clause 17 The method of clause 15, wherein the chelant is selected from formula (I), (II), (ll-B), (III), (IV), (V), (V-B), (VI) and (VII), such as (I), (II), (IV), (V), (V-B), (VI) and (VII).
  • Clause 18 The method of any one of clauses 1 to 14, wherein the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-
  • Clause 19 The method of any one of clauses 1 to 14, wherein the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-
  • a composition comprising:
  • an aqueous medium comprising a bisulfate, or oxalate buffer, and having a pH of about 1 to about 3.5;
  • a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
  • Clause 23 The composition of clause 22, wherein the pH is about 1 .5 to about 3.0.
  • Clause 24 The composition according to clause 22 or clause 23, wherein the aqueous medium is as defined in any one of clauses 3 to 9.
  • Clause 25 The composition of any one of clauses 22 to 24, wherein the chlorite salt is selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
  • Clause 26 The composition of clause 25, wherein the chlorite salt is sodium chlorite.
  • Clause 27 The composition of any one of clauses 22 to 27, wherein the complex is as defined in any one of clauses 12 to 21 .
  • Clause 28 A method of treating water or a substrate comprising contacting the water or the substrate with the composition defined in any one of clauses 22 to 27.
  • Clause 29 The method of clause 28, wherein the substrate is a cellulosic substrate.
  • Clause 30 The method of clause 29, wherein the substrate is wood pulp.
  • a solid composition comprising:
  • a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
  • Clause 32 The solid composition of clause 31 , wherein the pKa is about 1.5 to about 3.0.
  • Clause 33 The solid composition according to clause 31 or clause 32, wherein the solid acid comprises a bisulfate buffer.
  • Clause 34 The solid composition of any one of clauses 31 to 33, which comprises an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
  • Clause 35 The solid composition of clause 34, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid.
  • Clause 36 The solid composition of any one of clauses 31 to 35, which further comprises an alkali metal halide.
  • Clause 37 The solid composition of clause 36, wherein the alkali metal halide is sodium chloride.
  • Clause 38 The solid composition of any one of clauses 31 to 37, wherein the chlorite salt is selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
  • Clause 39 The solid composition of clause 38, wherein the chlorite salt is sodium chlorite.
  • Clause 40 The solid composition of any one of clauses 31 to 39, wherein the complex is as defined in any one of clauses 12 to 21 .
  • a composition comprising a chlorite salt, an acid comprising bisulfate or oxalate, having a pKa in water at 25°C of about 1 to about 3.5 and one or more polydentate ligands, which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms.
  • Clause 42 The composition of clause 41 , wherein the pKa is about 1.5 to about 3.0.
  • Clause 43 The composition according to clause 41 or clause 42, which comprises a bisulfate buffer.
  • Clause 44 The composition of any one of clauses 41 to 43, which comprises an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
  • Clause 45 The composition of clause 44, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid.
  • Clause 46 The composition of any one of clauses 41 to 45, which further comprises an alkali metal halide.
  • Clause 47. The composition of clause 46, wherein the alkali metal halide is sodium chloride.
  • Clause 48 The composition of any one of clauses 41 to 47, wherein the chlorite salt is selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
  • Clause 49 The composition of clause 48, wherein the chlorite salt is sodium chlorite.
  • Clause 50 The composition of any one of clauses 41 to 49, wherein the polydentate ligands are as defined in any one of clauses 15 to 21 .
  • a kit comprising, separately:
  • polydentate ligands which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms.
  • Clause 52 The kit of clause 51 , wherein the chlorite salt is as defined in clause 48 or clause 49.
  • Clause 53 The kit of clause 51 or clause 52, wherein the pKa is about 1.5 to about 3.0.
  • Clause 54 The kit according to any one of clauses 51 to 53, wherein the acid comprises a bisulfate buffer.
  • Clause 55 The kit of any one of clauses 51 to 54, which comprises an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
  • Clause 56 The kit of clause 55, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid.
  • Clause 57 The kit of any one of clauses 51 to 56, which further comprises an alkali metal halide.
  • Clause 59 The kit of any one of clauses 51 to 58, wherein the polydentate ligand is as defined in any one of clauses 15 to 21 .
  • Clause 60 The kit of any one of clauses 51 to 59, further comprising an iron or manganese salt.
  • a kit comprising, separately:
  • a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or
  • a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
  • Clause 62 The kit of clause 61 , wherein the chlorite salt is as defined in clause 48 or clause 49.
  • Clause 63 The kit of clause 61 or clause 62, wherein the pKa is about 1.5 to about 3.0.
  • Clause 64 The kit according to any one of clauses 61 to 63, wherein the acid comprises a bisulfate buffer.
  • Clause 65 The kit of any one of clauses 61 to 64, which comprises an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
  • Clause 66 The kit of clause 65, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid.
  • Clause 67 The kit of any one of clauses 61 to 66, which further comprises an alkali metal halide.
  • Clause 69 The kit of any one of clauses 61 to 68, wherein the complex is as defined in any one of clauses 12 to 21 .
  • EXPERIMENT 1 NaCIO 2 /pH 2 NaHSO 4 buffer/compound 1.
  • Table 1 shows a compilation of the results obtained at different catalyst concentrations.
  • 0.1-1 pM of compound 1 a steady built-up of chlorine dioxide was obtained.
  • Increasing to 5 or 10 pM of compound 1 leads to the formation of a much higher concentration of chlorine dioxide after 5 minutes than the reference without catalyst after 1 hr reaction time.
  • the amount of chlorine dioxide generated when using 0.1 pM, 5 pM and 10 pM of compound 1 was substantially greater when using a NaHSC buffer at a pH of 2.32 than when using an acetate buffer at a pH of 5 (compare 1.1 mM, 0.7 mM and 0.2 mM of CIO2 generated after 1 hour using 10 pM, 5 pM and 0.1 pM of 1 in an acetate buffer with 2.75 mM, 2.62 mM and 1.63 mM generated after 1 hour using 10 pM, 5 pM and 0.1 pM of 1 in a NaHSC buffer.
  • EXPERIMENT 2 NaCIC /Various NaHSC concentrations/compound 1.
  • EXPERIMENT 3 NaHSO 4 /Various NaCIC concentrations/compound 1.
  • EXPERIMENT S NaCIO 2 /pH 2 NaHSO 4 buffer/compounds 2-11.
  • a series of Mn and Fe complexes (complexes 2-11) were tested in aqueous solutions comprising 11 mM NaHSC buffer and 10 mM NaCIC>2 at pH 2.0, using complex concentrations of 1 or 10 pM.
  • the concentrations of CIO2 formed were analysed after 300 and 780 seconds.
  • the blank experiment was carried out, using 10 mM NaCIC>2 and 10 mM oxalic acid in water at pH 2.0 at 25 °C. A slow formation of chlorine dioxide was observed (absorbance of 0.17 at 359 nm after 1 hr, which is equivalent to 0.14 mM chlorine dioxide, based on the extinction coefficient of 1250 M' 1 crrr 1 (J.Am.Chem.Soc., 136, 3680-3686 (2014)).
  • Table 7 shows a compilation of the results obtained at different catalyst concentrations.
  • 0.1-1 pM of compound 1 a steady built-up of chlorine dioxide was obtained.
  • Increasing to 10 pM of compound 1 leads to the formation of a much higher concentration of chlorine dioxide after 5 minutes than the reference without catalyst after 1 hr reaction time or than when using 0.1 or 1 pM of compound 1 .
  • the amount of chlorine dioxide was somewhat lower when using 10 pM of compound 1 than when using 1 pM of compound 1.
  • the amount of chlorine dioxide generated when using 0.1 pM and 10 pM of compound 1 was substantially greater when using an oxalate buffer at a pH of 2 than when using an acetate buffer at a pH of 5 (compare 1.1 mM and 0.2 mM of CIO2 generated after 1 hour using 10 pM and 0.1 pM of 1 in an acetate buffer with 1.9 mM and 1.1 mM generated after 1 hour using 10 pM and 0.1 pM of 1 in an oxalate buffer.
  • EXPERIMENT S NaCIO 2 /NaHSO 4 /NaCI/compound 1.
  • the blank experiment was carried out using 10 mM NaCIC>2, 11 mM NaHSC and 100 mM NaCI in water at pH 2.0 at 25 °C. A significant formation of chlorine dioxide was already observed (absorbance of 0.95 at 359 nm after 1 hr, which is equivalent to 1.5 mM chlorine dioxide, based on the extinction coefficient of 1250 M' 1 cm -1 (J.Am.Chem. Soc., 136, 3680-3686 (2014)).
  • Table 8 shows a compilation of the results obtained at different catalyst concentrations.
  • the amount of chlorine dioxide generated when using 1 pM of compound 1 was substantially greater when using a NaHSC buffer at a pH of 2 in the presence of 100 mM NaCI than in the absence of NaCI (compare 4.8 mM of CIO2 generated after 1 hour using 1 pM of 1 using a NaHSC buffer at a pH of 2 in the presence of 100 mM NaCI with 2.6 mM generated after 1 hour using 1 pM of 1 using a NaHSC buffer at a pH of 2 without added NaCI.
  • EXPERIMENT S NaCIO 2 /pH 2 NaHSO 4 buffer/compound 1/NaCI
  • the experiment was carried out at 25 °C in a mixture of 11 mM NaHSC buffer, 10 mM NaCIC>2 at pH 2.0, and with 1 pM of compound 1.
  • the effect of the addition of NaCI was tested.
  • the amount of NaCI was varied between 0 and 1000 mM.
  • the concentrations of CIO2 formed were analysed after 60 minutes. A maximum of 8 mM of CIO2 can be formed when starting from 10 mM chlorite.

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Abstract

The present invention relates to a method of generating chlorine dioxide from chlorite salts in the presence of an iron or manganese ion-containing complex, compositions and kits suitable for use in such methods and a method of treating water or a substrate with such compositions.

Description

OXIDATIVE METHOD
FIELD
The present invention relates to a method of generating chlorine dioxide from chlorite salts in the presence of an iron or manganese ion-containing complex, a method of treating a substrate with a chlorine-containing oxidant in the presence of an iron or manganese ion-containing complex and related aqueous media, kits and compositions.
BACKGROUND
The function of chlorine dioxide as an oxidant is useful for a variety of applications, such as for disinfection of, and removal of manganese and iron metals via formation of their oxides from, (surface) water, treatment of industrial water, such as in cooling towers, for taste and odour control, and for the bleaching of cellulosic substrates, particularly wood pulp. Besides significant usage in these applications, chlorine dioxide is also used in food processing, such as in the washing of fruit and vegetables, cleaning of animal processing equipment and animal carcasses, and treatment of poultry and animal habitats.
Chlorine dioxide serves as a highly selective oxidant owing to a unique one- electron transfer mechanism in which it is reduced to chlorite (see Alternative Disinfectants and Oxidants Guidance Manual, United States Environmental Protection Agency, 1999 (www.epa.gov/ogwdw/mdbp/alternative_disinfectants_guidance.pdf) in particular Chapter 4 thereof (“Chlorine Dioxide”)).
Chlorine dioxide is used widely for wood pulp bleaching and water treatment, the latter especially for antimicrobial activity, because it causes gross physical damage to bacterial cells and viral capsids. The efficacy of chlorine dioxide is at least as good as that of elemental chlorine, with 2-4 log inactivation when using a few mgs/L of chlorine dioxide.
A wide variety of transition metal-based bleaching complexes have been studied to enhance the bleaching or delignification activity of hydrogen peroxide on wood pulp. For example, dinuclear manganese complexes based on triazacyclononane ligands are known to be particularly active complexes. These complexes activate hydrogen peroxide towards the bleaching of cellulosic substrates, for example wood pulp or raw cotton (see for example EP 0 458 397 A2 (Unilever NV and Unilever pic), WO 2006/125517 A1 (Unilever pic et al.), US 2001/0025695 A1 (Patt et al.), WO 2011/128649 (Unilever pic et al.), and WO 2011/141692 (Unilever pic et al.)). For a detailed review of the different classes of bleaching complexes active with hydrogen peroxide or dioxygen, reference is made to R Hage and A Lienke, Angew. Chem., Int. Ed. Engl., 45, 206-222 (2006).
It has been described (see T P Umile & J T Groves in Angew. Chem., Int. Ed. Engl., 50, 695-698 (2011), T P Umile, D Wang & J T Groves in Inorg. Chem., 50, 10353- 10362 (2011), WO 2012/027216 (The Trustees of Princeton University) and S D Hicks et al. in Angew. Chem., Int. Ed. Engl., 50, 699-702 (2011)) that manganese complexes of porphyrins and porphyrazines can catalyse the formation of chlorine dioxide from sodium chlorite (in phosphate buffer pH 6.8-7.0 or acetate buffer pH 4.5-5.1). In 2014, S D Hicks et al. ( . Am. Chem. Soc., 136, 3680-3686 (2014)) described the use of manganese complexes of the pentadentate N,N-bis(pyridin-2-ylmethyl)bis(pyridin-2- yl)methylamine (N4Py) and N-benzyl-N,N’,N’-tris(pyridin-2-ylmethyl)-1 , 2, -diaminoethane (Bn-TPEN) in the catalytic formation of chlorine dioxide from chlorite in acetate buffer pH 5.0.
Iron complexes based on N4py and two bispidone ligands ((dimethyl 2,4-di-(2- pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5- dicarboxylate and (dimethyl 2,4-di-(2-pyridyl)-7-methyl-3-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate) have been studied by P Barman et al (Inorg. Chem., 55, 10170-10181 (2016)) for their ability to accelerate the formation of chlorine dioxide from chlorite at pH 5.0 in acetate buffer. A different approach was reported by T B Champ, et al. in Inorg. Chem., 60, 2905-2910 (2021), where Mn and Fe complexes based on substituted bisphenolglycine were reacted with chlorite and peracetic acid to generate chlorine dioxide at pH 4.0.
A wide range of iron and manganese complexes are described in WO 2016/198891 A1 and WO 2016/198890 A1 (both Chemsenti Ltd.). Specific iron and manganese complexes are exemplified as accelerating chlorine dioxide production from chlorite in aqueous solutions comprising acetate buffers and having a pH of 5.0. A particular catalyst is shown to be active at high pH (up to pH 11 .0).
Although the decomposition of chlorite catalysed by iron salts into chlorine dioxide, chlorate and various other species is known (see for example I Fabian in Coord. Chem. Rev., 216-217, 449-472 (2001)), porphyrin-based iron complexes, in contrast to manganese-ion -containing analogues, have been shown to dismutate chlorite into chlorate and chloride anions without forming chlorine dioxide (see M J Zdilla et al. (Inorg. Chem., 48, 2260-2268 (2009))).
In the publications concerning manganese complexes of porphyrins, porphyrazines, N4py, Bn-TPEN, and iron complexes of pentadentate bispidon ligands, it is suggested that the use of these may result in an alternative route for the production of chlorine dioxide from chlorite, instead of using chlorate and a reducing agent. The latter process is the most common process to produce chlorine dioxide on large scale in, for example, pulp bleaching plants. For small-scale chlorine dioxide production, addition of a chemical oxidising agent (elemental chlorine, or hypochlorite + HCI) to chlorite solution, acidification of chlorite by HCI, or an electrochemical oxidation step is commonly employed.
No indication in the patents or academic literature mentioned above can be found that at low pH, chlorine dioxide formation from chlorite in the presence of a catalyst can be much higher than at the higher pH values described in the art.
It is undesirable, for reasons of safety, to produce chlorine dioxide in a chemical plant, and then store and ship it to where it is to be consumed, for example in a pulp mill or water treatment facility. Typically, therefore, chlorine dioxide is produced next to its place of use by allowing sodium chlorate to react with an acid such as sulfuric acid and a reducing agent (such as hydrogen peroxide, sulfur dioxide or methanol). In pulp treatment, for example, the resultant gaseous chlorine dioxide is then brought to another vessel, trapped in water and used as such to the treat the pulp slurry.
Additional methods are known that produce chlorine dioxide from chlorite, either via acidification with hydrochloric acid or sulfuric acid, via oxidation of chlorite using chlorine, for example, or via electrochemical methods. Such processes are often used for small scale production of chlorine dioxide (for example in small units to deliver chlorine dioxide for hygiene/antimicrobial applications).
Although chlorine dioxide is of great benefit and is used in a variety of applications, it would be of benefit to the art to improve and/or develop alternative methods of producing this chemical from chlorite salts in acidic media. This invention addresses that need.
SUMMARY
Under acidic conditions (such as solutions of about pH 1 to about pH 3.5), those skilled in the art would expect irreversible degradation of manganese or iron complexes to take place owing to an increased probability of protonation of the chelating atoms of the stabilising ligands, preventing these ligands from binding to and stabilising the manganese or iron ions. However, the inventors have found that iron and manganese complexes comprising a variety of polydentate nitrogen donor ligands are surprisingly active in accelerating the formation of chlorine dioxide from chlorite salts in acidic solutions comprising bisulfate or oxalate buffers.
Viewed from a first aspect, therefore, the invention provides a method of generating chlorine dioxide from a chlorite salt, comprising contacting, in an aqueous medium:
(i) the chlorite salt; and
(ii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion, through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms, wherein the aqueous medium comprises a bisulfate or oxalate buffer, and the aqueous medium has a pH of about 1 to about 3.5.
Viewed from a second aspect, the invention provides a composition comprising:
(i) an aqueous medium comprising a bisulfate or oxalate buffer, and having a pH of about 1 to about 3.5;
(ii) a chlorite salt; and
(iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
Viewed from a third aspect, the invention provides a method of treating water or a substrate comprising contacting the water or the substrate with the composition defined in the second aspect.
Viewed from a fourth aspect, the invention provides a solid composition comprising:
(i) a solid acid comprising bisulfate or oxalate and having a pKa in water at 25°C of about 1 to about 3.5;
(ii) a chlorite salt; and (iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
Viewed from a fifth aspect, the invention provides a composition comprising a chlorite salt, an acid comprising bisulfate or oxalate, and having a pKa in water at 25°C of about 1 to about 3.5 and one or more polydentate ligands, which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms. In some embodiments, the one or more polydentate ligands are not porphyrin or porphyrazine ligands.
Viewed from a sixth aspect, the invention provides a kit comprising, as separate components:
(i) a chlorite salt;
(ii) an acid comprising bisulfate or oxalate and having a pKa in water at 25°C of about 1 to about 3.5; and
(iii) one or more polydentate ligands, which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms.
Viewed from a seventh aspect, the invention provides a kit comprising, separately:
(i) a chlorite salt;
(ii) an acid comprising bisulfate or oxalate and having a pKa in water at 25°C of about 1 to about 3.5; and either:
(iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or
(iv) a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
The use of chlorite salts according to the present invention in the context of wood pulp bleaching and/or delignification, involving use of the iron or manganese ioncontaining complexes described herein in acidic conditions, allows better and/or more flexible use of these chemicals, and offers an alternative to existing methods. The invention is, however, not limited to the treatment of wood pulp. Other substrates, including cellulosic substrates such as raw cotton or stained cotton garments, may be treated in accordance with this invention, for example with detergent or other formulations comprising chlorite salts and the complexes or polydentate ligands described herein. Such formulations may be used in cleaning and hygiene methods in lieu of formulations containing more traditional peroxy-based bleaches. As is discussed in more detail below, the invention is also of use in the treatment of water, for example to ameliorate microbial contamination, and other applications in which the antimicrobial effect of chlorine dioxide is of benefit.
Moreover, the invention permits alteration, e.g. improvement, of existing uses of chlorite salts in acidic conditions, for example so as to allow a reduction in the temperature at which, or the duration for which, these chemicals are used. Furthermore, smaller dosages of chlorite salts may be used than are used in the absence of the iron or manganese complexes described herein, for example so as to obtain antimicrobial activity. Another advantage of the invention is that, for example, solid chlorite salts in conjunction with an iron or manganese complex and an acid can be used for the antimicrobial applications, without needing to generate chlorine dioxide off line (i.e. ex situ).
The invention thus permits alteration, e.g. improvement, of existing formation of chlorine dioxide from chlorite in acidic media.
Further aspects and embodiments of the invention will be evident from the discussion that follows below.
DETAILED DESCRIPTION
As summarised above, the present invention is based on the finding that complexes comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion, through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands, or complexes comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion, through at least three nitrogen atoms, can accelerate the conversion of chlorite to chlorine dioxide in acidic solutions having a pH of about 1 to about 3.5 and buffered by bisulfate or oxalate buffers, and thereby offer improvements or an alternative to existing methods and compositions used for the generation of chlorine dioxide from chlorite.
The methods of the first and third aspects of the invention involve use of, and the composition of the second aspect of the invention comprises, an aqueous medium with a pH of about 1 to about 3.5, which will generally have at least 1 wt% water, by which is meant that the water-containing liquid constituting the liquid aqueous medium comprises at least 1 % by weight water, more typically at least 10 wt%, even more typically 25 wt%, and most typically at least 50 wt% water. Typically the aqueous medium will be a solution (i.e. in which its various components, such as chlorite salt(s), acid and the iron or manganese complex are dissolved). Although less typical, other aqueous (i.e. watercontaining) media, including slurries and suspensions, may also be used as the aqueous medium. The aqueous medium comprises a liquid continuous phase, the liquid component of which is predominantly, i.e. between 50 and 100 wt% water, typically between 80 and 100 wt% water. Dependent on the use to which the aqueous medium referred to herein is being or is intended to be put, the liquid balance (if any) of the aqueous medium that is not water may be any convenient liquid, for example a liquid alcohol, e.g. a C1.4 alcohol such as methanol or ethanol. Where present, additional liquids will typically be water-miscible. Although the liquid continuous phase will often be entirely water, it will be understood that this does not exclude the presence of small amounts of other liquids (e.g. in a total amount of less than about 10 wt%, more typically less than about 5 wt%), e.g. as contaminants in the other materials with which the liquid continuous phases are brought into contact.
The liquid of the aqueous media described herein has a pH of about 1 to about 3.5. According to some embodiments, the pH is about 1.5 to about 3.0, such as about 2 to about 2.5. Solutions or other systems having this pH may be readily prepared by the skilled person. For example, as the skilled person will recognise, appropriate buffers will allow control over the pH to be achieved and selection of appropriate buffers (in addition to bisulfate and/or oxalate buffers) is within the normal ability of those of normal skill. Bringing the pH of the aqueous media to the desired value may be achieved by addition of appropriate amounts of an acid. This may be a solid acid, such as one having a pKa in water at 25°C of about 1 to about 3.5. The aqueous medium comprises a bisulfate or oxalate buffer which may be present by addition of, for example, sodium bisulfate, potassium bisulfate, or oxalic acid. Alternatively, the acid may first be dissolved in an appropriate amount of water or another suitable liquid, and the resultant composition may then be added to a composition comprising the chlorite salt and the iron or manganese complex. Alternatively, a liquid form of an acid may be added to a composition comprising the chlorite salt and the iron or manganese complex. The acid can be either used as obtained from a chemical supplier or it can be diluted in an aqueous medium prior to use. The pH of the aqueous medium comprising the iron or manganese complex, chlorite salt and acid may be determined immediately after mixing the components. As chlorine dioxide is generated from the chlorite salt, the pH of the aqueous medium may increase above 3.
