MXPA98003444A - Water soluble cross-linking agents - Google Patents

Abstract

Un agente de enlazamiento químico formado de un compuesto fotoactivable di-funcional o superior y que proporciona al menos un grupo que se carga bajo las condiciones de uso, a fin de proporcionar mejorada solubilidad en agua. El agente de enlazamiento además proporciona dos o más grupos fotoactivables para permitir que el agente se emplea como agente de entrelazamiento en sistemas acuosos. El grupo cargado puede proporcionarse por un radical que incluye una o más sales deácidos orgánicos, compuestos onio o aminas protonadas (y opcionalmente uno o más grupos fotorreactivos adicionales), y los grupos fotorreactivos pueden proporcionarse por dos o más radicales que incluyen una aril cetona.

Description

TECHNICAL FIELD OF FIELD SURVEILLANCE AGENTS The present invention relates to chemical and / or physical modification of the surface properties of important substrates from an industrial and medical point of view. In a further aspect, the present invention relates to the various processes useful for modifying the surface properties of bulk materials for specific applications. In this regard, the present invention relates to surface modification techniques such