Suitable acids include those with pKa values of about 3.5 or lower. For the avoidance of doubt, pKa values herein relate to determinations conducted in water, at 25°C, for the reaction AH H+ + A; wherein AH denotes the acid and A' denotes the conjugate base, as described in the CRC Handbook of Chemistry and Physics, 91st edition, 2010, Dissociation Constants of Organic Acids and Bases, and Dissociation Constants of Inorganic Acids and Bases, and the references cited therein. Accordingly, where the acid used is a bisulfate ([HSO4]'), for example, the conjugate base, A; is sulfate ([SO4]2'); where the acid used is hydrochloric (HCI), for example, the conjugate base is chloride (Cl"). For further avoidance of doubt, the pKa of water at25°C is defined herein, as is generally recognised in the art, as being 14.0.
Suitable acids include sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid. For the avoidance of doubt, the aqueous medium may comprise a bisulfate or oxalate buffer, which may be provided by the addition of sodium bisulfate, potassium bisulfate, or oxalic acid, and also comprise a further acid, such as sulphuric acid, hydrochloric acid and/or hydrobromic acid.
In some embodiments, the aqueous medium comprises a bisulfate buffer. In some embodiments, the aqueous medium comprises one or more acids selected from sodium bisulfate, potassium bisulfate and hydrochloric acid. Typically, the aqueous medium comprises one of such acids. In some embodiments, the aqueous medium comprises an acid selected from sodium bisulfate and potassium bisulfate, and further comprises hydrochloric acid.
The chlorite salt used in accordance with the various aspects of the invention is typically an inorganic chlorite salt, the nature of which is not critical to the operation of the invention. One or more chlorite salts may be used in any given method although typically only one chlorite salt will be used. Non-limiting examples of chlorite salts that may be used include sodium chlorite (NaCIO2), potassium chlorite (KCIO2), lithium chlorite (l_iCIO2), calcium chlorite (Ca(CIO2)2), barium chlorite (Ba(CIO2)2) and magnesium chlorite (Mg(CIC>2)2). Typically, sodium chlorite or potassium chlorite is used. More typically, the chlorite salt used is sodium chlorite.
As described above, the method according to the first aspect of the invention comprises contacting, in an aqueous medium with a pH of about 1 to about 3.5, a chlorite salt and a complex comprising one or more iron or manganese ions (which complexes are interchangeably referred to herein as iron or manganese complexes) and one or more polydentate ligands (as defined herein). It will be understood that contacting may be achieved in a variety of ways. For example, an aqueous medium may be prepared, to which chlorite salt and metal complex are added, separately or in combination. The chlorite salt may be added as a solid, for example as a powder or granulate, or as an optionally buffered solution in water. Likewise, the metal complex may be added as a solid, for example as a powder, crystal granulate, either on its own or, for example diluted with a salt. Alternatively, it may be added as an optionally buffered solution in water, or as a solution in an alternative solvent such as an alcohol. Where added as a solution, the solution is typically formed by dissolving the iron or manganese complex in (optionally buffered) water. Typically, the chlorite salt is dissolved in an aqueous liquid followed by the addition of an acid, to achieve the desired pH value. The iron or manganese complex can be added as a solid or solution at any stage, but will be typically be added to the aqueous medium already comprising the chlorite salt and/or the acid.
Further permutations are also possible and may be easily envisaged by the skilled person. For example, the iron or manganese complex may not be added as such: iron or manganese ions may be present in, or may be added to, an aqueous liquid and an iron or manganese complex formed in situ by addition of an appropriate ligand. For example, untreated tap water may comprise sufficient quantities of iron or manganese ions that useful quantities of the iron or manganese complexes described herein can be generated in situ by addition of an appropriate amount of the polydentate ligands described herein.
Alternatively, in accordance with the fifth and sixth aspects of the invention, a composition or kit comprising a polydentate ligand as defined herein, a chlorite salt and an acid comprising bisulfate or oxalate, and having a pKa in water at 25°C of about 1 to about 3.5 may be provided from which the composition in accordance with the second aspect of the invention may be prepared. Although the polydentate ligand in the composition of the second aspect is part of an iron or manganese complex, it will be understood from the previous paragraph that it is not necessary that the composition is prepared by introduction of an iron or manganese complex as such, since the iron or manganese complex may be made in situ by provision of an appropriate source of iron or manganese ions. For the avoidance of doubt, the polydentate ligand of the kit may initially be reacted with an iron or manganese salt to form the corresponding iron or manganese complex, which may (or may not) be isolated before being contacted with the chlorite salt and polydentate ligand described herein.
For the avoidance of doubt, where an acid is described to comprise bisulfate or oxalate, the acid includes these species either as anions, with the charge stabilised by one or more counterions, or as uncharged species bonded to one or more other moieties, such as hydrogen atoms. For example, as defined herein, bisulfate is a component within sodium bisulfate and potassium bisulfate, and oxalate is a component within oxalic acid.
Alternatively, in accordance with the fourth aspect of the invention, a solid composition comprising a solid acid comprising bisulfate or oxalate, and having a pKa in water at 25°C of about 1 to about 3.5, a chlorite salt and an iron or manganese complex may be provided, which may be combined with an aqueous solution to provide the composition of the second aspect. Similarly, and in accordance with the seventh aspect, a kit comprising a chlorite salt, an acid comprising bisulfate or oxalate, which may be a solid acid, and which has a pKa in water at 25°C of about 1 to about 3.5 and an iron or manganese complex may be provided, which may be combined with an aqueous solution to provide the composition of the second aspect.
Where the acid is a solid acid, it may be selected from sodium bisulfate, potassium bisulfate and oxalic acid. The chlorite salt may be as defined above, and is preferably sodium chlorite.
The weight ratio of solid acid to chlorite salt and to iron or manganese complex depends on the desired concentrations of each component when combined with, e.g. dissolved into, an aqueous solution. Typically, the amount of the iron or manganese complex is much lower than that of the solid acid or chlorite salt, which can make precise dosing more difficult. Often, the iron or manganese complex is ‘diluted’ with a filler, for example in a granulated form, so the dosage of the complex is easier to achieve. Suitable fillers include sodium sulfate, sodium chloride, potassium chloride, potassium sulfate, magnesium sulfate, and calcium sulfate. Granulated materials comprise granule particles, which are asymmetrical aggregates of powder particles. Granulation methods are widely known in the art (see, for example, Shanmugam, Bioimpacts, 2015, 5(1), 55- 63). Granule materials can be produced by means of moist granulation, dry granulation, or compaction, and by means of melt-solidification granulation. Granulation of the solid composition may improve the storage stability of the iron or manganese complex. This approach to granulate iron or manganese complexes is well known in detergent formulations, especially in laundry detergents and automatic dishwash detergents. Non limiting examples include W095/06710 (Unilever N.V.), WO94/21777 (Unilever N.V.), WO2017/153528 (Conopco INC., Unilever), WO2010/115582 (Clariant International Ltd.), WO2014/198368 (Weylchem Wiesbaden GmbH), WO2018/210442 (Weylchem Wiesbaden GmbH), EP1913124B (Clariant, Produkte GmbH), and WO2011/005827 (Procter and Gamble Company).
Compositions in accordance with the fifth aspect of the invention may be added to a liquid medium to form a composition in accordance with the second aspect of the invention, which may be used in accordance with the first aspect of the invention.
Analogously, it will be understood that kits in accordance with the sixth or seventh aspect of the invention may likewise be used to form a composition in accordance with the second aspect of the invention, which may be used in accordance with the first aspect of the invention.
According to particular embodiments, the kit of the invention may take the form of a cartridge comprising separated compartments, for example of the type described in WO 2012/027216 A1 (supra), comprising the components of the kit, i.e. the chlorite salt, the acid and the polydentate ligand or iron or manganese complex. For instance, in particular embodiments, the iron or manganese complex may be adsorbed (immobilised) on a solid support, permitting generation of chlorine dioxide by allowing water to flow through the cartridge. Advantageously, it will be understood that, where iron or manganese complexes are immobilised in such systems, these may be reused upon replacement of the chlorite salt.
Irrespective of how the aqueous media of the various aspects of the invention are prepared, the one or more chlorite salts in it are typically present at a concentration of about 0.01 to about 100 mM, for example about 1 to about 50 mM. It will of course be recognised that the skilled person will be able to employ an appropriate concentration of chlorite salt, as with concentrations/amounts of other components described herein, without undue burden.
In some embodiments, the aqueous media of the various aspects of the invention comprise an alkali metal halide. The inventors have found that the presence of alkali metal halides, such as sodium chloride, in the aqueous media together with an iron or manganese complex as defined herein unexpectedly further accelerates the generation of chlorine dioxide from the chlorite salt. The alkali metal halide may comprise any alkali metal or halide. Typically, however, the alkali metal is selected from sodium, potassium and lithium, most typically sodium and potassium. The halide may be any of chloride, fluoride, bromide or iodide. Typically, the halide is chloride. Mixtures of different alkali metal halides may be present within the aqueous media. Typically, however, the alkali metal halide is sodium chloride.
The aqueous medium may comprise about 10 mM to about 6 M of the alkali metal halide. For example, the aqueous medium may comprise about 15 mM to about 5 M, about 20 mM to about 4 M, about 25 mM to about 3 M, about 30 mM to about 2 M, about 35 mM to about 1 M, about 40 mM to about 0.8 M, or about 50 mM to about 0.6 M of the alkali metal halide. Typically, the aqueous medium comprises about 100 mM to about 1 M, of alkali metal halide, such as about 100 mM to about 1 M of sodium chloride.
According to particular embodiments, the complex comprises one or more iron ions.
By a chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is meant a polydentate ligand capable of chelating one or more iron or manganese ions by the formation of coordinate bonds between three or more nitrogen atoms of the chelant and a common iron or manganese ion, chelation in this context and as the term is customarily used in the art requiring that the nitrogen atoms of the chelant coordinate to the same transition metal ion, in this case an iron or manganese ion. The chelants are thus at least tridentate. When bound to one iron or manganese ion, the chelant can be tridentate, tetradentate, pentadentate, hexadentate, heptadentate, or octadentate, with tridentate, tetradentate, pentadentate, hexadentate being most common. Further, some of the chelants described herein having a denticity of greater than six, for example eight, with octadentate ligands being capable of coordinating through eight nitrogen atoms. With these chelants, however, chelation is then often achieved by the formation of coordinate bonds between four nitrogen atoms and a common iron or manganese ion: for example four of the eight nitrogen atoms in these octadentate chelants can chelate to a first iron or manganese ion and four of these nitrogen atoms can chelate to a second iron or manganese ion. This is generally achieved by such octadentate ligands having two portions of their structure giving rise to two separate regions of chelation, often separated by a bridge, as is explained and exemplified in greater detail below with reference to specific polydentate ligands useful in accordance with the present invention.
Often, the chelants of the invention capable of chelating at least one iron or manganese ion through at least three nitrogen atoms are chelants capable of chelating at least one iron or manganese ion through four, five or six nitrogen atoms. For the avoidance of doubt, whilst a chelant capable of chelating at least one iron or manganese ion through four nitrogen atoms may have a denticity of greater than four, such a chelant does not permit chelation through five (or more) or three (or fewer) nitrogen atoms. Similarly, for example, a chelant capable of chelating at least one iron or manganese ion through three nitrogen atoms may have a denticity of greater than three, such a chelant does not permit chelation through four (or more) or two (or fewer) nitrogen atoms and so on.
It will be understood that the denticity (and thus the terms tridentate, tetradentate, pentadentate or hexadentate, heptadentate, or octadentate) refers to the number of metal ion-binding donor atoms that can bind to a metal ion. A chelant which is, for example, a tetradentate nitrogen donor thus refers to an organic molecule comprising four nitrogen atoms with lone pairs, which can bind to a common transition metal ion, which according to the present invention is an iron ion. These nitrogen donor atoms may be either aliphatic, either tertiary, secondary or primary amines, or may belong to a heteroaromatic ring, for example pyridine.
According to particular embodiments, the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formula (I) or (I- B): wherein: each D is independently selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1 - yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl and thiazol-2-yl, each of which may be optionally substituted by one or more groups independently selected from the group consisting of -F, -Cl, -Br, -OH, -OCi-C4alkyl, -NH-CO-H, -NH-CO-Ci-C4alkyl, -NH2, -NH-Ci-C4alkyl, and -Ci-C4alkyl; the or each R1 and R2 are independently selected from the group consisting of Ci-C24alkyl, Ce-warylCi-Cealkyl, Ce-waryl, Cs-CwheteroarylCi-Cealkyl, each of which may be optionally substituted by one or more groups selected from -F, -Cl, -Br, -OH, - OCi-C4alkyl, -NH-CO-H, -NH-CO-Ci-C4alkyl, -NH2, -NH-Ci-C4alkyl and -SCi-C4alkyl; and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci.44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci.2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more C i.2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci.2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci.2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci.2oalkyl groups;
R3 and R4 are independently selected from hydrogen, Ci-Csalkyl, Ci-Csalkyl-O- Ci-Csalkyl, Ce-CwaryloxyCi-Csalkyl, Ce-C aryl, Ci-Cshydroxyalkyl, Ce-CwarylCi-Cealkyl and Cs-C heteroarylCi-Cealkyl, and -(CH2)o-4C(0)OR5 wherein R5 is independently selected from: hydrogen, Ci-Csalkyl and Ce- aryl;
Q2 represents a bridge selected from the group consisting of a Ciwalkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ciwalkylene units and one Ce-warylene unit, which bridge is optionally substituted one or more times with independently selected Ci.24alkyl groups and OH groups; and
X is selected from C=O, -[C(R6)2]o-3- wherein each R6 is independently selected from hydrogen, hydroxyl, Ci-C4alkoxy and Ci-C4alkyl.
In some embodiments, in particular when the complex is a manganese complex, the or each R1 and R2 are independently selected from the group consisting of Ci- C24alkyl, Ce-warylCi-Cealkyl, Ce-waryl, Cs-CwheteroarylCi-Cealkyl, each of which may be optionally substituted by one or more groups selected from -F, -Cl, -Br, -OH, - OCi-C4alkyl, -NH-CO-H, -NH-CO-Ci-C4alkyl, -NH2, -NH-Ci-C4alkyl and -SCi-C4alkyl. Such ligands (i.e. of formula (I) and (l-B)) are known in the art as bispidons. The following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of bispidons:
• each D group is either unsubstituted or substituted with one or more, often one, Ci-C4alkyl groups;
• each D group is the same;
• each D group is an optionally substituted pyridin-2-yl;
• each D group is unsubstituted pyridin-2-yl group;
• Q2 is selected from -CH2CH2-, -CH2CH2CH2- and -CH2CHOHCH2-, each of which is optionally Ci-Cealkyl-substituted, with the bridge typically being unsubstituted;
• each R1 and R2 group is independently selected from Ci-C24alkyl, Ce-Cwaryl,
Ce- arylCi-Cealkyl, Cs-C heteroarylCH2 and CH2CH2N(R10)(R11), whereby -N(R10)(R11) is selected from -NMe2, -NEt2, -N(i-Pr)2,
• in case any R1 or R2 group is independently a Ci-C24alkyl, a Ce-C aryl, or a Ce-warylCi-Cealkyl group, it is more typically independently selected from Ci- C alkyl and Ce-C arylCi-Cealkyl, and even more typically independently selected from: Ci-Csalkyl and Ce-C arylCH2;
• particularly where the complex is a manganese complex, each R1 and R2 group is independently selected from Ci-C24alkyl and Ce-C arylCi-Cwalkyl, more typically independently selected from Ci-C alkyl and Ce-CwarylCi-Cealkyl, and even more typically independently selected from: Ci-Csalkyl and Ce-C arylCH2;
• in case any R1 or R2 is independently a Cs-C heteroarylCH2 group, it is preferably selected from pyridin-2-ylmethyl, pyrazin-2-ylmethyl, quinolin- 2-ylmethyl, pyrazol-1-ylmethyl, pyrazol-3-ylmethyl, pyrrol-2-ylmethyl, imidazol-2- ylmethyl, imidazol-4-ylmethyl, benzimidazol-2-ylmethyl, pyrimidin-2-ylmethyl, 1 ,2,3-triazol-1 -ylmethyl, 1,2,3-triazol-2-ylmethyl, 1 ,2,3-triazol-4-ylmethyl, 1,2,4- triazol-3-ylmethyl, 1 ,2,4-triazol-1-ylmethyl and thiazol-2-ylmethyl, with pyridin-2- ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, and thiazol-2-ylmethyl being more typical;
• often one of the R1 and R2 groups is Ci-C24alkyl or Ce-warylCi-Cealkyl, whilst the other of the R1 and R2 groups is a Cs-C heteroarylCH2 group or CH2CH2N(R10)(R11), whereby -N(R10)(R11) is selected from -NMe2, -NEt2, -
• one of the R1 and R2 groups is most typically Ci-C alkyl, with Ci -Ci 2alkyl more preferred, Ci-Csalkyl even more preferred and with CH3 being most preferred; and the other R1 or R2 group typically an optionally substituted pyridin-2- ylmethyl, with unsubstituted pyridin-2-ylmethyl being most typical, or is selected from CH2CH2N(R10)(R11), whereby -N(R10)(R11) is selected from -NMe2, -NEt2, - N(i-Pr)2,
• R1 is the same as R2 (for formula (I)) or each R1 is the same (for formula (II)), often methyl or pyridin-2-ylmethyl;
• groups R3 and R4 are the same.
According to specific embodiments, the bispidon is one of the following ligands: dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate (N2py3o-C1), dimethyl 2,4-di-(2-pyridyl)-3- (pyridin-2-ylmethyl)-7-methyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate (N2py3u-C1), and the iron complexes thereof (FeN2py3o-C1 , FeN2py3u-C1) which are described in WO 02/48301. Another particular preferred bispidon is dimethyl 9,9- dihydroxy-3-methyl-2,4-di-(2-pyridyl)-7-(1-(N,N-dimethylamine)-eth-2-yl)-3,7-diaza- bicyclo[3.3.1]nonane-1 ,5-dicarboxylate and the iron complex thereof as described in WO 03/104234. Other preferred bispidons are those that have instead of having R1 = methyl, other N-alkyl groups are present, for example isobutyl, (n-hexyl) C6, (n-octyl) C8, (n- dodecyl) C12, (n-tetradecyl) C14, (n-octadecyl) C18. Similarly the analogous 3-pyridin- 2ylmethyl)-7-alkyl isomeric ligands and their iron complexes thereof are preferred. Examples of such bispidons are described in WO 02/48301 , WO 03/104379 and WO 2005/049778. Also preferred tetradentate bispidons, in particular, dimethyl 2,4-di-(2- pyridyl)-3,7-dimethyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate (N2py2), dimethyl 2,4-di-(2-pyridyl)-3,7-dibutyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5- dicarboxylate; dimethyl 2,4-di-(2-pyridyl)-3,7-dioctyl-3,7-diaza-bicyclo[3.3.1]nonan-9- one-1 ,5-dicarboxylate; and dimethyl 2,4-di-(2-pyridyl)-3,7-dibenzyl-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate. Manganese and iron complexes with the tetradentate bispidons are known in literature. N2py2 and various manganese complexes made with this ligand have been described by P. Comba et al. (J. Chem. Soc., Dalton Trans, 3997-4002 (1998)). Various [Fe(N2py2)X2] complexes with X= e.g. thiocyanate and acetate are known to the skilled person (see for example P. Comba and co-workers, Inorg. Chim. Acta, 337, 407-419 (2002)). According to further embodiments, the chelant capable of chelating at least one iron ion or manganese through nitrogen atoms is of formulae (II) and (ll-B):
(II) (H-B) wherein: each Q is independently selected from -CR4R5CR6R7- and -CR4R5CR6R7CR8R9-;
R4, R5, R6, R7, R8, and R9 are independently selected from: H, Ci-C4alkyl and hydroxyCi-C4alkyl; each R1 , R2, and R3 is independently selected from the group consisting of hydrogen, Ci-C24alkyl, CH2CH2OH, CH2COOH, CH2PO3H2, Cs-C heteroarylCi-Cealkyl and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and
Q2 is a bridge selected from the group consisting of a Ci. ealkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ci-salkylene units and one Ce- arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups. In some embodiments, in particular when the complex is a manganese complex: each R1 is independently selected from the group consisting of pyridin-2- ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, benzimidazol-2-ylmethyl, pyrazin-2- ylmethyl, pyrazol-1-ylmethyl, pyrazol-3-ylmethyl, 1 ,2,3-triazol-1 -ylmethyl, 1 ,2,3-triazol-2- ylmethyl, 1 ,2,3-triazol-4-ylmethyl, 1 ,2,4-triazol-1-ylmethyl, 1 ,2,4-triazol-3-ylmethyl, thiazol-2-ylmethyl and CH2CH2N(R10)(R11); each R2 is independently selected from: hydrogen, Ci-C24alkyl, CH2CH2OH, CH2COOH and CH2PO3H2; and
R3 is selected from the group consisting of H, Ci-24alkyl, CH2CH2OH, CH2COOH and CH2PO3H2.
The following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of the ligands of formulae (I I) and (ll-B):
• where a ligand is of formula (ll-B), the ligand is symmetrical, i.e. each R1 is the same and each R2 is the same; and each Q group at the same position (e.g. between the bridging moiety-bearing and R2-substituted nitrogen atoms) in each ring is the same;
• each Q is the same, for example each Q is -CR4R5CR6R7-, in which R4, R5, R6 and R7 are often H, which limitation defines the class of ligands often known as 1 ,4,7-triazacyclononane ligands;
• if any of R1 , R2, and/or R3 is a Cs-C heteroarylCi-Cealkyl group, such groups are selected from pyridin-2-ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, benzimidazol-2-ylmethyl, pyrazin-2-ylmethyl, 1 ,2,4-triazol-3-ylmethyl, 1 ,2,4- triazol-1 -ylmethyl, thiazol-2-ylmethyl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3- triazol-4-yl, pyrazol-3-ylmethyl and pyrazol-1 -ylmethyl,;
• R1 , R2, and/or R3 are often independently Ci-C24alkyl, pyridin-2-ylmethyl, or quinolin-2-ylmethyl.
• if R1 , R2, and/or R3 is a heteroaryl methyl group this will often be pyridin-2- ylmethyl;
• particularly where the complex is a manganese complex, R1 is often pyridin-2- ylmethyl or quinolin-2-ylmethyl, often pyridin-2-ylmethyl;
• -R1 , -R2, and/or -R3 (such as, and in particular when the complex is a manganese complex, R1) is -CH2CH2N(R10)(R11) in which any R10 and/or R11 moiety referred to as being optionally substituted with one or more Ci.2oalkyl groups is typically either unsubstituted or only substituted with one Ci-2oalkyl group;
• where R1 , R2, and/or R3 (such as, and in particular when the complex is a manganese complex, R1) is CH2CH2N(R10R11), non-limiting examples of such groups include: di(p-methylbenzyl)amino, as an example of a di(C6-ioarylCi. 4alkyl)amino; pyrrolidinyl, piperidinyl or morpholinyl, as examples of NR7; di(piperidinylethyl)amino, as an example of di(heterocycloalkylCi-6alkyl)amino; and di(pyridin-2-ylethyl)amino, as an example of a di(heteroarylCi-6alkyl)amino.
• if present, each -N(R10)(R11) is independently selected from the group consisting of -NMe2, -NEt2, -N(/-Pr)2,
• if R1 , R2 and/or R3 (such as, and in particular when the complex is a manganese complex, R2) is Ci-C24alkyl, this is a Ci-Cealkyl, and often methyl;
• particularly where the complex is a manganese complex, R3 is Ci-C24alkyl, more typically a Ci-Cealkyl, and often methyl and is typically the same as R2;
• for ligands of formula (I l-B), bridge Q2 is typically Ci-ealkylene, often ethylene or n-propylene, and most often ethylene.
According to particular embodiments of the invention, ligands of formula (II) or (II- B) are selected from the group consisting of 1 ,4,7-trimethyl-1 ,4,7-triazacyclononane (Mes-TACN), 1 ,2-bis(4,7-dimethyl-1 ,4,7-triazacyclonon-1-yl)-ethane (Me4-DTNE), 1- (pyridin-2-ylmethyl)-4,7-dimethyl-1 ,4,7-triazacyclononane, 1 ,4-bis(pyridin-2-ylmethyl)-7- methyl-1 ,4,7-triazacyclononane, 1 ,4, 7-tris(pyridin-2-ylmethyl)- 1 ,4,7-triazacyclononane, 1 ,2-bis(4-methyl-7-pyridin-2-yl-1 ,4,7-triazacyclonon-1-yl)-ethane, 1 ,3-bis(4-methyl-7- pyridin-2-yl-1 ,4,7-triazacyclonon-1-yl)-propane, 1-ethyl-4,7-bis(quinolin-2-ylmethyl)- 1 ,4,7-triazacyclononane, and 1-methyl-4,7-bis(quinolin-2-ylmethyl)-1 ,4,7- triazacyclononane. According to particular embodiments, ligands of formula (II) are selected from 1-(pyridin-2-ylmethyl)-4,7-dimethyl-1 ,4,7-triazacyclononane and 1 ,4- bis(pyridin-2-ylmethyl)-7-methyl-1 ,4,7-triazacyclononane.
According to particular embodiments of the invention, particularly when the complex is a manganese complex, ligands of formula (II) are selected from the group consisting of 1 ,4,7-trimethyl-1 ,4,7-triazacyclononane, 1-(pyridin-2-ylmethyl)-4,7- dimethyl-1 ,4,7-triazacyclononane, 1 ,2-bis(4-methyl-7-pyridin-2-yl-1 ,4,7-triazacyclonon- 1-yl)-ethane and 1 ,3-bis(4-methyl-7-pyridin-2-yl-1 ,4,7-triazacyclonon-1-yl)-propane. According to even more particular embodiments, the ligand of formula (I I) is 1 ,4,7- trimethyl-1 ,4,7-triazacyclononane or 1-(pyridin-2-ylmethyl)-4,7-dimethyl-1 ,4,7- triazacyclononane.
According to further embodiments, the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formulae (III) or (IV):
(HI) (IV) wherein: each -Q- is independently selected from -N(R)C(RI)(R2)C(RS)(R4)- and -N(R)C(RI)(R2)C(R3)(R4)C(R5)(R6)-; each -Q1- is independently selected from -N(R’)C(RI)(R2)C(R3)(R4)- and -N(R’)C(RI)(R2)C(R3)(R4)C(R5)(R6)-; each R is independently selected from: hydrogen; the group consisting of Ci- C2oalkyl, C2-C2oalkenyl, C2-C2oalkynyl, Ce-C aryl and C7-C2oarylalkyl, each of which may be optionally substituted with Ci-Cealkyl and/or Cs-Cwheteroaryl; and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more C i-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci.2oalkyl groups; the two -R’ groups of the two Q1 groups together form bridging moiety -Q2-;
Q2 is a bridge selected from the group consisting of a C2-6alkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce-C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups; and
Ri-Re are each independently selected from: H, Ci-4alkyl and hydroxyCi.4alkyl. In some embodiments, in particular when the complex is a manganese complex, each R is independently hydrogen or is selected from the group consisting of Ci-C2oalkyl, C2-C2oalkenyl, C2-C2oalkynyl, Ce-Cwaryl and C?-C2oarylalkyl, each of which may be optionally substituted with Ci-Cealkyl.
The following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of the ligands of formulae (III) and (IV):
• Q2, which may be present in chelants of formula (III), is an ethylene or n- propylene bridge;
• each -Q- is independently selected from -N(R)(CH2)2- and -N(R)(CH2)s-;
• each -Q1- is independently selected from -N(R’)(CH2)2- and -N(R’)(CH2)s-;
• each R is each selected from: hydrogen, Ci-C2oalkyl, Ce-C aryl, C?-C2oarylalkyl, pyridin-2-ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, benzimidazol-2- ylmethyl, more typically hydrogen, methyl, ethyl, benzyl, or pyridin-2-ylmethyl, yet more typically hydrogen, methyl, or benzyl;
• particularly where the complex is a manganese complex, each R is selected from: hydrogen, Ci-C2oalkyl and Ce-Cwaryl, more typically hydrogen, a Ci-C2oalkyl group, a Ce-Cwaryl group or a C?-C2oarylalkyl group, more typically still hydrogen, methyl, ethyl, or benzyl;
• Ri-Re are each typically hydrogen or Ci-4alkyl, more typically still hydrogen or methyl, for example hydrogen;
• particularly where the complex is a manganese complex, groups having the same descriptor, e.g. R, Ri, Q1 etc, are typically the same;
• the ligand is of formula (lll-A), i.e. a cross-bridged tetraaza-1 ,4,8,11- cyclotetradecane ligand: wherein R is as defined for formulae (III) and (IV) above, including the particular embodiments immediately hereinbefore described. Typically, each R in formula (lll-A) is independently selected from the group consisting of methyl, ethyl and benzyl. Typically, each R is the same, often methyl. Other suitable cross-bridged ligands (so-called because of the presence of a bridge linking two non-adjacent nitrogen atoms of the tetrazacycloalkane) are described in in WO 98/39098 A1 (The University of Kansas). In some embodiments, the ligand of formula (III) or formula (lll-A) is 4,11-dimethyl-1 ,4,8,11-tetraazabicyclo[6.6.2]hexadecane.
Typical ligands of formula (IV) are tetraaza-1 ,4,7,10-cyclododecane and tetraaza-1 , 4, 8, 11 -cyclotetradecane, in either of which each of the hydrogen atoms attached to the four nitrogen atoms may be independently substituted for a Ci-C2oalkyl, Ce-Cioaryl or a C7-C2oarylalkyl group. According to particular embodiments, ligands of formula (IV) may be tetraaza-1 , 4, 7, 10-cyclododecane-based and tetraaza-1 , 4, 8, 11- cyclotetradecane-based ligands of formula (IV) wherein each R group is hydrogen, Ci- 2oalkyl, or heteroarylmethyl. Within these ligands, R is typically hydrogen, methyl, or pyridin-2ylmethyl. According to particular embodiments, ligands of formula (IV) include
1.4.7.10-tetraazacyclododecane, 1 ,4,7,10-tetramethyl-1 ,4,7,10-tetraazacyclododecane,
1.4.7.10-tetrakis(pyridin-2ylmethyl)-1 ,4,7,10-tetraazacyclododecane, 1-methyl-4,7,10- tri s (py ri d i n-2y I m ethy I)- 1 ,4,7,10-tetraazacyclododecane, 1 ,4-dimethyl-7, 10-bi s(py rid i n- 2ylmethyl)-1 ,4,7,10-tetraazacyclododecane, 1 ,4,7-trimethyl-11-(pyridin-2ylmethyl)-
1 .4.7.10-tetraazacyclododecane, 1 ,4,8,11 -tetraazacyclododecane, 1 ,4,8,11- tetrakis(pyridin-2ylmethyl)-1 ,4,8,11 -tetraazacyclododecane, 1 -methyl-4,8, 11 - tri s (py ri d i n-2y I m ethy I)- 1 ,4,8,11 -tetraazacyclododecane, 1 ,4-dimethyl-8, 11 - bi s( py ri d i n- 2ylmethyl)-1 ,4,8,11 -tetraazacyclododecane, and 1 ,4,8-trimethyl-11-(pyridin-2ylmethyl)- 1 ,4,8,11 -tetraazacyclododecane and 1 ,4,8,11 -tetramethyl-1 ,4,8,11- tetraazacyclododecane.
In some embodiments, in particular when the complex is a manganese complex, ligands of formula (IV) may be tetraaza-1 , 4, 7, 10-cyclododecane-based and tetraaza-
1.4.8.11 -cyclotetradecane-based ligands of formula (IV) wherein each R group is hydrogen or Ci-2oalkyl. Within these ligands, R is typically hydrogen or methyl. According to yet more particular embodiments, ligands of formula (IV) include 1 ,4,7,10- tetraazacyclododecane, 1 ,4, 7, 10-tetramethyl-1 , 4, 7,10-tetraazacyclododecane,
1 .4.8.11 -tetraazacyclododecane and 1 ,4,8, 11 -tetramethyl-1 ,4,8, 11 - tetraazacyclododecane.
According to further embodiments, the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formulae (V), (V-B) or (V-C):
(V) (V-B) (V-C) wherein: each -R1 independently is selected from -CH2N(Ci-C24alkyl)2, -CH2NR7 or an optionally Ci-Cealkyl-substituted heteroaryl group selected from pyridin-2-yl, pyrazineyl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1-yl, 1 ,2,4-triazol-3-yl and thiazol-2-yl; each -R2 independently represents -R4-R5; each -R3 and each -R6 each independently represents hydrogen, or a group selected from Ci-Cealkyl, Ce-C aryl, Cs-C heteroaryl, Ce-C arylCi-Cealkyl and Cs-C heteroarylCi-Cealkyl, each of which groups may be optionally Ci-Cealkyl- substituted; each -R4- independently represents optionally Ci-Cealkyl-substituted C1- Cealkylene; each -R5 independently represents an -CH2N(Ci-C24alkyl)2 group, -CH2NR7 or an optionally Ci-Cealkyl-substituted heteroaryl group selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol- 2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, and thiazol-2-yl; each -NR7 independently represents a moiety in which R7 and the nitrogen atom N to which it is attached represents a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to R4 through the nitrogen atom N; and
Q2 represents a bridge selected from the group consisting of a Ci-ealkylene moiety Ce- arylene moiety or a moiety comprising one or two Ciwalkylene units and one Ce- arylene unit, which bridge is optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups.
In some embodiments, in particular when the complex is a manganese complex, no -R3 or -Re may be one of the possibilities permitted for -R1. It will be understood that ligands of formulae (V-B) and (V-C) are effectively dimers of ligands of formula (V) in which bridge Q2 takes the place of the R6 groups, or the R3 groups respectively. Of the ligands of formulae (V), (V-B) and (V-C), ligands of formula (V) are most typical. Amongst the bridge-containing ligands, ligands of formula (V-B) more typical than ligands of formula (V-C). Additionally, the following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of the ligands of formulae (V), (V-B) and (V-C):
• groups having the same descriptor, e.g. R1 , R2 (and, within the definition of R2, R4 and R5), R3, R6 and Q2 etc, are the same;
• R1 is optionally substituted pyridin-2-yl, in particular unsubstituted pyridin-2-yl;
• in embodiments in which -R1 is selected from -CH2N(Ci-24alkyl)2 and -CH2NR7, the nitrogen-containing group attached to the methylene group recited for these possibilities is selected from the group consisting of -NMe2, -NEt2, -N(i-Pr)2,
-R4- is -CH2-.
• where an alkyl-substituted heteroaryl group, R5 is optionally substituted pyridin- 2-yl, with the unsubstituted pyridin-2-yl being most typical;
• according to other particular embodiments, R5 may be -CH2N(Ci-C24alkyl)2 group or -CH2NR7, the nitrogen-containing group attached to the methylene group recited for these possibilities being selected from the group consisting of NMe2,
NEt2, N(i-Pr)2,
• each R3 and each R6 independently represents hydrogen, or a group selected from Ci-Cealkyl, Ce-C aryl, Ce-C arylCi-Cealkyl, Cs-Cwheteroaryl, Ce-C arylCi- Cealkyl and Cs-C heteroarylCi-Cealkyl, each of which groups may be optionally Ci-Cealkyl-substituted;
• particularly where the complex is a manganese complex, each R3 and each R6 independently represents hydrogen, or a group selected from Ci-Cealkyl, Ce- C aryl and Ce-C arylCi-Cealkyl, each of which groups may be optionally Ci- Cealkyl-substituted;
• each R3 is selected from hydrogen, methyl and benzyl;
• Q2 is selected from-CH2CH2-, -CH2CH2CH2- and -CH2CHOHCH2-, each of which is optionally Ci-Cealkyl-substituted, with the bridge typically being unsubstituted; • each R6 is typically selected from hydrogen, methyl, benzyl, and pyiridin- 2ylmethyl, with R6 most typically being selected from methyl and pyiridin- 2ylmethyl;
• particularly where the complex is a manganese complex, each R6 is typically selected from hydrogen, methyl, and benzyl, with R6 most typically being methyl. According to particular embodiments, the ligand of formula (V) is N-methyl-N-
(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine (MeN3Py) or N-benzyl-N-(pyridin-2-yl- methyl)-bis(pyridin-2-yl)methylamine (BzN3Py), both which are disclosed by Klopstra et al. (Eur. J. Inorg. Chem., 4, 846-856 (2006)). Further selected preferred ligands of formula (V) are N,N-b/s(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine (N4Py), which is disclosed in WO 95/34628; N, N-b/s(pyridin-2-yl-methyl)-1 , 1 -bis(pyridin-2-yl)-1 - aminoethane (MeN4py), as disclosed in EP 0 909 809, N,N-bis(pyridin-2-yl-methyl-1 , 1- bis(pyridin-2-yl)-2-phenyl-1 -aminoethane as disclosed in EP 0 909 809. Additional examples of ligands of formula (V) include: N-methyl-N-(pyridin-2-ylmethyl)-1 ,1- bis(pyridin-2-yl)-1 -aminoethane, N-benzyl-N-(pyridin-2-ylmethyl)-1 ,1-bis(pyridin-2-yl)-1- aminoethane, N-methyl-N-(pyridin-2-ylmethyl)-1 ,1-bis(pyridin-2-yl)-2-phenyl-1- aminoethane and N-benzyl-N-(pyridin-2-ylmethyl)-1 ,1-bis(pyridin-2-yl)-2-phenyl-1- aminoethane. Another example of ligand of formula (V) is N-methyl-N-(pyridin-2-yl- methyl)-bis(pyridin-2-yl)methylamine.
In some embodiments, the ligand of formula (V-B) is selected from N-methyl- N,N’,N’-tris(pyidin-2-ylmethyl)ethylenediamine, N-butyl-N,N’,N’-tris(pyridin-2-ylmethyl)- 1 ,2-ethylene-diamine, N-octyl-N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene-diamine, N, N, N’, N’-tetrakis(pyridin-2-yl-methyl)ethylene-1 ,2-diamine, N, N, N’, N’- tetrakis(benzimidazol-2-ylmethyl)ethylene-1 ,2-diamine, and 2,6-bis(pyridin-2-ylmethyl)- 1 ,1 ,7,7-tetrakis(pyridin-2-yl)-2,6- diazaheptane.
According to further embodiments, the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formula (VI):
N(CY2-R1)3 (VI) wherein: each -R1 is independently selected from -CY2N(Ci-C24alkyl)2; -CY2NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci .ealkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; or represents an optionally Ci-Cealkyl- substituted heteroaryl group selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-1-yl, pyrazol-3-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1 -yl, 1 ,2,4-triazol-3-yl and thiazol-2-yl; and each Y is independently selected from H, CH3, C2H5, C3H7.
The following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of the ligands of formula (VI):
• each Y is H;
• -R1 is selected from -CH2N(Ci-C24alkyl)2 and -CH2NR7, with particular embodiments being those in which the nitrogen-containing group attached to the methylene group recited for these possibilities is selected from the group consisting of -NMe2, -NEt2, -N(i-Pr)2,
• each R1 is often optionally substituted pyridin-2-yl;
• each R1 is more often unsubstituted pyridin-2-yl.
According to a specific embodiment, the ligand of formula (VI) is N,N,N- tr/s(pyridin-2-yl-methyl)amine (TPA), which has, for example, been described in US Patent Nos 5,850,086 (Que, Jr. et al.) and 6,153,576 (Blum et al.).
According to further embodiments, the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formulae (VII) or (VII- B):
R1 R2N-X-NR1 R2 (VII); and R1 R2N-X-NR2(-Q2-R2N)n-X-NR1 R2 (Vll-B); wherein:
-X- is selected from -CY2CY2-, cis- or trans-1 ,2-cyclohexylene, -CY2CY2CY2-, - CY2C(OH)YCY2-, with each Y being independently selected from H, CH3, C2H5 and C3H7; n is an integer from 0 to 10; each R1 group is independently an alkyl, heterocycloalkyl, heteroaryl, aryl, arylalkyl or heteroarylalkyl group, each of which may be optionally substituted with a substituent selected from the group consisting of hydroxy, alkoxy, phenoxy, phosphonate, carboxylate, carboxamide, carboxylic ester, sulfonate, amine, mono- or dialkylamine and N+(R3)s, wherein R3 is selected from hydrogen, alkyl, alkenyl, arylalkyl, arylalkenyl, hydroxyalkyl, aminoalkyl, and alkyl ether; each R2 is -CZ2-R4, with each Z being independently selected from H, CH3, C2H5, C3H7; and each -R4 being independently selected from optionally substituted - N(Ci-C24alkyl)2; -NR7, wherein each -NR7 independently represents a moiety in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-ealkyl groups, which is connected to CZ2 through the nitrogen atom N; and an optionally Ci-Cealkyl-substituted heteroaryl group selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3- yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1 -yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, and thiazol-2-yl; and CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and
Q2 is a bridge selected from the group consisting of a Ci-ealkylene bridge, a Ce- arylene bridge or a bridge comprising one or two Ci.salkylene units and one Ce- arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups.
In some embodiments, in particular when the complex is a manganese complex, n is 1. In some cases, no R1 may be one of the possibilities permitted for R2.
In some embodiments, again particularly when the complex is a manganese complex, each -R2 group is independently -CZ2-R4, with each Z being independently selected from H, CH3, C2H5, C3H7; and each -R4 being independently selected from optionally substituted -N(Ci-C24alkyl)2; -NR7, wherein each -NR7 independently represents a moiety in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-ealkyl groups, which is connected to CZ2 through the nitrogen atom N; and an optionally Ci-Cealkyl-substituted heteroaryl group selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin- 2-yl, pyrazol-1-yl, pyrazol-3-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2- yl, pyrimidin-2-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1-yl, 1 ,2,4-triazol-3-yl and thiazol-2-yl.
The following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of the ligands of formulae (VII) and (Vll-B):
• each Y is typically H;
• X is typically -CH2CH2- or 1 ,2-cyclohexylene;
• n is typically an integer from 0 to 4, more typically from 0 to 3, even more typically 0 to 2, and most typically n=0 or 1 , and, where the complex is a manganese complex, n is typically 1 ;
• Q2 is typically an ethylene, n-propylene bridge, or cis- or trans-1 ,2-cyclohexylene;
• particularly when the complex is a manganese complex, Q2 is typically an ethylene or n-propylene bridge;
• each Z is typically hydrogen;
• often, and particularly when the complex is an iron complex, X =Q2;
• R4, for example where -R4 is -NR7 or -N(Ci-C24alkyl)2, is selected from the group consisting of -NMe2, -NEt2, -N(i-Pr)2,
• where R4 is selected from the group consisting of optionally Ci-Cealkyl- substituted pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3- triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1 -yl or thiazol-2-yl group, this will be typically be selected from optionally Ci-Cealkyl- substituted pyridin-2-yl, imidazol-2-yl, imidazol-4-yl or benzimidazol-2-yl group, with unsubstituted pyridin-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl groups being more typical, and unsubstituted pyridin-2-yl most typical;
• often, and particularly when the complex is a manganese complex, two R4 groups (or four R4 groups in ligands of formula (Vll-B) are selected from pyridin-2-yl, imidazol-2-yl, imidazol-4-yl, or benzimidazol-2-yl (each of which may be optionally Ci-Cealkyl-substituted), particularly wherein Z is hydrogen, more typically optionally substituted pyridin-2-yl wherein Z is hydrogen, and most typically unsubstituted pyridin-2-yl wherein Z is hydrogen (i.e. two R2 groups (four in ligands of formula (Vll-B) are pyridin-2-ylmethyl); and/or two R1 groups are independently optionally substituted C1-C24 alkyl groups, more typically unsubstituted C1-C24 alkyl groups, for example C1-C18 alkyl groups, such as wherein two R1 groups are each methyl;
• either one or both R1 groups in Formulae (VII) or (Vll-B) can be independently optionally substituted C1-C24 alkyl groups, more typically unsubstituted C1-C24 alkyl groups, for example C1-C18 alkyl groups, such as wherein one or both R1 groups are methyl;
• either one or both R1 groups in Formula (VII) or (Vll-B) can be independently optionally substituted C6-C arylCi-C24alkyl groups, more typically unsubstituted C6-CioarylCi-C24alkyl groups, for example Ce-C arylCi-C^alkyl groups, most typically benzyl;
• either one or both R1 groups in Formulae (VII) or (Vll-B) can be independently CZ2R4, wherein Z is as defined for moiety R2 and typically hydrogen, R4 can be an optionally Ci-Cealkyl-substituted pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol- 2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4- triazol-3-yl, 1 ,2,4-triazol-1 -yl, and thiazol-2-yl, this will be typically be selected from optionally Ci-Cealkyl-substituted pyridin-2-yl, imidazol-2-yl, imidazol-4-yl, and benzimidazol-2-yl, more typically pyridin-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, or benzimidazol-2-ylmethyl;
• often all R1 groups in Formulae (VII) or (Vll-B) are the same and typically selected from pyridin-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, or benzimidazol-2-ylmethyl;
• more often, for formula (VII) one R1 group is the same as both R2 groups and typically all selected from pyridin-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4- ylmethyl, or benzimidazol-2-ylmethyl; equally often, both R1 groups are selected from pyridin-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, or benzimidazol-2-ylmethyl;
• particularly when the complex is a manganese complex, each R1 group is independently an alkyl, aryl or arylalkyl group, each of which may be optionally substituted with a substituent selected from the group consisting of hydroxy, alkoxy, phenoxy, phosphonate, carboxylate, carboxamide, carboxylic ester, sulfonate, amine, mono- or dialkylamine and N+(R3)s, wherein R3 is selected from hydrogen, alkyl, alkenyl, arylalkyl, arylalkenyl, hydroxyalkyl, aminoalkyl, and alkyl ether.
Specific embodiments of ligands of formula (VII) are N,N’-dimethyl-N,N’- bis(pyridin-2-ylmethyl)ethylene-1-2-diamine and N,N’-dimethyl-N,N’-bis(pyridin-2- ylmethyl)-cyclohexane-1-2-diamine, as disclosed by J Glerup et al. (Jnorg. Chern., 33, 4105-4111 (1994)). Specific embodiments of ligands of formula (VII) wherein one R1 and two R2 are -CH2-R4 are described in WO 02/077145 and EP 1 001 009 A (trispicen ligands). Examples of most suitable trispicen ligands are N-Ci-C2o-alkyl-N,N’,N’- tris(pyridin-2-ylmethyl)-1 ,2-ethylene-diamine, with N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)-1 ,2-ethylene-diamine, N-butyl-N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene- diamine, and N-octyl-N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene-diamine being most preferred. The ligand Tpen (N, N, N’, N’-tetrakis(pyridin-2-yl-methyl)ethylene-1 ,2- diamine) is described in WO 97/48787. The synthesis of the ligand N, N, N’, N’- tetrakis(benzimidazol-2-ylmethyl)ethylene-1 ,2-diamine has been described by S. Tong et al. (Open Journal of Inorganic Chemistry, 2, 75-80 (2012)). Other suitable trispicens are described in WO 02/077145 and EP 1 001 009 A. Further examples of trispicens are described in WO 00/12667, W02008/003652, WO 2005/049778, EP 2 228 429 and EP 1 008 645.
According to further embodiments, the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formulae (VIII) or (VIII- B):
(VIII) (Vlll-B) wherein: each Q group independently represents -CY2- or -CY2CY2-, in which each Y is independently selected from hydrogen, Ci-24alkyl, or a Ce- aryl; each D group independently represents a heteroarylene group or a group of the formula -NR-, with the proviso that at least one D group represents a heteroarylene group; each D1 group represents a group of the formula -NR’-; the two -R’ groups of the two D1 groups together form bridging moiety -Q2-; Q2 is a bridge selected from the group consisting of a Ci-ealkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce- C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; and each R group independently represents H, Ci-24alkyl, Ce- aryl or Cs-wheteroaryl.
The following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of the ligands of formulae (VIII) and (Vlll-B):
• each R is typically independently selected from hydrogen or methyl;
• where a bridge Q2 is present, this is typically an ethylene or n-propylene bridge;
• each R group is typically the same;
• each Q is typically -CY2-;
• Y is typically hydrogen and thus each Q is typically -CH2-; and
• where a group D is heteroarylene, this is typically pyridylene, in particular pyridin- 2,6-diyl.
According to particular embodiments, ligands of formula (VIII) are of formula (VIII- A), in which wherein R is as defined for formulae (VIII) and (Vlll-B), including the particular embodiments immediately hereinbefore described:
(Vlll-A).
According to specific embodiments, ligands of formula (VIII) (and formula (VIII- A)) are selected from 2,11-diaza[3.3](2,6-pyridinophane) (a compound of formula (VIII- A) in which each R is hydrogen) and N,N’-dimethyl-2,11-diaza[3.3](2,6-pyridinophane) (a compound of formula (Vlll-A) in which each R is methyl), as described in WO 99/065905 A1 (Unilever pic et al.). According to further embodiments, the chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms is of formula (IX): R1-CY2-(NR3)-CY2-R2-CY2-(NR3)-CY2-R1 (IX) wherein: each Y is independently selected from H, CH3, C2Hs and C3H7; each R1 is independently selected from an optionally Ci-Cealkyl-substituted Cs- Cwheteroaryl group, whereby the Cs-Cwheteroaryl group is selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1 - yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, and thiazol-2-yl;
R2 is selected from an optionally Ci-Cealkyl-substituted Cs-Ccheteroarylene group, whereby the Cs-Ccheteroarylene group is selected from pyridin-2,6-diyl, pyrazin- 2,6-diyl, pyrazol-3,5-diyl, pyrazol-1 ,3-diyl, pyrrol-2,5-diyl, imidazol-2,5-diyl, imidazol-1 ,4- diyl, pyrimidin-2,6-diyl, 1 ,2,4-triazol-3,5-diyl, 1 ,2,4-triazol-1 ,3-diyl, 1 ,2,4-triazol-2,4-diyl, 1 ,2,3-triazol-1 ,4-diyl, 1 ,2,3-triazol-2,5-diyl, and thiazol-2,5-diyl; each R3 is independently selected from optionally Ci-Ce-substituted Ci-24alkyl, Ce- aryl, C6-ioarylCi-C24alkyl, Cs-wheteroaryl, C5- heteroarylCi-C24alkyl.
The following features, alone or in combination, as the context permits (i.e. where not conflicting) are typical (but not essential) features of the ligands of formula (IX):
• each Y is typically hydrogen;
• each R1 is independently selected from an unsubstituted Cs-Cwheteroaryl group, the Cs-Cwheteroaryl group being typically independently selected from pyridin-2- yl, quinolin-2-yl, imidazol-2-yl , and thiazol-2-yl;
• each R1 is the same;
• each R1 = pyridin-2-yl is most typical;
• R2 is typically unsubstituted pyridin-2,6-diyl;
• each R3 is independently selected from Ci-Cc substituted Ci- alkyl, Cc-warylCi- C alkyl, pyridin-2-ylmethyl, pyrazin-2-ylmethyl, quinolin-2-ylmethyl, pyrazol-1 - ylmethyl, pyrazol-3-ylmethyl, pyrrol-2-ylmethyl, imidazol-2-ylmethyl, imidazol-4- ylmethyl, benzimidazol-2-ylmethyl, pyrimidin-2-ylmethyl, 1 , 2, 3-triazol-1 -ylmethyl, 1 ,2,3-triazol-2-ylmethyl, 1 ,2,3-triazol-4-ylmethyl, 1 ,2,4-triazol-3-ylmethyl, 1 ,2,4- triazol-1 -ylmethyl, and thiazol-2-ylmethyl;
• often, each R3 is independently selected from unsubstituted Ci-i2alkyl, CcarylCi- Ci2alkyl, pyridin-2-ylmethyl, quinolin-2-ylmethyl, pyrazol-1 -ylmethyl, pyrazol-3- ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, benzimidazol-2-ylmethyl, 1 ,2,3-triazol-1 -ylmethyl, 1 ,2,3-triazol-2-ylmethyl, 1 ,2,3-triazol-4-ylmethyl, 1 ,2,4- triazol-3-ylmethyl, 1 , 2, 4-triazol-1 -ylmethyl, and thiazol-2-ylmethyl;
• more typically, each R3 is independently selected from unsubstituted Ci-salkyl, CearylCH2, pyridin-2-ylmethyl, quinolin-2-ylmethyl, imidazol-2-ylmethyl, imidazol- 4-ylmethyl, benzimidazol-2-ylmethyl;
• even more typically each R3 is independently selected from methyl, CH2C6H5, and pyridin-2-ylmethyl;
• each R3 is the same.
In a specific embodiment of the ligands of formula (IX), Y=H, R1 = pyridin-2-yl, R2=pyridin-2,6-diyl, and R3 = methyl, i.e. , is 2,6-bis[(A/-methyl-{A/-(2- pyridylmethyl)}amino)methyl]pyridine.
Another class of ligands that may be present as polydentate ligands of the manganese complexes are porphyrin or porphyrazine ligands. These are described in detail in WO 2012/027216 A1 (The Trustees of Princeton University).
We use term porphyrin herein in accordance with its customary meaning in the art to mean a tetradentate tetracyclic macrocycle, comprising four pyrrole rings linked by four methine bridges, each of the pyrrole rings being connected at its 2- and 5-carbon atoms to an adjacent pyrrole moiety through a methine (=C(H)-) biradical. The parent compound is named porphyrine; when substituted, the resultant compounds are known as porphyrins.
Likewise, we use term porphyrazine herein in accordance with its customary meaning in the art to refer to a class of macrocycle related to porphyrins, but in which the four pyrrole rings are linked linked by -N=, rather than methine, bridges, with the parent compound being known as porphyrazine and its derivatives as porphyrazines. For the avoidance of doubt, will be understood that porphyrazine derivatives comprising cyclic moieties fused to the 3- and 4-carbon atoms of the pyrrole moieties within porphyrazine are porphyrazines.
In some embodiments, particularly when the complex is an iron complex, the complex does not comprise a porphyrin or porphyrazine ligand.
According to particular embodiments, particularly when the complex is an iron complex, the polydentate ligand is not a tetrapyrrole-containing compound. By "tetrapyrrole-containing compound" is meant herein a compound comprising four pyrrole rings or reduced forms thereof (such as the pyrroline ring found in the chlorin ring of chlorophylls; a chlorin ring being made up of three pyrrole and one pyrroline (3,4- dihydropyrrole) moieties linked by four methine (-C(H)=) bridges, each of the pyrrole and pyrroline moieties being connected at its 2- and 5-carbon atoms to an adjacent pyrrole or pyrroline moiety through a methine biradical).
In addition to porphyrins, porphyrazines and chlorins, there are a variety of other macrocyclic compounds based either on four pyrrole or reduced pyrrole units linked either through methine or imine (-N=) bridges. For example, corrin rings comprise four pyrroline moieties linked by three methine bridges, all but one of the pyrroline moieties being connected at their 2- and 5-carbon atoms to an adjacent pyrroline moiety through a methine biradical; two of the pyrroline moieties, however, are directly connected, from the 2-carbon of one to the 5-carbon atom of the other. Phthalocyanines are macrocycles comprising four pyrrole-based five-membered rings linked by four imine bridges, each of the five-membered rings having a benzene ring fused to the 3- and 4-positions of the five-membered ring, and each of the five-membered rings being connected at its 2- and 5-carbon atoms to an adjacent five-membered ring through an imine biradical.
According to those embodiments of the invention in which the polydentate ligand is not a tetrapyrrole-containing compound, each of these immediately aforementioned classes of macrocycle is excluded, it being understood that use of the term tetrapyrrole- containing compounds to embrace compounds not necessarily comprising four pyrrole rings is consistent with the use prevalent in the art to describe, as tetrapyrrole-containing compounds, compounds such as phthalocyanines and chlorins, even although these compounds, strictly speaking structurally, do not comprise four pyrrole rings.
Where the complex comprises porphyrin or porphyrazine ligands, the complex also comprises manganese ions, i.e. the complex is a manganese complex. Typically, when chelated to a manganese ion, two of the pyrrole moieties within a porphyrin or porphyrazine ligand are deprotonated, and consequently negatively charged. Subsequently, the overall charge of the resultant manganese complex is reduced by 2. Thus, double deprotonated porphyrin or porphyrazine ligands often stabilise manganese ions with a more positive oxidation state. In some embodiments, when the ligand is a porphyrin or porphyrazine ligand, the one or more manganese ions have oxidation state(s) of one or more selected from the group consisting of II, III and IV. In some embodiments, when the ligand is a porphyrin or porphyrazine ligand, the manganese complex further comprises up to two additional ligands independently selected from halide, oxo, aquo, hydroxo, cyanide, hydrogenphosphate, Ci-Csalcohol and Ci- Csalkoxide.
In some embodiments, the porphyrin is of formula (X): wherein: each R1, R2, R3, and R4 is a 5- to 10-membered N-heteroaryl optionally substituted with one or more selected from the group consisting of Ci-24alkyl, C3- scycloalkyl, C^cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci- 24alkylphenyl, Ci.24alkylnaphthyl, Ci.24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R1a, R2a, R3a and R4a is independently selected from the group consisting of Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci-24alkylphenyl, Ci.24alkylnaphthyl, Ci-24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; and n is 0 to 2.
For the avoidance of doubt, where two of the pyrrole moieties within the porphyrin ligand of formula (X) are deprotonated, the ligand is of formula (X-a):
In some embodiments, n of formula (X) or (X-a) is 0.
Often, R1, R2, R3, and R4 of formula (X) or (X-a) are independently selected from formulae (X-b1), (X-b2), (X-b3) and (X-b4):
wherein the wavy line bisects the C-R1 , C-R2, C-R3 and C-R4 bond; and Rs, Re, R7, Rs, Rg and R10 are independently selected from the group consisting of hydrogen, Ci-24alkyl, Cs-scycloalkyl, C^scycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci-24alkynyl, Ci^alkylCe-ioaryl, Ci.24alkoxy and phenoxy, each of which is optionally substituted with Ci-ealkyl, halo, CH2CF3 and CF3.
Typically, the R1, R2, R3 and R4 groups are the same. Often, the R5, Re, R7, Rs, Rg and R10 groups are methyl groups.
Preferred ligands of compound (X) are Tetra-(N-methyl)-2-pyridyl-porphyrin (TM2PyP), Tetra-(N-methyl)-4-pyridyl-porphyrin (TM4PyP), Tetra(N,N-dimethyl)- imidazolium-porphyrin (TDMImP), Tetra(N,N-dimethyl)-benzimidazolium-porphyrin (TDMBImP), and 5,10,15,20-tetra(4-pyridyl)-21 H,23H-porphine tetrakis(methochloride). In some embodiments, the porphyrazine ligand is of formula (XI): wherein: A1, A2, A3, A4, B1, B2, B3, B4, C1, C2, C3, C4, D1, D2, D3 and D4 are independently selected from N, C-H, C-Rn, N+-H and N+-Rn with the proviso that no more than one of Ai, Bi, Ci , and Di is N, N+-H or N+-Rn, no more than one of A2, B2, C2, and D2 is N, N+-H or N+-Rn, no more than one of A3, B3, C3, and D3 is N, N+-H or N+-Rn, and no more than one of A4, B4, C4, and D4 is N, N+-H or N+-Rn, and wherein: each Rn is independently selected from Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci-24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci.24alkylphenyl, Ci.24alkylnaphthyl, Ci- 24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R1a, R2a, R3a and R4a is independently selected from the group consisting of Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci-24alkylphenyl, Ci.24alkylnaphthyl, Ci-24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R1, R2, R3, and R4 is a 5- to 10-membered N-heteroaryl optionally substituted with one or more selected from the group consisting of Ci-24alkyl, C3- scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci- 24alkylphenyl, Ci.24alkylnaphthyl, Ci.24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; and n is 0 to 2.
For the avoidance of doubt, where two of the pyrrole moieties within the porphyrin ligand of formula (XI) are deprotonated, the ligand is of formula (Xl-a):
In some embodiments, n of formula (XI) or (Xl-a) is 0. In some embodiments, each Rn of formula (XI) or (Xl-a) is Ci-24alkyl, C3- scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, Ce- aryl, Ci.24alkynyl, Ci^alkylCe- aryl, Ci- 24alkoxy and phenoxy, each of which is optionally substituted with Ci-ealkyl, halo, CH2CF3 and CF3.
Typically, Di , D2, D3, and D4 are the same, often each being N+-Rn. Typically, A1, B1, C1, A2, B2, C2, A3, B3, C3, A4, B4, and C4 are the same, often each being CH. Preferably, each Rn is methyl.
A preferred ligand of formula (XI) is TM23PyPz, which is of formula (Xl-a):
(Xl-a)
It will be understood that, in the polydentate ligands of formulae (l-B), (ll-B), (V- B), (V-C), (Vll-B) and (Vlll-B), each of which comprises a bridge, the resultant polydentate ligands are capable of chelating two iron or manganese ions. Such polydentate ligands, as well as the other polydentate ligands described herein may be readily accessed by the skilled person.
For example, with regard to ligands of formulae (l-B), the skilled person will recognise, for example, if Q=1 ,3-propylene (-CH2CH2CH2-), that by reacting the appropriate piperidone precursor, formaldehyde and 1 ,3-diamino-propane, the desired bridged bispidon ligand can be obtained, as described by K. Born et al. (J. Biol. Inorg. Chem., 12, 36-48 (2007)).
With regard to ligands of formulae (ll-B), reference is made to the procedure described by K-0 Schaefer et al. (J. Am. Chem. Soc., 120, 131040-13120 (1998)), describing the synthesis of bridged triazacyclononane (TACN) compounds.
With regard to ligands of formulae (V-B), the skilled person will recognise, for example, that N-(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine (N3py) (the synthesis of which is described by G. Roelfes etal. (J. Am. Chem. Soc., 122, 11517-11518 (2000)), may be reacted with, 1 ,2-dibromoethane, for example to yield 1 ,2-bis(N-(pyridin-2-yl- methyl)-bis(pyridin-2-yl)methylamine)-ethane, analogously to the synthesis of the TACN- bridged ligands described by K-0 Schaefer et al. (supra) or the procedure described by M Klopstra et al. (Eur. J. Inorg. Chem., 846-856 (2000)) involving reaction N3py with benzylchloride to produce benzyl-N3py.
With regard to ligands of formulae (V-C), the skilled person will recognise, for example, that N-methyl-N-(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine (MeN3py) (the synthesis of which is described by M Klopstra et al. (supra) may be reacted with BuLi at low temperature and then with, for example, dibromoethane to yield the bridged ligand, analogously to the synthesis of MeN4py and benzylN4py described elsewhere (see for example EP0909809B).
With regard to ligands of formula (Vll-B), the skilled person will recognise, for example that N,N’-bis(2-pyridylmethyl)ethylene diamine (prepared as described by L Xu et al (Inorg. Chem., 39, 5958-5963 (2000)) can be reacted with, for example, 1 ,3- dibromopropane (analogously to the synthesis of the TACN-bridged ligands described by K-0 Schaefer et al. (supra)), to yield 1 ,3-bis(N,N’-bis(2-pyridylmethyl)ethylene diamine)-propane. Subsequently, methylation can be effected to access the methylated ligand, 1 ,3-bis(N,N’-dimethyl-N,N’-bis(2-pyridylmethyl)ethylenediamine)-propane, analogously to synthesis of MeN3py by M Klopstra et al. (supra).
In case a polyamine based ligand of formula (Vll-B) is sought (i.e. wherein n > 1) with each R1 group = pyridin-2ylmethyl according to formula (Vll-B), the skilled person will understand that in such a case, the appropriate polyamine precursor, such as 1 ,4,7,10-tetraazadecane, can be allowed to react with picolylchloride, such as described in many articles (see e.g. L Xu et al (Inorg. Chem., 39, 5958-5963 (2000)), to yield N,N,N’,N”,N”’,N”’-pentakis(pyridine-2-ylmethyl)-1 ,4,7,10-tetraazadecane. Numerous permutations with other R1 groups or number of aliphatic amine groups according to formula (VII) are accessible by the skilled person.
With regard to ligands of formulae (Vlll-B), the skilled person will recognise, for example that 2,11-diaza[3.3](2,6-pyridinophane (see WO 99/065905 A1) can be reacted with 1 ,2-dibromoethane (analogously to the synthesis of the TACN-bridged ligands described by K-0 Schaefer et al. (supra)), to yield 1 ,2-bis(2,11-diaza[3.3](2,6- pyridinophane)ethane. Subsequently, methylation can be effected to access the methylated ligand, 1 ,2-bis(11-methyl-2,11-diaza[3.3](2,6-pyridinophane)ethane, analogously to synthesis of MeN3py by M Klopstra et al. (supra).
Ligands of formula (IX) can be either prepared by procedures as outlined above for different bridged ligands via a reaction of the appropriate amine-based precursor with e.g. dibromo-ethane, but they may also be prepared by reacting the appropriate free polyamine precursor with e.g. picolinic chloride, via the well-established procedures to couple picolinic chloride to free amines (see various references of the examples given in the patent application).
It will be understood that the procedures outlined above can be adapted to access other polydentate ligands of formulae (l-B), (ll-B), (V-B), (V-C), (Vl-B), (Vll-B), (Vlll-B) and (IX) within the normal ability of those of skill in the art and that alternative synthetic procedures will be readily evident to the skilled person.
Notwithstanding the discussion of polydentate ligands of formulae (l-B), (ll-B), (V- B), (V-C), (Vl-B), (Vll-B), (Vlll-B), and (IX) however, the polydentate ligands of the invention are often capable of chelating one iron or manganese ion and thus, of the chelants described above, chelants selected from the group consisting of ligands of formula (I), (II), (III), including (lll-A), (IV), (V), (VI), (VII), (VIII), including (Vlll-A), and (IX) are typical.
In some embodiments, the chelant is selected from formula (I), (II), (ll-B), (III),
(IV), (V), (V-B), (VI) and (VII). Typically, the chelant is selected from formula (I), (II), (IV),
(V), (V-B), (VI) and (VII).
In some embodiments, the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, dimethyl 2,4-di-(2-pyridyl)-3-(pyridin-2- ylmethyl)-7-methyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, dimethyl 9,9- dihydroxy-3-methyl-2,4-di-(2-pyridyl)-7-(1-(N,N-dimethylamine)-eth-2-yl)-3,7-diaza- bicyclo[3.3.1]nonane-1 ,5-dicarboxylate, dimethyl 2,4-di-(2-pyridyl)-3,7-dimethyl-3,7- diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N, N-bis(pyridin-2-yl-methyl-1 , 1 - bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N-(pyridin-2-yl-methyl)-bis(pyridin-2- yl)methylamine, N-benzyl-N-(pyridin-2-yl-methyl)-bis(pyridin-2-yl)methylamine, N- methyl-N,N’,N’-tris(pyridin-2-ylmethyl)ethylenediamine, N-butyl-N,N’,N’-tris(pyridin-2- ylmethyl)-1 ,2-ethylene-diamine, N-octyl-N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene- diamine, N, N, N’, N’-tetrakis(pyridin-2-yl-methyl)ethylene-1 ,2-diamine, N, N, N’, N’- tetrakis(benzimidazol-2-ylmethyl)ethylene-1 ,2-diamine, tris(pyridin-2-ylmethyl)amine, 1 ,4,7,10-tetrakis(2-pyridin-2-ylmethyl)-1 ,4,7,10-tetraazacyclododecane, 1-methyl-4,7- bis(py rid i n-2-y I methyl)- 1 ,4,7-triazacyclononane, 1 -methyl-4,7-bis(quinolin-2-ylmethyl)- 1 ,4,7-triazacyclononane, 1-ethyl-4,7-bis(quinolin-2-ylmethyl)-1 ,4,7-triazacyclononane, 2,6-bis(pyridin-2-ylmethyl)-1 ,1 ,7,7-tetrakis(pyridin-2-yl)-2,6- diazaheptane, 2,6- bis(pyridin-2-ylmethyl)-1 ,1 ,7,7-tetrakis(pyridine-2-yl)-2,6-diazaheptane (N,N’- bis(dipyridin-2-ylmethyl)-N,N’-bis(pyridin-2-ylmethyl)-1 ,3-diamino-propane), 1 ,4,7- trimethyl-1 ,4,7-triazacyclononane, 4, 11 -dimethyl-1 ,4,8, 11 - tetraazabicyclo[6.6.2]hexadecane and 5,10,15,20-tetra(4-pyridyl)-21 H,23H-porphine tetrakis(methochloride).
In particular embodiments, the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N, N-bis(pyridin-2-yl-methyl-1 , 1 - bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine, tris(pyridin-2-ylmethyl)amine, 1 ,4,7, 10-tetrakis(2-pyridin-2- ylmethyl)-1 ,4,7,10-tetraazacyclododecane, 1-ethyl-4,7-bis(quinolin-2-ylmethyl)-1 ,4,7- triazacyclononane and 2,6-bis(pyridin-2-ylmethyl)-1 , 1 ,7,7-tetrakis(pyridine-2-yl)-2,6- diazaheptane.
In yet more particular embodiments, the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N, N-bis(pyridin-2-yl-methyl-1 , 1 - bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine, tris(pyridin-2-ylmethyl)amine, and 2,6-bis(pyridin-2-ylmethyl)- 1 ,1 ,7,7-tetrakis(pyridine-2-yl)-2,6-diazaheptane.
In particular embodiments, the chelant is dimethyl 2,4-di-(2-pyridyl)-3-methyl-7- (pyridin-2-ylmethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate.
As described herein, the iron or manganese complexes referred to in connection with the various aspects of this invention are formed from a chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms, including the specific examples of such ligands described in detail herein. These ligands comprise donor atoms, which coordinate to one or more iron or manganese ions of the iron or manganese complexes described herein.
The concentration of the iron or manganese complexes in the aqueous media described herein is typically about 0.001 to about 50 pM, often about 0.01 to about 20 pM, and according to particular embodiments about 0.03 to about 5 pM.
It is to be understood that, whilst the complexes may be introduced into the methods of the first and third aspect of the invention, and the aqueous medium in accordance with the second aspect of the invention may be prepared from such complexes, per se, which we refer to herein as well-defined complexes, well-defined complexes are not an essential feature of the invention.
By a well-defined complex is meant herein (as the term is used customarily in the art) a pre-formed complex (i.e. not one prepared in situ), which has been, or may be, isolated such that it is susceptible to characterisation (i.e. definition) and analysis (e.g. to determine its structure and degree of purity). In contrast, a complex that is not well- defined is one that is prepared in situ without isolation from the medium (e.g. reaction medium) in which it is prepared, and optionally used. Well-defined complexes are not a mandatory feature of the present invention, however: an appropriate iron or manganese complex may be prepared by mixing an appropriate amount of polydentate ligand with an appropriate amount and source of iron or manganese ions, in a desired stoichiometry.
It will be understood that there is no particular limitation as to the source of the iron or manganese ions from which the iron or manganese complexes described herein may be prepared.
Typically, iron salts are selected from the group consisting of optionally hydrated FeCh, FeBr2, Fe(NOs)2, FeSC , Fe(CFsSO3)2, Fe(acetylacetonate)2, Fe(acetylacetonate)3, Fe(RsCOO)3 (including Fe(acetate)3) and Fe(RsCOO)2, wherein Rs is selected from a Ci-C24alkyl. Where the salt comprises two or more Rs groups, these can be the same or different. The alkyl moieties, by which is meant saturated hydrocarbyl radicals, may be straight-chain or comprise branched and/or cyclic portions. Often the iron salt is selected from the group consisting of optionally hydrated FeCh, FeBr2, Fe(NOs)2, FeSO4 and Fe(OAc)2.
Typically, manganese salts are selected from the group consisting of optionally hydrated MnCh, MnBr2, Mn(NO3)2, MnSO4, Mn(acetylacetonate)2, Mn(acetylacetonate)3, Mn(RsCOO)3 (including Mn (acetate^) and Mn(RsCOO)2, wherein Rs is selected from a C1-C24 alkyl. Where the salt comprises two or more Rs groups, these can be the same or different. The alkyl moieties, by which is meant saturated hydrocarbyl radicals, may be straight-chain or comprise branched and/or cyclic portions. Often the manganese salt is selected from the group consisting of optionally hydrated MnCl2, MnBr2, Mn(NO3)2, MnSO4 and Mn(OAc)2.
The term optionally hydrated is well known in the art. Metal salts often contain water molecules within a crystal lattice, which will remain present unless the hydrated metals salts are subjected to specific drying steps by heating or drying under reduced pressure. However, partially or fully dehydrated metal salts can also be used. For example, iron(ll)chloride, manganese (II) acetate and manganese (II) chloride can be bought as a tetrahydrate salt or as a dehydrated (anhydrous) salt. Commercial iron sulfate is commercially available in dehydrated (anhydrous), monohydrate, and heptahydrate forms. Commercial manganese sulfate is available in both tetrahydrate and monohydrate forms. The term “about” herein, when qualifying a number or value, is used to refer to values that lie within ± 5% of the value specified. For example, if a pH is specified to be about 1 to about 3.5, pH values of 0.095 to 3.675 are included.
According to particular embodiments of the invention, the complex used in accordance with the first and third aspect of the invention, or present in the composition of the second and fourth aspect, or kit of the seventh aspect of the invention, is preformed (used interchangeably herein with the term “well-defined”). Often it is desirable to use preformed iron or manganese complexes.
The iron or manganese complexes of use according to the various aspects of the invention are typically of the general formula (A1):
[MaLkXn]Ym (A1) in which:
M represents an iron ion selected from Fe(ll), Fe(lll), Fe(IV) and Fe(V) or a manganese ion selected from Mn(ll), Mn(lll), Mn(IV) and Mn(V);
L represents the one or more polydentate ligands defined herein, or a protonated or deprotonated derivative thereof; each X independently represents a coordinating species selected from any mono-, bi- or tri-charged anion or a neutral molecule able to coordinate an iron or manganese ion in a mono-, bi- or tridentate manner, preferably selected from O2', RBC>22' , RCOO; RCONR-, OH’, NO3 , NO, S2’, RS; PO4 3’, PO3OR2-, H2O, CO32; HCO3 , ROH, N(R)3, ROO; O2 2’, O2; RON, Ch, Br, OCN; SON; CN; N3; F; h, RO; CIO4; and CF3SOT , and more preferably selected from O2, RBO22; RCOO; OH; NOT, S2; RS; PO4 3; HPO4 2; H2O, CO32; HCO3; ROH, N(R)3, Cl; Br, OCN; SON; RCN, N3; F; I; RO; CIO4 , and CF3SOT ; each R independently represents a group selected from hydrogen, hydroxyl, -R” and -OR”, wherein R” = Ci-C2oalkyl, C2-C2oalkenyl, Ci-C2oheterocycloalkyl, Ce-C aryl, C5-Ci0heteroaryl, (C=O)H, (C=O)-Ci-C20alkyl, (C=O)-C6-Ci0aryl, (C=O)OH, (C=O)O-Ci- C20alkyl, (C=O)O-C6-Ci0aryl, (C=O)NH2, (C=O)NH(Ci-C20alkyl), (C=O)NH(C6-Ci0aryl), (C=0)N(Ci-C2oalkyl)2, (C=0)N(C6-Cioaryl)2, R” being optionally substituted by one or more functional groups E, wherein E independently represents a functional group selected from -F, -Cl, -Br, -I, -OH, -OR', -NH2, -NHR', -N(R')2, -N(R')3 +, -C(O)R', -OC(O)R', -COOH, -COO’ (Na+, K+), -COOR', -C(O)NH2, -C(O)NHR', -C(O)N(R')2, heteroaryl, -R', - SR', -SH, -P(R')2, -P(O)(R')2, -P(O)(OH)2I - P(O)(OR')2, -NO2, -SO3H, -SO3-(Na+, K+), - S(O)2R', -NHC(O)R', and -N(R')C(O)R', wherein R' represents Ce-C aryl, C7- C2oarylalkyl, or Ci-C2oalkyl each of which may be optionally substituted by -F, -Cl, -Br, - I, -NH3 +, -SO3H, -SO3’(Na+, K+), -COOH, -COQ-(Na+, K+), -P(O)(OH)2, or -P(O)(Q-(Na+, K+))2, and preferably each R independently represents hydrogen, Ci-C4oalkyl or optionally Ci-C2oalkyl-substituted Ce-C aryl, more preferably hydrogen or optionally substituted phenyl or naphthyl, or Ci-4alkyl;
Y is a non-coordinating counterion; a is an integer from 1 to 10, typically from 1 to 4, more typically still 1 or 2; k is an integer from 1 to 10 typically from 1 to 4, more typically still 1 or 2; n is an integer from 1 to 10, typically from 1 to 4; and m is zero or an integer from 1 to 20, and is typically an integer from 1 to 8.
Generally, the iron ion(s) of the complex are selected from the group consisting of Fe(ll), Fe(lll) and Fe(IV) and the manganese ion(s) of the complex are selected from the group consisting of Mn(ll), Mn(lll) and Mn(IV). Often, the complex comprises one or two such iron or manganese ions. Where the complex comprises two or more iron or manganese ions they may be of the same oxidation state or different oxidation states. Also where the complex comprises two metal ions, one metal ion may be iron and the second metal ion may be manganese.
As used herein, within the definitions provided above for formula (A1) and elsewhere, unless a context expressly dictates to the contrary, the following definitions apply:
• By alkyl is meant herein a saturated hydrocarbyl radical, which may be straightchain, cyclic or branched. By alkylene is meant an alkyl group from which a hydrogen atom has been formally abstracted. Typically alkyl and alkylene groups will comprise from 1 to 25 carbon atoms, more usually 1 to 10 carbon atoms, more usually still 1 to 6 carbon atoms. The simplest alkylene group is methylene (-CH2-).
• By alkenyl is meant an unsaturated hydrocarbyl radical, which may be straightchain, cyclic or branched, comprising one or more, typically one, non-aromatic carbon-carbon double bonds. By alkenylene is meant an alkenyl group from which a hydrogen atom has been formally abstracted. Typically alkenyl and alkenylene groups will comprise from 2 to 25 carbon atoms, more usually 2 to 10 carbon atoms, more usually still 2 to 6 carbon atoms. The simplest alkenylene group is ethenylene (-CH=CH-).
• By alkynyl is meant an unsaturated hydrocarbyl radical, which may be straightchain, cyclic or branched, comprising one or more, typically one, carbon-carbon triple bonds. By alkynylene is meant an alkynyl group from which a hydrogen atom has been formally abstracted. Typically alkynyl and alkynylene groups will comprise from 2 to 25 carbon atoms, more usually 2 to 10 carbon atoms, more usually still 2 to 6 carbon atoms.
• The term aromatic used herein embraces within its scope heteroaromatic. As known to those skilled in the art, and used herein, heteroaromatic moieties may be regarded a subset of aromatic moieties that comprise one or more heteroatoms, typically oxygen, nitrogen or sulfur, often nitrogen, in place of one or more ring carbon atoms and any hydrogen atoms attached thereto. Examples of heteroaromatic moieties, for example, include pyridine, furan, pyrrole and pyrimidine.
• Aromatic moieties may be polycyclic, i.e. comprising two or more fused aromatic (including heteroaromatic) rings. Naphthalene and anthracene are examples of polycyclic aromatic moieties, and benzimidazole is an example of a polycyclic heteroaromatic moiety.
• Aryl radicals and arylene diradicals are formed formally by abstraction of one and two hydrogen atoms respectively from an aromatic moiety. Thus phenyl and phenylene are the aryl radical and arylene diradical corresponding to benzene. Similarly, pyridyl and pyridylene (synonymous with pyridindiyl) are the heteroaryl radical and heteroarylene diradical corresponding to pyridine. Unless a context dictates to the contrary, pyridyl and pyridylene are typically 2-pyridyl and pyridine- 2,6-diyl respectively.
• By heterocycloalkane is meant a cycloalkane, typically a Cs-ecycloalkane, in which one or more CH2 moieties are replaced with heteroatoms, typically selected from the group consisting of nitrogen, oxygen and sulfur. Where the heteroatom is nitrogen, it will be understood that the CH2 moiety is formally replaced with NH, not N. By heterocycloalkyl is meant herein a radical formed formally by abstraction of a hydrogen atom from a heterocycloalkane. Typical examples of heterocycloalkyl groups are those in which the heterocycloalkyl is formed formally by abstraction of a hydrogen atom from the nitrogen atom. Typical heterocycloalkyl groups include pyrrolidin-1 -yl, piperidin-1-yl and morpholin-4-yl, i.e. in which the heterocycloalkyl is formed formally by abstraction of a hydrogen atom from the nitrogen atom of the parent heterocycloalkane. • By arylalkyl is meant aryl-substituted alkyl. Analogously, by aminoalkyl is meant amino-substituted alkyl, by hydroxyalkyl is meant hydroxy-substituted alkyl and so on.
• Various alkylene bridges are described herein. Such alkylene bridges are typically although not necessarily straight chain alkylene bridges. They may, however, be cyclic alkylene groups (e.g. a Cealkylene bridge may be cyclohexylene, and if so is typically cyclohexyl-1 , 4-ene). Where a bridge is, for example, a Ce-C arylene bridge, this may be, for example, phenylene or the corresponding arylene formed by abstraction of two hydrogen atoms from naphthalene. Where a bridge comprises one or two Ci-Csalkylene units and one Ce-C arylene unit, such bridges may be, for example, -CH2C6H4CH2- or - CH2C6H4-. Where present, phenylene is typically phenyl-1 , 4-ene. It will be understood that each of these bridges may be optionally substituted one or more times, for example once, with independently selected C1-C24 alkyl (e.g. C1-C18 alkyl) groups.
• By carboxamide is meant a compound or radical comprising the functional group -N(H)C(O)-.
• By carboxylic ester is meant a compound or radical comprising the functional group -OC(O)-.
• By alkyl ether is meant a radical of the formula -alkylene-O-alkyl, wherein alkylene and alkyl are as herein defined.
The counter ions Y in formula (A1) balance the charge z on the complex formed by the ligand(s) L, iron or manganese ion(s) and coordinating species X. If the charge z is positive, as it is in most cases, the iron or manganese complex comprises one or more iron or manganese ions and one or more non-coordinating counteranions Y. Examples of counteranions Y include RCOO; BPI , CIOT, BF4; PFe’, RSOT, RSOT, SO42; S20e2' , NOT, F; Cl; Br, or I; with R being hydrogen, Ci-C4oalkyl or optionally Ci-C2oalkyl- substituted Ce-C aryl.
The identity of the counteranion(s) Y is, however, not an essential feature of the invention. Suitable counterions Y include those which give rise to the formation of storage-stable solids. Where z is positive, counterions, including those for the preferred metal complexes, are often selected from Cl; Br; I; NOT, CIOT, PFe; RSOT, SO42; RSOT, CF3SO3; and RCOO; with R in this context being selected from H, C1-12 alkyl, and optionally Ci-ealkyl-substituted CeHs (i.e. wherein CeHs is substituted one or more times (e.g. once) with a Ci-ealkyl group; often CeHs is unsubstituted). Often, these will be selected from Cl; NOT, PFe’, tosylate, SO42; CF3SO3; acetate, and benzoate. Particularly often, these will be selected from the group consisting of Cl; NO3; SC>42' and acetate.
Where z is negative, suitable counterions include alkali metal ions, alkaline earth metal ions, (alkyl)ammonium cations (such as tetraCi.4alkylammonium cations), tetraarylphosphonium cations, and bis(triphenylphosphorananylidene)-ammonium cations for balancing the charge of the compound on a stoichiometric basis. The tetraarylphosphonium cations include, for example, tetraphenylphosphonium ions, or related ions with four aryl or four alkyl groups on phosphorus including any combination of aryl or alkyl, including mixed aryl and alkyl groups on the same phosphorus atom. The tetraalkylammonium ions may include, for example, tetraethyl ammonium, tetrapropyl ammonium and tetrabutyl ammonium ions, and tetralkyl ammonium ions with longer (e.g. C5-24) straight chain alkyl groups including ammonium ions with a combination of straight chain alkyl groups, or with four branched alkyl groups, or with mixtures of branched and straight chain alkyl groups. If z is negative, preferred counterions are those of alkali metal ions or alkaline earth metal ions, with Na+, K+, and Li+ being particularly preferred.
Those complexes that comprise chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms are typically mononuclear iron or manganese complexes comprising other monodentate ligands (X according to formula (A1)). Examples of suitable monodentate ligands include chloride, bromide or triflate (CFSSOT) anions. If for example iron(ll) or manganese(ll) species are used with chelants capable of chelating at least one iron or manganese ion through four neutral nitrogen atoms, two monanionic, monodentate ligands will neutralise the charge of the iron or manganese ion and no additional non-coordinating counterions will be present. However, if iron(lll), manganese(lll), iron(IV) or manganese(IV) species are formed, then additional counterions X will be present, such as those defined in formula (A1), chloride, triflate or hexafluorophosphate being most preferred. Other possibilities may be envisaged, such as a neutral tridentate nitrogen donor bound to an iron(lll) or manganese(lll) species, with three anionic monodentate ligands, such as chloride, bromide or triflate, rendering the charge of the complex zero.
In addition to anionic counterions, neutral monodentate ligands, such as acetonitrile or water, may be bound to the iron or manganese ion(s). It will be understood that this possibility may also give rise to a charged iron or manganese complex (i.e. with a bound Fe(ll) or Mn(ll) ion), and thus occasions the presence of non-coordinating counterions. This discussion is premised on an iron or manganese ion binding to 6 donor atoms. Although this is generally the case, it is not always so: Fe(ll), Mn(ll), Fe(lll) or Mn(lll) ions are, for example, known to give rise to, besides 6-coordinate complexes, 4, 5 or 7-coordinate complexes.
Complexes of formula (A1) typically comprise one or two iron or manganese ions.
For dinuclear iron or manganese complexes (i.e. iron or manganese complexes comprising two iron or manganese ions), there are often bridging ionic ligands presents, i.e. in addition to the bichelating polydentate ligands described herein. Examples of such additional bridging ligands include oxide (O2-), hydroxide (OH-) or Ci-ecarboxylate (i.e. RCC>2' wherein R is a Ci -salkyl group) ions, which bridge the two iron or manganese ions. Where present, an alkylcarboxylate ion is typically acetate. Typically, dinuclear complexes comprise two bridging ions, for example, two acetate ions.
In particular embodiments, the iron or manganese complex of use according to the various aspects of the invention is selected from the group consisting of [Fe(dimethyl
2.4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-one-
1.5-dicarboxylate)CI]CI, [Fe(N, N-bis(pyridin-2-yl-methyl-1 , 1 -bis(pyridin-2-yl)-1 - aminoethane)CI]CI, [Fe(N-methyl-N,N’,N’-tris(pyridin-2-ylmethyl)ethylenediamine)CI]CI, [Fe2(p-O)(p-CH3CO2)(tris(pyridin-2-ylmethyl)amine)2](CIO4)3, [Fe(1 ,4,7,10-tetrakis(2- pyridin-2-ylmethyl)-1 ,4,7,10-tetraazacyclododecane)](CIO4)2, [Fe(ll)(1-ethyl-4,7- bis(quinolin-2-ylmethyl)-1 ,4,7-triazacyclononane)CI]CIC>4, [Fe2(p-O)(p-CH3COO) 2,6- bis(pyridin-2-ylmethyl)-1 ,1 ,7,7-tetrakis(pyridine-2-yl)-2,6-diazaheptane](CIO4)4, [Mn(4,11-dimethyl-1 ,4,8,11-tetraazabicyclo[6.6.2]hexadecane)Cl2], [Mn2( -O)2( -
CH3COO)(1 ,2-bis-(4,7-dimethyl-1 ,4,7-triazacyclonon-1-yl)-ethane)]Cl2, [Mn2( -O)( -
CH3COO)2(1 ,4,7-Trimethyl-1,4,7-triazonane)2](PF6)2 and Mn(lll) 5,10,15,20-tetra(4- pyridyl)-21 H,23H-porphine chloride tetrakis(methochloride).
In even more particular embodiments, the iron or manganese complex of use according to the various aspects of the invention is selected from the group consisting of [Fe(dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate)CI]CI, [Fe(N,N-bis(pyridin-2-yl-methyl-1 ,1- bis(pyridin-2-yl)-1-aminoethane)CI]CI, [Fe(N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine)CI]CI, [Fe2(p-O)(p-CH3CC>2)(tris(pyridin-2- ylmethyl)amine)2](CIC>4)3, [Fe(1 , 4,7,10-tetrakis(2-pyridin-2-ylmethyl)-1 , 4, 7,10- tetraazacyclododecane)](CIO4)2, [Fe(ll)(1 -ethyl-4,7-bis(quinolin-2-ylmethyl)-1 ,4,7- triazacyclononane)CI]CIC>4, [Fe2(p-O)(p-CH3COO) 2,6-bis(pyridin-2-ylmethyl)-1 ,1 ,7,7- tetrakis(pyridine-2-yl)-2,6-diazaheptane](CIC>4)4. In yet more particular embodiments, the iron or manganese complex of use according to the various aspects of the invention is selected from the group consisting of [Fe(dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza- bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate)CI]CI, [Fe(N,N-bis(pyridin-2-yl-methyl-1 ,1- bis(pyridin-2-yl)-1-aminoethane)CI]CI, [Fe(N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine)CI]CI, [Fe2(p-O)(p-CH3CC>2)(tris(pyridin-2- ylmethyl)amine)2](CIO4)3 and [Fe2(p-O)(p-CH3COO) 2,6-bis(pyridin-2-ylmethyl)-1 , 1 ,7,7- tetrakis(pyridine-2-yl)-2,6-diazaheptane](CIC>4)4.
Whilst the non-coordinating counterion(s) (corresponding to Y of formula (A1)) and additional coordinating stabilising ligand(s) (corresponding to X of formula (A1)) are specified in the above embodiments, they need not be restricted to those specified and can be readily exchanged for other non-coordinating counterion(s) and coordinating stabilising ligand(s), such as those described above for Y and X of formula (A1). For example, a chloride counterion may be exchanged for a PFe counterion and/or a chloride coordinating stabilising ligand may be exchanged for a coordinating water ligand.
The substrate according to the third aspect of the invention need not be particularly limited and may be any substrate of which treatment with chlorine dioxide is desirable. According to some embodiments, the substrate is, or comprises, a polysaccharide, for example cellulose or starch, often cellulose. An example of a particularly important embodiment in this respect is the treatment of wood pulp. However, a wide variety of other substrates may be treated in accordance with the present invention. For example, the present invention is of broad utility in the treatment of food products, including but not limited to fruit & vegetables, meat and fish; in the treatment of hard surfaces, including but not limited to the sanitation of poultry & animal processing equipment and poultry and animal habitats; and in the treatment of biofilms.
In many of these applications, the aim is sterilisation: by treatment of a food product, for example, including but not limited to fruit, vegetables, meat and fish; a hard surface, such as those of equipment used in food processing (including poultry & animal processing), medical or laboratory equipment and equipment used in poultry and animal husbandry; and biofilms, for example on membranes, the aim is generally to effect sterilisation so as to eradicate or treat microorganisms, such as viruses, bacteria, and protozoa.
The IUPAC definition for biofilms (Pure Appl. Chem., 84(2), 377-410 (2012)) is adopted herein, that is an aggregate of microorganisms in which cells that are frequently embedded within a self-produced matrix of extracellular polymeric substance adhere to each other and/or to a surface. Biofilms are frequently found on membranes present in all types of filtration apparatus. All such membranes are susceptible to fouling with biofilms, particularly those found in reverse osmosis systems. Accordingly, treatment of substrates susceptible to the formation of biofilm is a particularly useful embodiment of the present invention: prevention and/or treatment of biofilms reduces the need for servicing and cleaning, and thus can lead to lower maintenance and system operating costs. As well as equipment such as membranes, equipment susceptible to biofilm formation include, but are not limited to, pipes; cleaning (including laundry, dishwashing and bathing) equipment, such as sinks, baths, showers, dishwashers and washing machines, including the surfaces thereof (e.g. shower room walls and floors); cooling and heating systems; and marine apparatus (including hulls of ships and boats). Often biofilms form in environments frequently or permanently in contact with water. However, it will be understood that this is not necessarily the case, biofilm formation being a significant problem in the oil and gas industry, for example in pipelines and other production equipment.
It is therefore to be understood that the third aspect of the invention is of particular commercial utility in the treatment or prevention of biofilms, the method comprising treating any substrate on which a biofilm may be found, such as the equipment referred to in the previous paragraph.
In addition to the treatment or prevention of biofilms, microbiological control in water can also be achieved by employing the present invention. It is therefore to be understood that the second aspect of the invention is also of particular commercial utility in the treatment of water. In this context, it will be understood that the method according to the third aspect of the invention provides a method of treating water, comprising contacting the water with an amount of a chlorite salt; and a complex as defined herein.
The water that may be treated in accordance with the present invention is not limited. It may be, for example, water in municipal, commercial, industrial and domestic water systems, including drinking water, plant process water, cooling water or water found in swimming pools, boilers, conditioning equipment, or other industrial plant process water.
Although the subsequent discussion focuses on the treatment of cellulosic substrates, and in particular wood pulp (reflecting the commercial reality of the majority of chlorine dioxide usage), it is to be understood that the discussion in this respect is not limiting with the present invention being applicable mutatis mutandis to the treatment of other polysaccharide-containing substrates and indeed the treatment of water as described herein.
According to many embodiments of the invention, the substrate that is treated in accordance with the third aspect of the invention is or comprises a polysaccharide. Within the ambit of polysaccharide-containing substrates, cellulosic (i.e. cellulose- containing) substrates are particularly important commercially. Cellulosic substrates include primarily wood pulp and cotton (and thus cotton -containing material), as well as other plant-derived materials such as bagasse and jute. Treatment of cellulosic substrates is thus widespread, with the bleaching of both wood pulp and cotton being massive industries, cotton being subject to bleaching both in the treatment of raw cotton in the cotton-processing industry and also in laundry (domestic, industrial and institutional). In each case, the objective of the treatment is to bleach these substrates, by which is meant the oxidative removal of undesirable contaminants. In the treatment of raw cotton and wood pulp (and other plant-derived materials), these contaminants are generally polyphenolic materials, with lignin, which is responsible for the dark colour of unbleached wood pulp, comprising a significant proportion of wood. In laundry applications, the undesirable contaminants particularly targeted by bleaching include those responsible for stains.
In order to produce high quality paper grades, wood pulp needs to be delignified and bleached to a sufficient extent to produce white pulp which is also stable towards light- and time-induced yellowing/ageing. Typically, wood is ground, pulped and then treated at high temperatures with alkaline sulfide or sulfite to remove the majority of the lignin. The thus-treated pulp is generally referred to as chemical pulp.
An overview of the use of chlorine dioxide (and other bleaching agents) for wood pulp treatment can be found in Pulp Bleaching, Principles and Practice, C.W. Dence and D.W. Reeve, ed., Tappi, 1996.
Often in a first step, an oxygen delignification process is carried out, to remove about half of the lignin remaining in the chemical pulp. Then, this partly delignified pulp is often treated separately with chlorine dioxide and hydrogen peroxide. Dependent on the type of wood and the paper quality (brightness) desired, up to 2 to 3 separate steps employing chlorine dioxide and 1 to 2 stages with hydrogen peroxide are carried out. Alternatively, delignified and bleached pulp is frequently produced without the use of any chlorine-based bleaching chemicals, resulting in so-called total chlorine free (TCF) pulp.
In the first step after the oxygen delignification step, chlorine dioxide is used mainly as a delignification agent (DO-stage). In some cases, elemental chlorine is also used as a bleaching chemical, which can give good activity in conjunction with chlorine dioxide. Application of chlorine alone (i.e. without chlorine dioxide) is no longer practised, since this can result in the formation of undesirably large amounts of chlorinated waste products. In later stages of the pulp bleaching process (D1 or D2 stages), chlorine dioxide is mainly used to further bleach the pulp, which contains small residues of lignin.
Loadings of chlorine dioxide in pulp mills are typically about 2 to about 10 wt% (with respect to oven-dry pulp), with processing carried out at about 40-100 °C. The duration of the delignification varies but this typically from less than 1 h to 4 h.
It will be understood that the various aspects of the present invention are of utility in each step in wood pulp processing, for example those described above, in which chlorine dioxide may be used.
As noted above, the concentration of the chlorite salt in the aqueous media described herein is about 0.1 to about 50 mM for example about 5 to about 30 mM. The skilled person in the art will be able to optimise the amount required to attain the right level of bleaching or delignification of the wood pulp. The concentration of bleaching chemical, such as chlorine dioxide, is most often expressed in the context of pulp bleaching as kg/ton oven dry pulp (odp). Typical concentrations of chlorine dioxide currently used vary from about 5 to about 20 kg/ton odp. If the pulp is bleached at 10 % consistency level, which means 100 g per kg odp in the bleaching liquor, the concentration of CI02will be about 0.5 to about 2 g/L (which on a molar basis equates to about 7.4 to about 29.4 mM. However, it will be understood that the amount of chlorite salt used in accordance with the present invention may be less than these whilst still retaining the desired extent of bleaching. Of course, the skilled person will be able to determine the appropriate quantity of chlorite salt to use for any given method.
Typically, where the method of the third aspect of the invention is for treating water, the composition of the second aspect, is added into an aqueous solution comprising the water that needs to be treated, for example to achieve antimicrobial activity or to prevent formation of biofilm matter. Whilst the resultant solution may comprise very low levels of chlorine dioxide, such as 1-30 mg/L, the compositions of the invention (such as the composition of the second aspect) may comprise much higher levels of chlorine dioxide, such as 100-5000 mg/L. Typically, the composition of the second aspect will contain about 300 to about 3000 mg/L of chlorine dioxide, the latter value determined by the solubility of chlorine dioxide in water at 25 °C. At lower temperatures, the solubility of chlorine dioxide in water is higher. However, about 3000 mg CIO2/L of water is often prepared. The skilled person will be able to determine the appropriate quantity of chlorine dioxide or chlorite salt to use for any given method.
A further advantage of the present invention, particularly but not necessarily in the context of wood pulp processing arises from the reaction between hypochlorite and chlorite to form chloride and chlorine dioxide. Where aqueous media (e.g. solutions) contain chlorite, this will react with any hypochlorite, which may be formed after reaction of chlorine dioxide with partially oxidised lignin residues (cf Pulp Bleaching, Principles and Practice, C.\N. Dence and D.W. Reeve, ed., Tappi, 1996, at pages 133-138). Hypochlorite as a side product is less desirable as it may react with lignin residues to form chlorinated phenols. However, being a strong oxidant, hypochlorite reacts very efficiently with chlorite to form chloride and chlorine dioxide (cf Z Jia et al., Inorg. Chern., 39(12), 2614-2620 (2000)), and so will react chlorite salt present, preventing hypochlorite reacting further to yield chlorinated side products.
Where used to obtain antimicrobial effect, the amount of chlorite is generally much lower than that used in the context of pulp bleaching, typically about 1 to about 30 mg/l. Again, the skilled person will be able to determine the appropriate quantity of chlorine dioxide or chlorite salt to use for any given method.
In all methods according to the present invention, it will be appreciated that a particular benefit, where chlorite salts are used, is that chlorine dioxide does not need to be generated ex situ.
The aqueous media of the invention has a pH of about 1 to about 3.5. The chlorite salt and complex of the composition of the second aspect may be contacted within an aqueous medium comprising a bisulfate or oxalate buffer, and having a pH of about 1 to about 3.5. Typically, the aqueous media of the invention has a pH of about 1 to about 3.5, more typically about 1.5 to about 3.0. The concentration of the buffer is preferably about 1 mM to about 1 M; more typically about 5 mM to about 50 mM. If, for example, a pH of 2.0 is employed, the pKa of the buffer at the suitable concentration range should be 2.0 +/- 1.0 in order to have effective buffering capabilities. Suitable buffers having low pKa values (about pH 1 to about 3.5) are well known in the art and include bisulfate (HSOT), and oxalic acid. The cationic counterion of the bisulfate buffer can be chosen at will; preferred ones include sodium or potassium cations. For the avoidance of doubt, suitable buffers also act as suitable acids.
Suitable amounts of strong acids having pKa values of less than 1 may also be used (in addition to the buffer) to lower the pH of the aqueous media to the desired level. The skilled person will be able to determine the desired amount of acid to be added by using a pH meter. Examples of suitable strong acids include sulfuric acid, hydrobromic acid and hydrochloric acid. Also, mixtures of different acids may be used, for example a mixture of sodium bisulfate and hydrochloric acid, to further lower the pH of the aqueous media. Mixtures of different acids may be desirable over using only hydrochloric acid (with no buffering capacity at about pH 2) or only sodium bisulfate (where low pH values may difficult to achieve).
The temperature for practice of the methods of the invention may be determined by the skilled person. For example, cellulose treatment processes can be carried out at similar temperatures to those currently practised. Clearly, the optimum temperature will be substrate-dependent, and will often be about 50 to about 70 °C for wood pulp bleaching, although improved bleaching processes have been achieved by increasing the temperature, for example to treat eucalyptus wood pulp. However, it should be noted that the methods described herein may achieve the same bleaching activity at lower temperatures than those achievable absent the iron or manganese complexes described herein. Therefore, whilst the currently used temperature ranges for wood-pulp bleaching are typically about 50 to about 100 °C, use of the iron or manganese complexes described herein may allow these temperatures to be lowered. For the treatment of polysaccharide-based substrates, temperatures of about 30 to about 100 °C are typical, for example about 40 to about 95 °C. For treatment of water or other substrates to attain antimicrobial effect, ambient temperatures (e.g. 15 to 30 °C) are generally appropriate. Nevertheless, it will be appreciated that the exact temperature can be determined without undue burden by those conducting any given method.
Typically, mixing a chlorite salt, an acid comprising bisulfate or hydrogenoxalate with a pKa of about 1 to about 3.5 or an aqueous medium with a bisulfate or oxalate buffer and having a pH of about 1 to about 3.5, and an iron or manganese complex of the invention, such as that of formula (A1), is carried out under ambient conditions, with a preferred temperature of equal to or lower than about 35 °C. There is a preference to avoid exceeding a temperature of about 35 °C, because the solubility of chlorine dioxide in water is lower at higher temperatures (see Deshwal, W and Kundu, N in Asian J. of Chemistry, 27, 4429-4435 (2015)). For this reason, a temperature typically equal to or lower than about 30 °C and more typically equal to or lower than about 25 °C will be employed.
Each and every patent and non-patent reference referred to herein is hereby incorporated by reference in its entirety, as if the entire contents of each reference were set forth herein in their entirety. The invention may be further understood with reference to the following nonlimiting clauses:
Clause 1. A method of generating chlorine dioxide from a chlorite salt, comprising contacting, in an aqueous medium:
(i) the chlorite salt; and
(ii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion, through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms; wherein the aqueous medium comprises a bisulfate or oxalate buffer, and the aqueous medium has a pH of about 1 to about 3.5.
Clause 2. The method according to clause 1 , wherein the pH is about 1.5 to about 3.0.
Clause 3. The method according to clause 1 or clause 2, wherein the aqueous medium comprises a bisulfate buffer.
Clause 4. The method according to any one preceding clause, wherein the aqueous medium contains an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
Clause 5. The method according to clause 4, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid.
Clause 6. The method according to any one preceding clause, wherein the aqueous medium comprises an alkali metal halide.
Clause 7. The method according to clause 6, wherein the alkali metal halide is sodium chloride. Clause 8. The method according to clause 6 or clause 7, wherein the aqueous medium comprises about 10 mM to about 6 M of alkali metal halide.
Clause 9. The method according to clause 8, wherein the aqueous medium comprises about 100 mM to about 1 M of alkali metal halide.
Clause 10. The method of any one preceding clause, wherein the aqueous medium comprises about 0.03 to about 5 pM of the complex.
Clause 11. The method of any one preceding clause, wherein the method involves use of a chlorite salt selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
Clause 12. The method of clause 11 , wherein the chlorite salt is sodium chlorite.
Clause 13. The method of any one preceding clause, wherein the complex is pre-formed.
Clause 14. The method of any one preceding clause, wherein the complex comprises one or more iron ions.
Clause 15. The method of any one preceding clause, wherein the complex comprises a chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms, which is of formula (I), (l-B), (II), (ll-B), (III), (IV), (V), (V-B), (V-C), (VI), (VII), (Vll-B), (VIII), (Vlll-B), or (IX)): wherein: each D is independently selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1 - yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl and thiazol-2-yl, each of which may be optionally substituted by one or more groups independently selected from the group consisting of -F, -Cl, -Br, -OH, -OCi-C4alkyl, -NH-CO-H, -NH-CO-Ci-C4alkyl, -NH2, -NH-Ci-C4alkyl, and -Ci-C4alkyl; the or each R1 and R2 are independently selected from the group consisting of Ci-C24alkyl, Ce-warylCi-Cealkyl, Ce-waryl, and Cs-CwheteroarylCi-Cealkyl, each of which may be optionally substituted by one or more groups selected from -F, -Cl, -Br, -OH, - OCi-C4alkyl, -NH-CO-H, -NH-CO-Ci-C4alkyl, -NH2, -NH-Ci-C4alkyl and -SCi-C4alkyl; and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci.44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci.2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more C i.2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci.2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci.2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci.2oalkyl groups;
R3 and R4 are independently selected from hydrogen, Ci-Csalkyl, Ci-Csalkyl-O- Ci-Csalkyl, Ce-CwaryloxyCi-Csalkyl, Ce-C aryl, Ci-Cshydroxyalkyl, Ce-CwarylCi-Cealkyl and Cs-C heteroarylCi-Cealkyl, and -(CH2)o-4C(0)OR5 wherein R5 is independently selected from: hydrogen, Ci-Csalkyl and Ce- aryl;
Q2 represents a bridge selected from the group consisting of a Ciwalkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ciwalkylene units and one Ce-warylene unit, which bridge is optionally substituted one or more times with independently selected Ci.24alkyl groups and OH groups; and
X is selected from C=O, -[C(R6)2]o-3- wherein each R6 is independently selected from hydrogen, hydroxyl, Ci-C4alkoxy and Ci-C4alkyl;
(II) (H-B) wherein: each Q is independently selected from -CR4R5CR6R7- and -CR4R5CR6R7CR8R9-;
R4, R5, R6, R7, R8, and R9 are independently selected from: H, Ci-C4alkyl and hydroxyCi-C4alkyl; each R1 , R2, and R3 is independently selected from the group consisting of hydrogen, Ci-C24alkyl, CH2CH2OH, CH2COOH, CH2PO3H2, Cs-C heteroarylCi-Cealkyl and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and
Q2 is a bridge selected from the group consisting of a Ci. ealkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ci-salkylene units and one Ce- arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; wherein: each -Q- is independently selected from -N(R)C(RI)(R2)C(RS)(R4)- and -N(R)C(RI)(R2)C(R3)(R4)C(R5)(R6)-; each -Q1- is independently selected from -N(R’)C(RI)(R2)C(R3)(R4)- and -N(R’)C(RI)(R2)C(R3)(R4)C(R5)(R6)-; each R is independently hydrogen or is selected from the group consisting of Ci- C2oalkyl, C2-C2oalkenyl, C2-C2oalkynyl, Ce-C aryl and C7-C2oarylalkyl, each of which may be optionally substituted with Ci-Cealkyl and/or Cs-Cwheteroaryl; and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; the two -R’ groups of the two Q1 groups together form bridging moiety -Q2-;
Q2 is a bridge selected from the group consisting of a C2-6alkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce-C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups; and
Ri-Re are each independently selected from: H, Ci-4alkyl and hydroxyCi.4alkyl;
(V) (V-B) (V-C) wherein: each -R1 is independently selected from -CH2N(Ci-C24alkyl)2, -CH2NR7 or an optionally Ci-Cealkyl-substituted heteroaryl group selected from pyridin-2-yl, pyrazineyl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1-yl, 1 ,2,4-triazol-3-yl and thiazol-2-yl; each -R2 independently represents -R4-R5; each -R3 and each -R6 each independently represents hydrogen, or a group selected from Ci-Cealkyl, Ce-C aryl, Cs-C heteroaryl, Ce-C arylCi-Cealkyl and Cs-C heteroarylCi-Cealkyl, each of which groups may be optionally Ci-Cealkyl- substituted; each -R4- independently represents optionally Ci-Cealkyl-substituted Ci- Cealkylene; each -R5 independently represents an -CH2N(Ci-C24alkyl)2 group, -CH2NR7 or an optionally Ci-Cealkyl-substituted heteroaryl group selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol- 2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl,
1 .2.3-triazol-4-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, and thiazol-2-yl; each -NR7 independently represents a moiety in which R7 and the nitrogen atom N to which it is attached represents a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to R4 through the nitrogen atom N; and
Q2 represents a bridge selected from the group consisting of a Ci-ealkylene moiety Ce- arylene moiety or a moiety comprising one or two Ci-3alkylene units and one Ce- arylene unit, which bridge is optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups;
N(CY2-R1)3 (VI) wherein: each -R1 is independently selected from -CY2N(Ci-C24alkyl)2; -CY2NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci .ealkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; or represents an optionally Ci-Cealkyl- substituted heteroaryl group selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-1-yl, pyrazol-3-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1 -yl,
1 .2.4-triazol-3-yl and thiazol-2-yl; and each Y is independently selected from H, CH3, C2H5, C3H?; R1 R2N-X-NR1 R2 (VII); and R1 R2N-X-NR2(-Q2-R2N)n-X-NR1 R2 (Vll-B); wherein:
-X- is selected from -CY2CY2-, cis- or trans-1 ,2-cyclohexylene, -CY2CY2CY2-, - CY2C(OH)YCY2-, with each Y being independently selected from H, CH3, C2H5 and C3H7; n is an integer from 0 to 10; each R1 group is independently an alkyl, heterocycloalkyl, heteroaryl, aryl, arylalkyl or heteroarylalkyl group, each of which may be optionally substituted with a substituent selected from the group consisting of hydroxy, alkoxy, phenoxy, phosphonate, carboxylate, carboxamide, carboxylic ester, sulfonate, amine, mono- or dialkylamine and N+(R3)s, wherein R3 is selected from hydrogen, alkyl, alkenyl, arylalkyl, arylalkenyl, hydroxyalkyl, aminoalkyl, and alkyl ether; each R2 is independently -CZ2-R4, with each Z being independently selected from H, CH3, C2H5, C3H7; and each -R4 being independently selected from optionally substituted -N(Ci-C24alkyl)2; -NR7, wherein each -NR7 independently represents a moiety in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-ealkyl groups, which is connected to CZ2 through the nitrogen atom N; and an optionally Ci-Cealkyl-substituted heteroaryl group selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin- 2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2- yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, and thiazol-2-yl; and CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and Q2 is a bridge selected from the group consisting of a Ciwalkylene bridge, a Ce- arylene bridge or a bridge comprising one or two Ciwalkylene units and one Ce-w arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups;
(VIII) (Vlll-B) wherein: each Q group independently represents -CY2- or -CY2CY2-, in which each Y is independently selected from hydrogen, Ci-24alkyl, or a Ce- aryl; each D group independently represents a heteroarylene group or a group of the formula -NR-, with the proviso that at least one D group represents a heteroarylene group; each D1 group represents a group of the formula -NR’-; the two -R’ groups of the two D1 groups together form bridging moiety -Q2-;
Q2 is a bridge selected from the group consisting of a Ci-ealkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce- C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; and each R group independently represents H, Ci-24alkyl, Ce- aryl or Cs-wheteroaryl; and
R1-CY2-(NR3)-CY2-R2-CY2-(NR3)-CY2-R1 (IX) wherein: each Y is independently selected from H, CH3, C2H5 and C3H7; each R1 is independently selected from an optionally Ci-Cealkyl-substituted C5- Cwheteroaryl group, whereby the Cs-Cwheteroaryl group is selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1 - yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, and thiazol-2-yl;
R2 is selected from an optionally Ci-Cealkyl-substituted Cs-Csheteroarylene group, whereby the Cs-Csheteroarylene group is selected from pyridin-2,6-diyl, pyrazin- 2,6-diyl, pyrazol-3,5-diyl, pyrazol-1 ,3-diyl, pyrrol-2,5-diyl, imidazol-2,5-diyl, imidazol-1 ,4- diyl, pyrimidin-2,6-diyl, 1 ,2,4-triazol-3,5-diyl, 1 ,2,4-triazol-1 ,3-diyl, 1 ,2,4-triazol-2,4-diyl, 1 ,2,3-triazol-1 ,4-diyl, 1 ,2,3-triazol-2,5-diyl, and thiazol-2,5-diyl; each R3 is independently selected from optionally Ci-Cealkyl-substituted Ci- 24alkyl, Ce- aryl, Ce-ioarylCi-C24alkyl, Cs- heteroaryl, C5-ioheteroarylCi-C24alkyl.
Clause 16. The method of any one of clauses 1 to 14, wherein the complex comprises one or more manganese ions and a porphyrin or porphyrazine ligand of formula (X or (XI): wherein: each R1, R2, R3, and R4 is a 5- to 10-membered N-heteroaryl optionally substituted with one or more selected from the group consisting of Ci-24alkyl, C3- scycloalkyl, C^cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci- 24alkylphenyl, Ci.24alkylnaphthyl, Ci.24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R1a, R2a, R3a and R4a is independently selected from the group consisting of Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci-24alkylphenyl, Ci.24alkylnaphthyl, Ci-24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; and n is 0 to 2; wherein:
A1, A2, A3, A4, B1, B2, B3, B4, C1, C2, C3, C4, D1, D2, D3 and D4 are independently selected from N, C-H, C-Rn, N+-H and N+-Rn with the proviso that no more than one of Ai, Bi, Ci , and Di is N, N+-H or N+-Rn, no more than one of A2, B2, C2, and D2 is N, N+-H or N+-Rn, no more than one of A3, B3, C3, and D3 is N, N+-H or N+-Rn, and no more than one of A4, B4, C4, and D4 is N, N+-H or N+-Rn, and wherein: each Rn is independently selected from Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci-24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci.24alkylphenyl, Ci.24alkylnaphthyl, Ci- 24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R1, R2, R3, and R4 is a 5- to 10-membered N-heteroaryl optionally substituted with one or more selected from the group consisting of Ci-24alkyl, C3- scycloalkyl, C^cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci- 24alkylphenyl, Ci.24alkylnaphthyl, Ci.24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R1a, R2a, R3a and R4a is independently selected from the group consisting of Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci-24alkylphenyl, Ci.24alkylnaphthyl, Ci-24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; and n is 0 to 2. Clause 17. The method of clause 15, wherein the chelant is selected from formula (I), (II), (ll-B), (III), (IV), (V), (V-B), (VI) and (VII), such as (I), (II), (IV), (V), (V-B), (VI) and (VII).
Clause 18. The method of any one of clauses 1 to 14, wherein the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-
3.7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, dimethyl 2,4-di-(2-pyridyl)-3- (pyridin-2-ylmethyl)-7-methyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, dimethyl 9,9-dihydroxy-3-methyl-2,4-di-(2-pyridyl)-7-(1-(N,N-dimethylamine)-eth-2-yl)-
3.7-diaza-bicyclo[3.3.1]nonane-1 ,5-dicarboxylate, dimethyl 2,4-di-(2-pyridyl)-3,7- dimethyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N,N-bis(pyridin-2-yl- methyl-1 , 1 -bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N-(pyridin-2-yl-methyl)- bis(pyridin-2-yl)methylamine, N-benzyl-N-(pyridin-2-yl-methyl)-bis(pyridin-2- yl)methylamine, N-methyl-N,N’,N’-tris(pyridin-2-ylmethyl)ethylenediamine, N-butyl- N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene-diamine, N-octyl-N,N’,N’-tris(pyridin-2- ylmethyl)-1 ,2-ethylene-diamine, N, N, N’, N’-tetrakis(pyridin-2-yl-methyl)ethylene-1 ,2- diamine, N, N, N’, N’-tetrakis(benzimidazol-2-ylmethyl)ethylene-1 ,2-diamine, tris(pyridin- 2-ylmethyl)amine, 1 ,4,7, 10-tetrakis(2-pyridin-2-ylmethyl)-1 ,4,7,10- tetraazacyclododecane, 1-methyl-4,7-bis(pyridin-2-ylmethyl)-1 ,4,7-triazacyclononane,
1-methyl-4,7-bis(quinolin-2-ylmethyl)-1 ,4,7-triazacyclononane, 1 -ethyl-4,7-bis(quinolin-
2-ylmethyl)-1 ,4,7-triazacyclononane, 2,6-bis(pyridin-2-ylmethyl)-1 , 1 ,7,7-tetrakis(pyridin- 2-yl)-2,6- diazaheptane, 2,6-bis(pyridin-2-ylmethyl)-1 , 1 ,7,7-tetrakis(pyridine-2-yl)-2,6- diazaheptane (N,N’-bis(dipyridin-2-ylmethyl)-N,N’-bis(pyridin-2-ylmethyl)-1 ,3-diamino- propane), 1 ,4, 7-trimethyl- 1 ,4,7-triazacyclononane, 4,11-dimethyl-1 ,4,8,11- tetraazabicyclo[6.6.2]hexadecane, and 5,10,15,20-tetra(4-pyridyl)-21 H,23H-porphine tetrakis(methochloride).
Clause 19. The method of any one of clauses 1 to 14, wherein the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-
3.7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N, N-bis(pyridin-2-yl-methyl-1 , 1 - bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine, tris(pyridin-2-ylmethyl)amine, 1 ,4,7, 10-tetrakis(2-pyridin-2- ylmethyl)-1 ,4,7,10-tetraazacyclododecane, 1-ethyl-4,7-bis(quinolin-2-ylmethyl)-1 ,4,7- triazacyclononane and 2,6-bis(pyridin-2-ylmethyl)-1 , 1 ,7,7-tetrakis(pyridine-2-yl)-2,6- diazaheptane. Clause 20. The method of any one of clauses 1 to 14, wherein the chelant is selected from the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-
3.7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N, N-bis(pyridin-2-yl-methyl-1 , 1 - bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N,N’,N’-tris(pyridin-2- ylmethyl)ethylenediamine, tris(pyridin-2-ylmethyl)amine, and 2,6-bis(pyridin-2-ylmethyl)-
1 .1 .7.7-tetrakis(pyridine-2-yl)-2,6-diazaheptane.
Clause 21. The method of any one of clauses 1 to 14, wherein the chelant is dimethyl
2.4-di-(2-pyridyl)-3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-one-
1.5-dicarboxylate.
Clause 22. A composition comprising:
(i) an aqueous medium comprising a bisulfate, or oxalate buffer, and having a pH of about 1 to about 3.5;
(ii) a chlorite salt; and
(iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
Clause 23. The composition of clause 22, wherein the pH is about 1 .5 to about 3.0.
Clause 24. The composition according to clause 22 or clause 23, wherein the aqueous medium is as defined in any one of clauses 3 to 9.
Clause 25. The composition of any one of clauses 22 to 24, wherein the chlorite salt is selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
Clause 26. The composition of clause 25, wherein the chlorite salt is sodium chlorite. Clause 27. The composition of any one of clauses 22 to 27, wherein the complex is as defined in any one of clauses 12 to 21 .
Clause 28. A method of treating water or a substrate comprising contacting the water or the substrate with the composition defined in any one of clauses 22 to 27.
Clause 29. The method of clause 28, wherein the substrate is a cellulosic substrate.
Clause 30. The method of clause 29, wherein the substrate is wood pulp.
Clause 31. A solid composition comprising:
(i) a solid acid comprising bisulfate or oxalate and having a pKa in water at 25°C of about 1 to about 3.5;
(ii) a chlorite salt; and
(iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
Clause 32. The solid composition of clause 31 , wherein the pKa is about 1.5 to about 3.0.
Clause 33. The solid composition according to clause 31 or clause 32, wherein the solid acid comprises a bisulfate buffer.
Clause 34. The solid composition of any one of clauses 31 to 33, which comprises an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
Clause 35. The solid composition of clause 34, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid. Clause 36. The solid composition of any one of clauses 31 to 35, which further comprises an alkali metal halide.
Clause 37. The solid composition of clause 36, wherein the alkali metal halide is sodium chloride.
Clause 38. The solid composition of any one of clauses 31 to 37, wherein the chlorite salt is selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
Clause 39. The solid composition of clause 38, wherein the chlorite salt is sodium chlorite.
Clause 40. The solid composition of any one of clauses 31 to 39, wherein the complex is as defined in any one of clauses 12 to 21 .
Clause 41. A composition comprising a chlorite salt, an acid comprising bisulfate or oxalate, having a pKa in water at 25°C of about 1 to about 3.5 and one or more polydentate ligands, which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms.
Clause 42. The composition of clause 41 , wherein the pKa is about 1.5 to about 3.0.
Clause 43. The composition according to clause 41 or clause 42, which comprises a bisulfate buffer.
Clause 44. The composition of any one of clauses 41 to 43, which comprises an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
Clause 45. The composition of clause 44, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid.
Clause 46. The composition of any one of clauses 41 to 45, which further comprises an alkali metal halide. Clause 47. The composition of clause 46, wherein the alkali metal halide is sodium chloride.
Clause 48. The composition of any one of clauses 41 to 47, wherein the chlorite salt is selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite.
Clause 49. The composition of clause 48, wherein the chlorite salt is sodium chlorite.
Clause 50. The composition of any one of clauses 41 to 49, wherein the polydentate ligands are as defined in any one of clauses 15 to 21 .
Clause 51. A kit comprising, separately:
(i) a chlorite salt;
(ii) an acid comprising bisulfate or oxalate, and having a pKa in water at 25°C of about 1 to about 3.5; and
(iii) one or more polydentate ligands, which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms.
Clause 52. The kit of clause 51 , wherein the chlorite salt is as defined in clause 48 or clause 49.
Clause 53. The kit of clause 51 or clause 52, wherein the pKa is about 1.5 to about 3.0.
Clause 54. The kit according to any one of clauses 51 to 53, wherein the acid comprises a bisulfate buffer.
Clause 55. The kit of any one of clauses 51 to 54, which comprises an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid.
Clause 56. The kit of clause 55, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid. Clause 57. The kit of any one of clauses 51 to 56, which further comprises an alkali metal halide.
Clause 58. The kit of clause 57, wherein the alkali metal halide is sodium chloride.
Clause 59. The kit of any one of clauses 51 to 58, wherein the polydentate ligand is as defined in any one of clauses 15 to 21 .
Clause 60. The kit of any one of clauses 51 to 59, further comprising an iron or manganese salt.
Clause 61 . A kit comprising, separately:
(i) a chlorite salt;
(ii) an acid comprising bisulfate or oxalate, and having a pKa in water at 25°C of about 1 to about 3.5; and either:
(iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or
(iv) a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
Clause 62. The kit of clause 61 , wherein the chlorite salt is as defined in clause 48 or clause 49.
Clause 63. The kit of clause 61 or clause 62, wherein the pKa is about 1.5 to about 3.0.
Clause 64. The kit according to any one of clauses 61 to 63, wherein the acid comprises a bisulfate buffer.
Clause 65. The kit of any one of clauses 61 to 64, which comprises an acid selected from sodium bisulfate, potassium bisulfate, sulfuric acid, hydrochloric acid, oxalic acid, and hydrobromic acid. Clause 66. The kit of clause 65, wherein the acid is selected from sodium bisulfate, potassium bisulfate and hydrochloric acid.
Clause 67. The kit of any one of clauses 61 to 66, which further comprises an alkali metal halide.
Clause 68. The kit of clause 67, wherein the alkali metal halide is sodium chloride.
Clause 69. The kit of any one of clauses 61 to 68, wherein the complex is as defined in any one of clauses 12 to 21 .
The following non-limiting examples below serve to illustrate the invention further.
EXPERIMENTAL
Compound (1): [Fe(N2py3o-C1)CI]CI (N2py3o-C1 = dimethyl 2,4-di-(2-pyridyl) - 3-methyl-7-(pyridin-2-ylmethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate) was obtained as described in WO 02/48301 (Unilever).
Compound (2): [Fe(MeN4py)CI]CI (MeN4py = N,N-bis(pyridin-2-yl-methyl-1 , 1 - bis(pyridin-2-yl)-1 -aminoethane) and MeN4py were prepared as described in EP0909809 (Unilever).
Compound (3): [Fe(Me-trispicen)CI]CI (Me-trispicen=N-methyl-N,N’,N’- tris(pyridin-2-ylmethyl)ethylenediamine) was prepared as published by I Bernal et al ( . Chem. Soc., Dalton Trans, 22, 3667-3675 (1995)).
Compound (4): [Fe2(p-O)(p-CH3CO2)(TPA)2](CIO4)3 (TPA = tris(pyridin-2- ylmethyl)amine) was prepared as described by L. Que et al., J. Am. Chem. Soc., 112, 1554-1562 (1990).
Compound (5): [Fe(CyclenPy4)](CIO4)2 (CyclenPy4= 1 ,4,7, 10-tetrakis(2-pyridin-2- ylmethyl)-1 ,4,7,10-tetraazacyclododecane) was prepared as described by X-H Bu and co-workers, Polyhedron, 19, 431-435 (2000) and 17, 289-293 (1998).
Compound (6): [Fe(ll)(EtQuin2TACN)CI]CIO4 (EtQuin2TACN = 1-ethyl-4,7- bis(quinolin-2-ylmethyl)-1 ,4,7-triazacyclononane) was prepared as described elsewhere (WQ2001/064826).
Compound (7): [Fe2(p-O)(p-CH3COO)L](CIO4)4 (L=2,6-bis(pyridin-2-ylmethyl)- 1 ,1 ,7,7-tetrakis(pyridine-2-yl)-2,6-diazaheptane (N,N’-bis(dipyridin-2-ylmethyl)-N,N’- bis(pyridin-2-ylmethyl)-1 ,3-diamino-propane) has been prepared as described elsewhere (EP1165738B1).
Compound (8): [Mn(Bcyclam)Cl2], (Bcyclam = 4, 11 -dimethyl-1 ,4,8, 11 - tetraazabicyclo[6.6.2]hexadecane) was prepared as described in WO98/39098 and J. Am. Chem. Soc., 122, 2512-2522 (2000).
Compound (9): [Mn2( -O)2( -CH3COO)(Me4-DTNE)]Cl2 (Me4-DTNE = 1 ,2-bis- (4,7-dimethyl-1 ,4,7-triazacyclonon-1-yl)-ethane) was obtained as disclosed in WO 2011/106906 Unilever PLC et al.).
Compound (10): [Mn2( -O)( -CH3COO)2(Me3TACN)2](PF6)2 (Me3TACN = 1 ,4,7- Trimethyl-1 , 4, 7-triazonane) was obtained as described by J.H. Koek eta/, J. Chem. Soc., Dalton Trans., 353-362 (1996).
Compound (11): Mn(lll) 5,10,15,20-tetra(4-pyridyl)-21 H,23H-porphine chloride tetrakis(methochloride) ^^eClsMnNs] was purchased from Merck (Sigma Aldrich).
In all cases, stock solutions of 1 mM of each compound were made (in water, except for compounds (7) and (10), which were dissolved in ethanol). Each stock solution was further diluted in water to a concentration of 0.1 mM. This solution was used to carry out the measurements on the activity of CIO2 formation by each of the compounds, tested in a concentration range of 0.1 to 10 pM in aqueous solutions at a pH of around 2 (see details of concentrations used in each case in the experiments below).
All other chemicals were obtained from the regular chemical suppliers.
COMPARATIVE EXPERIMENT: NaCIOa/pH 5 acetate buffer/compound 1.
A comparative experiment was carried out using 10 pM of compound 1 in an aqueous solution of pH 5 using acetic acid buffer (50 mM) and sodium chlorite (10 mM), which was allowed to react for 1 hr at 25 °C. The formation of CIO2 thus generated could be followed using the absorbance at 359 nm and the extinction coefficient of 1250 M’ 1cnr1 (J. Am. Chem. Soc., 136, 3680-3686 (2014)). After one hour an absorbance of 1.4 at 359 nm was measured, indicating that 1.1 mM of CIO2 had formed. The formation of further CIO2 was observed beyond the 1 hr reaction time, indicating a relatively slow process to form CIO2 under these conditions.
Similar experiments using 5 and 1 pM of compound 1 , yielded concentrations of chlorine dioxide of 0.7 mM and 0.2 mM respectively. The blank (no catalyst) showed virtually no formation of chlorine dioxide. These results show that in acetate buffer pH 5, which has been identified as being suitable to generate chlorine dioxide from sodium chlorite with compound 1 , the formation of chlorine dioxide is indeed proceeding in a catalytic manner, with the rate of formation being dependent on the concentration of the catalyst.
EXPERIMENT 1 : NaCIO2/pH 2 NaHSO4 buffer/compound 1.
First a blank experiment was carried out, using 10 mM NaCIC>2 and 11 mM NaHSC in water at pH 2.32 at 22 °C. The slow formation of chloride dioxide was observed (absorbance of 1.36 at 359 nm after 1 hr, which is equivalent to 1.05 mM chlorine dioxide, based on the extinction coefficient of 1250 M'1cm-1 ( . Am. Chem. Soc., 136, 3680-3686 (2014)).
The same experiment, with 0.1 pM of compound 1 added to the solution yielded a marked acceleration in chloride dioxide formation under the same conditions (1.36 mM chlorine dioxide formed after 1 hr).
Increasing the concentration of compound 1 to 1 pM yielded 2.2 mM CIO2 in the same time period (1 hr), about 1 .36 mM of CIO2 was formed. It should be noted that this is the same amount of chlorine dioxide was formed as without catalyst after 1 hr, indicating a strong acceleration effect of this catalyst to form chlorine dioxide.
Increasing the concentration of compound 1 to 10 pM yielded 2.7 mM CIO2 in 1 hr, which is a slight improvement over using 1 pM of compound 1. After 5 minutes of reaction time under these conditions, the same amount of chlorine dioxide was formed (2.7 mM) as after 1 hr, again indicating a strong acceleration effect of this catalyst to form chlorine dioxide.
Table 1 shows a compilation of the results obtained at different catalyst concentrations. When using 0.1-1 pM of compound 1 , a steady built-up of chlorine dioxide was obtained. Increasing to 5 or 10 pM of compound 1 , leads to the formation of a much higher concentration of chlorine dioxide after 5 minutes than the reference without catalyst after 1 hr reaction time. Table 1. CIO2 formation (in mM) after 300, 780 and 3600 seconds reaction times (pH 2.32, T = 22 °C), using 10 mM NaCIC>2 and 11 mM NaHSC and different concentrations of compound 1.
The amount of chlorine dioxide generated when using 0.1 pM, 5 pM and 10 pM of compound 1 was substantially greater when using a NaHSC buffer at a pH of 2.32 than when using an acetate buffer at a pH of 5 (compare 1.1 mM, 0.7 mM and 0.2 mM of CIO2 generated after 1 hour using 10 pM, 5 pM and 0.1 pM of 1 in an acetate buffer with 2.75 mM, 2.62 mM and 1.63 mM generated after 1 hour using 10 pM, 5 pM and 0.1 pM of 1 in a NaHSC buffer.
EXPERIMENT 2: NaCIC /Various NaHSC concentrations/compound 1.
A similar experiment as described for experiment 1 was carried out, but with reduced amounts of NaHSC in solution.
As shown in Table 2 below, reducing the concentration of sodium bisulfate leads to an increase in the pH of the solution (less acid is added to compensation for the pH increase due to the addition of sodium chlorite).
Without catalyst, there is a clear reduction of CIO2 formation when using 2.8 mM or 1.1 mM sodium bisulfate. Addition of 0.5 or 1 pM of compound 1 leads to a strong increase of the rate of chlorine dioxide formation, even at 4 times lower concentrations of sodium bisulfate than used in experiment 1 .
These results show that the amount sodium bisulfate could be reduced without the loss of activity towards chlorine dioxide formation if a small amount of catalyst is added. Further it is noted that when the pH of the mixture increases to pH 5.77, the activity is getting low (even in the presence of catalyst). Table 2. CIO2 formation (in mM) after 1 h reaction time (T = 22 °C), using 10 mM NaCIC>2 and various concentrations of NaHSO4 and of compound 1. The pH of the solution was determined immediately after mixing NaHSO4 and sodium chlorite in water.
EXPERIMENT 3: NaHSO4/Various NaCIC concentrations/compound 1.
A similar experiment as described above was carried out using reduced amounts of NaCIC>2 in solution. The amount of NaHSO4 used in this experiment was 5.5 mM (which is half the amount used in experiment 1). The results are shown in Table 3.
Table 3. CIO2 formation (in mM) after 1 h reaction time (T = 22 °C), using various concentrations of NaCIC>2, 5.5 mM of NaHSO4 and various concentrations of compound 1. It is observed that, without catalyst, the amount of chlorine dioxide formed is reduced when 4 times less sodium chlorite is used. However, in the presence of compound 1 , even with the lowest level of sodium chlorite, much more chlorine dioxide is measured (independent on starting chlorite concentration and catalyst concentration). EXPERIMENT 4: NaHSO4/HCI/NaCIO2/compound 1.
A similar experiment as described for experiment 3 above was carried out using 10 mM NaCIC>2 and 5.5 mM of NaHSC in solution to which various amounts of HCI was added to reach lower pH values. The resulting pH values, and CIO2 formation after 5 minutes without and with 0.1 pM of compound 1 are given in Table 4 below.
Table 4. CIO2 formation (in mM) after 300 seconds reaction time (T =22 °C), using 10 mM NaCIC>2, 5.7 mM of NaHSC , various concentrations of HCI, without and with compound 1.
It is noted that even after a reaction time of just 5 minutes, the benefit of adding 1 pM of the catalyst is very clearly observed. Adding HCI solution gives some extra CIO2 formation with 1 pM being present.
EXPERIMENT 5: HCI - no buffer/NaCIOa/compound 1.
A similar experiment as described for experiment 4 above was carried out using 10 mM NaCIC>2 and various amounts of HCI without NaHSC present in the solution. The resultant pH values, CIO2 formation after 5 minutes without and with 1 pM of compound 1 are given in Table 5 below.
Table 5. CIO2 formation (in mM) after 300 seconds reaction time (T =22 °C), using various concentrations of HCI in the presence of 10 mM NaCIC>2, without and with compound 1.
In each case, the benefit of adding 1 pM of the bispidon catalyst is very clear. Increasing the amount of acid, leads to, as expected, a lowering of the pH of the mixture. Small amounts of CIO2 are formed after 5 mins (slightly increasing when decreasing the pH), but in the presence of the catalyst, much higher levels of CIO2 form in the same time period. It should be noted that in the presence of 5 or 10 mM of HCI, significantly less CIO2 is formed (in the presence of the catalyst) than in comparable experiment 4, with HCI in the presence of sodium bisulfate.
EXPERIMENT S: NaCIO2/pH 2 NaHSO4 buffer/compounds 2-11.
A series of Mn and Fe complexes (complexes 2-11) were tested in aqueous solutions comprising 11 mM NaHSC buffer and 10 mM NaCIC>2 at pH 2.0, using complex concentrations of 1 or 10 pM. The concentrations of CIO2 formed were analysed after 300 and 780 seconds.
Table 6. CIO2 formation (in mM) after 300 and 780 seconds reaction times (pH 2, T =25 °C), using 10 mM NaCIC>2 and 11 mM NaHSC
* When depicted as > 2.5 mM, it was noted that the absorbance at 359 nm became higher than about 3.
The results of Table 6 show that all of the compounds exemplified accelerate the formation of chlorine dioxide from chlorite at pH 2 in bisulfate buffer. The extent of the chlorine dioxide formed after 300 or 780 s reaction time depends on the catalyst used. Compounds 2-7, compounds 2-4 and 7 in particular, show a strong accelerating effect on the rate of chlorine dioxide formation, even at low concentrations (1 pM). EXPERIMENT ?: NaCIO2/Oxalic acid/compound 1.
The blank experiment was carried out, using 10 mM NaCIC>2 and 10 mM oxalic acid in water at pH 2.0 at 25 °C. A slow formation of chlorine dioxide was observed (absorbance of 0.17 at 359 nm after 1 hr, which is equivalent to 0.14 mM chlorine dioxide, based on the extinction coefficient of 1250 M'1crrr1 (J.Am.Chem.Soc., 136, 3680-3686 (2014)).
The same experiment, with 0.1 pM of compound 1 added to the solution yielded a marked acceleration in chlorine dioxide formation under the same conditions (1.4 absorbance at 359 nm, which is equivalent to 1.1 mM chlorine dioxide formed after 1 hr). Increasing the concentration of compound 1 to 1 pM yielded 2.7 absorbance at 359 nm, which is equivalent to 2.2 mM CIO2 in the same time period (1 hr).
Increasing the concentration of compound 1 to 10 pM yielded absorbance of 2.4 at 359 nm, which is equivalent to 1 .9 mM CIO2 in 1 hr.
Table 7 shows a compilation of the results obtained at different catalyst concentrations. When using 0.1-1 pM of compound 1 , a steady built-up of chlorine dioxide was obtained. Increasing to 10 pM of compound 1 , leads to the formation of a much higher concentration of chlorine dioxide after 5 minutes than the reference without catalyst after 1 hr reaction time or than when using 0.1 or 1 pM of compound 1 . However, after 1 hr, the amount of chlorine dioxide was somewhat lower when using 10 pM of compound 1 than when using 1 pM of compound 1.
Table 7. CIO2 formation (in mM) after 300, 780 and 3600 seconds reaction times (pH 2, T =25 °C), using 10 mM NaCIC>2 and 10 mM oxalate buffer and different concentrations of compound 1.
The amount of chlorine dioxide generated when using 0.1 pM and 10 pM of compound 1 was substantially greater when using an oxalate buffer at a pH of 2 than when using an acetate buffer at a pH of 5 (compare 1.1 mM and 0.2 mM of CIO2 generated after 1 hour using 10 pM and 0.1 pM of 1 in an acetate buffer with 1.9 mM and 1.1 mM generated after 1 hour using 10 pM and 0.1 pM of 1 in an oxalate buffer. EXPERIMENT S: NaCIO2/NaHSO4/NaCI/compound 1.
All the experiments described in this section were carried out in 0.5 cm cuvettes rather than 1.0 cm cuvettes as used in experiments 1 -7 above.
The blank experiment was carried out using 10 mM NaCIC>2, 11 mM NaHSC and 100 mM NaCI in water at pH 2.0 at 25 °C. A significant formation of chlorine dioxide was already observed (absorbance of 0.95 at 359 nm after 1 hr, which is equivalent to 1.5 mM chlorine dioxide, based on the extinction coefficient of 1250 M'1cm-1 (J.Am.Chem. Soc., 136, 3680-3686 (2014)).
The same experiment, with 0.3 pM of compound 1 added to the solution yielded a marked acceleration in chloride dioxide formation under the same conditions (absorbance of 1 .6 at 359 nm after 1 hr, which is equivalent to 2.5 mM of chlorine dioxide formed).
Increasing the concentration of compound 1 to 1 pM yielded an absorbance of 3.0 at 359 nm, which is equivalent to 4.8 mM CIO2 in the same time period (1 hr).
Table 8 shows a compilation of the results obtained at different catalyst concentrations.
Table 8. CIO2 formation (in mM) after 300, 780 and 3600 seconds reaction times (pH 2 T = 25 °C), using 10 mM NaCIC>2, 100 mM NaCI and 11 mM NaHSC and different concentrations of compound 1 . The values in parentheses given in the table below are the concentrations of chlorine dioxide obtained under the same conditions without NaCI added. The experiments were carried out in 0.5 cm cuvettes. This does not affect the CIO2 concentrations calculated.
The amount of chlorine dioxide generated when using 1 pM of compound 1 was substantially greater when using a NaHSC buffer at a pH of 2 in the presence of 100 mM NaCI than in the absence of NaCI (compare 4.8 mM of CIO2 generated after 1 hour using 1 pM of 1 using a NaHSC buffer at a pH of 2 in the presence of 100 mM NaCI with 2.6 mM generated after 1 hour using 1 pM of 1 using a NaHSC buffer at a pH of 2 without added NaCI. EXPERIMENT S: NaCIO2/pH 2 NaHSO4 buffer/compound 1/NaCI
A similar experiment as described for experiment 2 was carried out, but with a fixed amount of NaHSC and with the addition of different amounts of NaCI.
The experiment was carried out at 25 °C in a mixture of 11 mM NaHSC buffer, 10 mM NaCIC>2 at pH 2.0, and with 1 pM of compound 1. The effect of the addition of NaCI was tested. The amount of NaCI was varied between 0 and 1000 mM. The concentrations of CIO2 formed were analysed after 60 minutes. A maximum of 8 mM of CIO2 can be formed when starting from 10 mM chlorite.
Table 9. CIO2 formation (in mM) after 60 minute reaction times (pH 2, T= 25 °C), using 0-1 pM compound 1 , 10 mM NaCIC>2 and 11 mM NaHSC .
The results tabulated in Table 9 show that the presence of NaCI together with compound 1 accelerates the formation of chlorine dioxide from chlorite. The amount of chlorine dioxide formed after a reaction time of one hour increases as the concentration of NaCI increases, up to a NaCI concentration of 600 mM. For amounts of NaCI greater than 600 mM, a plateau in CIO2 formation is reached. It is noted that a maximum concentration of 8 mM of CIO2 can be formed when starting with 10 mM of chlorite.
Where compound 1 was not present, the addition of NaCI has a very slight accelerating effect on the formation of chlorine dioxide from chlorite. However, the effect appears to reach a plateau at a maximum of 100 mM of NaCI - increasing the concentration of NaCI beyond this does not appear to accelerate the formation of chlorine dioxide from chlorite. The CIO2 yield increases from 14% to up to 21%, i.e. by up to 7%, on addition of NaCI. This is far less than the increase in CIO2 yield of from 33% to up to 69%, i.e. by up to 36% and more than double, on addition of both compound 1 and NaCI.
Overall, in the presence of compound 1 and NaCI, such as 100 mM or 200 mM NaCI, the rate and extent of CIO2 formation is significantly higher than in the absence of NaCI or in the absence of compound 1 . The substantial acceleration in CIO2 production when NaCI and compound 1 were combined was an entirely unexpected observation.

Claims

CLAIMS:
1. A method of generating chlorine dioxide from a chlorite salt, comprising contacting, in an aqueous medium:
(i) the chlorite salt; and
(ii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion, through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms; wherein the aqueous medium comprises a bisulfate or oxalate buffer, and the aqueous medium has a pH of about 1 to about 3.5.
2. The method according to claim 1 , wherein the pH is about 1.5 to about 3.0.
3. The method according to claim 1 or claim 2, wherein the aqueous medium further contains an acid selected from hydrochloric acid and hydrobromic acid, such as hydrochloric acid.
4. The method according to any one of claims 1 to 3, wherein the aqueous medium comprises an alkali metal halide, such as sodium chloride, optionally at a concentration of about 10 mM to about 6 M or about 100 mM to about 1 M .
5. The method of any one preceding claim, wherein the complex is pre-formed and/or the aqueous medium comprises about 0.03 to about 5 pM of the complex.
6. The method of any one preceding claim, wherein the method involves use of a chlorite salt selected from the group consisting of sodium chlorite, potassium chlorite, lithium chlorite, calcium chlorite, barium chlorite and magnesium chlorite, such as sodium chlorite.
7. The method of any one preceding claim, wherein the complex comprises one or more iron ions.
8. The method of any one preceding claim, wherein the complex comprises a chelant capable of chelating at least one iron or manganese ion through at least three nitrogen atoms, which is of formula (I), (l-B), (II), (ll-B), (III), (IV), (V), (V-B), (V-C), (VI), (VII), (Vll-B), (VIII), (Vlll-B), or (IX)): wherein: each D is independently selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1 - yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl and thiazol-2-yl, each of which may be optionally substituted by one or more groups independently selected from the group consisting of -F, -Cl, -Br, -OH, -OCi-C4alkyl, -NH-CO-H, -NH-CO-Ci-C4alkyl, -NH2, -NH-Ci-C4alkyl, and -Ci-C4alkyl; the or each R1 and R2 are independently selected from the group consisting of Ci-C24alkyl, Ce- arylCi-Cealkyl, Ce- aryl, and Cs-C heteroarylCi-Cealkyl, each of which may be optionally substituted by one or more groups selected from -F, -Cl, -Br, -OH, - OCi-C4alkyl, -NH-CO-H, -NH-CO-Ci-C4alkyl, -NH2, -NH-Ci-C4alkyl and -SCi-C4alkyl; and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci.44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci.2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more C i.2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci.2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups;
R3 and R4 are independently selected from hydrogen, Ci-Csalkyl, Ci-Csalkyl-O- Ci-Csalkyl, Ce-C aryloxyCi-Csalkyl, Ce-C aryl, Ci-Cshydroxyalkyl, Ce-C arylCi-Cealkyl and Cs-C heteroarylCi-Cealkyl, and -(CH2)o-4C(0)OR5 wherein R5 is independently selected from: hydrogen, Ci-Csalkyl and Ce- aryl;
Q2 represents a bridge selected from the group consisting of a Ci-ealkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ciwalkylene units and one Ce- arylene unit, which bridge is optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; and
X is selected from C=O, -[C(R6)2]o-3- wherein each R6 is independently selected from hydrogen, hydroxyl, Ci-C4alkoxy and Ci-C4alkyl; wherein: each Q is independently selected from -CR4R5CR6R7- and -CR4R5CR6R7CR8R9-;
R4, R5, R6, R7, R8, and R9 are independently selected from: H, Ci-C4alkyl and hydroxyCi-C4alkyl; each R1 , R2, and R3 is independently selected from the group consisting of hydrogen, Ci-C24alkyl, CH2CH2OH, CH2COOH, CH2PO3H2, Cs-C heteroarylCi-Cealkyl and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and
Q2 is a bridge selected from the group consisting of a Ci-ealkylene moiety, a Ce- arylene moiety or a moiety comprising one or two Ci-salkylene units and one Ce- arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups;
(HI) (IV) wherein: each -Q- is independently selected from -N(R)C(RI)(R2)C(RS)(R4)- and -N(R)C(RI)(R2)C(R3)(R4)C(R5)(R6)-; each -Q1- is independently selected from -N(R’)C(RI)(R2)C(R3)(R4)- and -N(R’)C(RI)(R2)C(R3)(R4)C(R5)(R6)-; each R is independently hydrogen or is selected from the group consisting of Ci- C2oalkyl, C2-C2oalkenyl, C2-C2oalkynyl, Ce-C aryl and C?-C2oarylalkyl, each of which may be optionally substituted with Ci-Cealkyl and/or Cs-Cwheteroaryl; and CH2CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-ioaryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(C6-ioarylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; the two -R’ groups of the two Q1 groups together form bridging moiety -Q2-;
Q2 is a bridge selected from the group consisting of a C^alkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce-C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups; and
R1-R6 are each independently selected from: H, Ci-4alkyl and hydroxyCi.4alkyl;
(V) (V-B) (V-C) wherein: each -R1 is independently selected from -CH2N(Ci-C24alkyl)2, -CH2NR7 or an optionally Ci-Cealkyl-substituted heteroaryl group selected from pyridin-2-yl, pyrazineyl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1-yl, 1 ,2,4-triazol-3-yl and thiazol-2-yl; each -R2 independently represents -R4-R5; each -R3 and each -R6 each independently represents hydrogen, or a group selected from Ci-Cealkyl, Ce-C aryl, Cs-C heteroaryl, Ce-C arylCi-Cealkyl and Cs-C heteroarylCi-Cealkyl, each of which groups may be optionally Ci-Cealkyl- substituted; each -R4- independently represents optionally Ci-Cealkyl-substituted C1- Cealkylene; each -R5 independently represents an -CH2N(Ci-C24alkyl)2 group, -CH2NR7 or an optionally Ci-Cealkyl-substituted heteroaryl group selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol- 2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, and thiazol-2-yl; each -NR7 independently represents a moiety in which R7 and the nitrogen atom N to which it is attached represents a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to R4 through the nitrogen atom N; and
Q2 represents a bridge selected from the group consisting of a Ci-ealkylene moiety Ce- arylene moiety or a moiety comprising one or two Ciwalkylene units and one Ce- arylene unit, which bridge is optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; N(CY2-R1)3 (VI) wherein: each -R1 is independently selected from -CY2N(Ci-C24alkyl)2; -CY2NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci .ealkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; or represents an optionally Ci-Cealkyl- substituted heteroaryl group selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-1-yl, pyrazol-3-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-1 -yl, 1 ,2,4-triazol-3-yl and thiazol-2-yl; and each Y is independently selected from H, CH3, C2H5, C3H?;
R1 R2N-X-NR1 R2 (VII); and R1 R2N-X-NR2(-Q2-R2N)n-X-NR1 R2 (Vll-B); wherein:
-X- is selected from -CY2CY2-, cis- or trans-1 ,2-cyclohexylene, -CY2CY2CY2-, - CY2C(OH)YCY2-, with each Y being independently selected from H, CH3, C2H5 and C3H?; n is an integer from 0 to 10; each R1 group is independently an alkyl, heterocycloalkyl, heteroaryl, aryl, arylalkyl or heteroarylalkyl group, each of which may be optionally substituted with a substituent selected from the group consisting of hydroxy, alkoxy, phenoxy, phosphonate, carboxylate, carboxamide, carboxylic ester, sulfonate, amine, mono- or dialkylamine and N+(R3)3, wherein R3 is selected from hydrogen, alkyl, alkenyl, arylalkyl, arylalkenyl, hydroxyalkyl, aminoalkyl, and alkyl ether; each R2 is independently -CZ2-R4, with each Z being independently selected from H, CH3, C2H5, C3H?; and each -R4 being independently selected from optionally substituted -N(Ci-C24alkyl)2; -NR7, wherein each -NR7 independently represents a moiety in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-ealkyl groups, which is connected to CZ2 through the nitrogen atom N; and an optionally Ci-Cealkyl-substituted heteroaryl group selected from the group consisting of pyridin-2-yl, pyrazin-2-yl, quinolin- 2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol-4-yl, benzimidazol-2- yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, and thiazol-2-yl; and CH2N(R10)(R11), wherein N(R10)(R11) is selected from the group consisting of di(Ci-44alkyl)amino; di(Ce-waryl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; di(Ce- arylCi-6alkyl)amino in which each of the aryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; NR7, in which R7 and the nitrogen atom N to which it is attached represent a heterocycloalkyl group optionally substituted with one or more Ci-2oalkyl groups, which is connected to the remainder of R1 through the nitrogen atom N; di(heterocycloalkylCi-6alkyl)amino, in which each of the heterocycloalkyl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and di(heteroarylCi-6alkyl)amino, wherein each of the heteroaryl groups is independently optionally substituted with one or more Ci-2oalkyl groups; and
Q2 is a bridge selected from the group consisting of a Ci-ealkylene bridge, a Ce- arylene bridge or a bridge comprising one or two Ciwalkylene units and one Ce-w arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups;
(VIII) (Vlll-B) wherein: each Q group independently represents -CY2- or -CY2CY2-, in which each Y is independently selected from hydrogen, Ci-24alkyl, or a Ce- aryl; each D group independently represents a heteroarylene group or a group of the formula -NR-, with the proviso that at least one D group represents a heteroarylene group; each D1 group represents a group of the formula -NR’-; the two -R’ groups of the two D1 groups together form bridging moiety -Q2-;
Q2 is a bridge selected from the group consisting of a Ci-ealkylene moiety, a Ce- arylene moiety, or a moiety comprising one or two Ci-Csalkylene units and one Ce- C arylene unit, which bridge may be optionally substituted one or more times with independently selected Ci-24alkyl groups and OH groups; and each R group independently represents H, Ci-24alkyl, Ce- aryl or Cs-wheteroaryl; and
R1-CY2-(NR3)-CY2-R2-CY2-(NR3)-CY2-R1 (IX) wherein: each Y is independently selected from H, CH3, C2H5 and C3H7; each R1 is independently selected from an optionally Ci-Cealkyl-substituted C5- Cioheteroaryl group, whereby the Cs-C heteroaryl group is selected from pyridin-2-yl, pyrazin-2-yl, quinolin-2-yl, pyrazol-3-yl, pyrazol-1-yl, pyrrol-2-yl, imidazol-2-yl, imidazol- 4-yl, benzimidazol-2-yl, pyrimidin-2-yl, 1 ,2,4-triazol-3-yl, 1 ,2,4-triazol-1-yl, 1 ,2,3-triazol-1 - yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, and thiazol-2-yl;
R2 is selected from an optionally Ci-Cealkyl-substituted Cs-Ceheteroarylene group, whereby the Cs-Ceheteroarylene group is selected from pyridin-2,6-diyl, pyrazin- 2,6-diyl, pyrazol-3,5-diyl, pyrazol-1 ,3-diyl, pyrrol-2,5-diyl, imidazol-2,5-diyl, imidazol-1 ,4- diyl, pyrimidin-2,6-diyl, 1 ,2,4-triazol-3,5-diyl, 1 ,2,4-triazol-1 ,3-diyl, 1 ,2,4-triazol-2,4-diyl, 1 ,2,3-triazol-1 ,4-diyl, 1 ,2,3-triazol-2,5-diyl, and thiazol-2,5-diyl; each R3 is independently selected from optionally Ci-Cealkyl-substituted Ci- 24alkyl, Ce- aryl, Ce-ioarylCi-C24alkyl, Cs- heteroaryl, C5-ioheteroarylCi-C24alkyl.
9. The method of any one of claims 1 to 6, wherein the complex comprises one or more manganese ions and a porphyrin or porphyrazine ligand of formula (X or (XI): wherein: each R1, R2, R3, and R4 is a 5- to 10-membered N-heteroaryl optionally substituted with one or more selected from the group consisting of Ci-24alkyl, C3- scycloalkyl, C^cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci- 24alkylphenyl, Ci.24alkylnaphthyl, Ci.24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R1a, R2a, R3a and R4a is independently selected from the group consisting of Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci-24alkylphenyl, Ci.24alkylnaphthyl, Ci-24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; and n is 0 to 2; wherein:
A1, A2, A3, A4, B1, B2, B3, B4, C1, C2, C3, C4, D1, D2, D3 and D4 are independently selected from N, C-H, C-Rn, N+-H and N+-Rn with the proviso that no more than one of Ai, Bi, Ci , and Di is N, N+-H or N+-Rn, no more than one of A2, B2, C2, and D2 is N, N+-H or N+-Rn, no more than one of A3, B3, C3, and D3 is N, N+-H or N+-Rn, and no more than one of A4, B4, C4, and D4 is N, N+-H or N+-Rn, and wherein: each Rn is independently selected from Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci-24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci.24alkylphenyl, Ci.24alkylnaphthyl, Ci- 24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; each R1a, R2a, R3a and R4a is independently selected from the group consisting of Ci-24alkyl, Cs-scycloalkyl, C4-8cycloalkenyl, Ci.24alkenyl, phenyl, naphthyl, Ci.24alkynyl and Ci-24alkylphenyl, Ci.24alkylnaphthyl, Ci-24alkoxy and phenoxy, each of which may be optionally substituted with one or more selected from the group consisting of Ci-ealkyl, halo and Ci-ehaloalkyl; and n is 0 to 2.
10. The method of claim 8, wherein the chelant is selected from:
(i) formula (I), (II), (ll-B), (III), (IV), (V), (V-B), (VI) and (VII), such as (I), (II), (IV), (V), (V-B), (VI) and (VII); or (ii) the group consisting of dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2- ylmethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, dimethyl 2,4-di-(2- pyridyl)-3-(pyridin-2-ylmethyl)-7-methyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5- dicarboxylate, dimethyl 9,9-dihydroxy-3-methyl-2,4-di-(2-pyridyl)-7-(1-(N,N- dimethylamine)-eth-2-yl)-3,7-diaza-bicyclo[3.3.1]nonane-1 ,5-dicarboxylate, dimethyl 2,4-di-(2-pyridyl)-3,7-dimethyl-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate, N,N-bis(pyridin-2-yl-methyl-1 ,1-bis(pyridin-2-yl)-1 -aminoethane, N-methyl-N-(pyridin-2- yl-methyl)-bis(pyridin-2-yl)methylamine, N-benzyl-N-(pyridin-2-yl-methyl)-bis(pyridin-2- yl)methylamine, N-methyl-N,N’,N’-tris(pyridin-2-ylmethyl)ethylenediamine, N-butyl- N,N’,N’-tris(pyridin-2-ylmethyl)-1 ,2-ethylene-diamine, N-octyl-N,N’,N’-tris(pyridin-2- ylmethyl)-1 ,2-ethylene-diamine, N, N, N’, N’-tetrakis(pyridin-2-yl-methyl)ethylene-1 ,2- diamine, N, N, N’, N’-tetrakis(benzimidazol-2-ylmethyl)ethylene-1 ,2-diamine, tris(pyridin- 2-ylmethyl)amine, 1 ,4,7, 10-tetrakis(2-pyridin-2-ylmethyl)-1 ,4,7, 10- tetraazacyclododecane, 1-methyl-4,7-bis(pyridin-2-ylmethyl)-1 ,4,7-triazacyclononane,
1-methyl-4,7-bis(quinolin-2-ylmethyl)-1 ,4,7-triazacyclononane, 1 -ethyl-4,7-bis(quinolin-
2-ylmethyl)-1 ,4,7-triazacyclononane, 2,6-bis(pyridin-2-ylmethyl)-1 , 1 ,7,7-tetrakis(pyridin- 2-yl)-2,6- diazaheptane, 2,6-bis(pyridin-2-ylmethyl)-1 , 1 ,7,7-tetrakis(pyridine-2-yl)-2,6- diazaheptane (N,N’-bis(dipyridin-2-ylmethyl)-N,N’-bis(pyridin-2-ylmethyl)-1 ,3-diamino- propane), 1 ,4, 7-trimethyl- 1 ,4,7-triazacyclononane, 4,11-dimethyl-1 ,4,8,11- tetraazabicyclo[6.6.2]hexadecane, and 5,10,15,20-tetra(4-pyridyl)-21 H,23H-porphine tetrakis(methochloride), such as dimethyl 2,4-di-(2-pyridyl)-3-methyl-7-(pyridin-2- ylmethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-one-1 ,5-dicarboxylate.
11. A composition comprising:
(i) an aqueous medium comprising a bisulfate, or oxalate buffer, and having a pH of about 1 to about 3.5;
(ii) a chlorite salt; and
(iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
12. A method of treating water or a substrate comprising contacting the water or the substrate with the composition defined in claim 11, optionally wherein the substrate is a cellulosic substrate, for example wood pulp.
13. A solid composition comprising:
(i) a solid acid comprising bisulfate or oxalate and having a pKa in water at 25°C of about 1 to about 3.5;
(ii) a chlorite salt; and
(iii) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
14. A composition comprising a chlorite salt, an acid comprising bisulfate or oxalate, having a pKa in water at 25°C of about 1 to about 3.5 and one or more polydentate ligands, which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms.
15. A kit comprising, separately:
(i) a chlorite salt;
(ii) an acid comprising bisulfate or oxalate, and having a pKa in water at 25°C of about 1 to about 3.5; and either:
(iii) one or more polydentate ligands, which are chelants capable of chelating at least one iron or manganese ion through at least three nitrogen atoms, optionally further comprising an iron or manganese salt; or
(iv) a complex comprising one or more iron ions and one or more polydentate ligands, which are chelants capable of chelating at least one iron ion through at least three nitrogen atoms with the proviso that the one or more polydentate ligands are not porphyrin or porphyrazine ligands; or a complex comprising one or more manganese ions and one or more polydentate ligands, which are chelants capable of chelating at least one manganese ion through at least three nitrogen atoms.
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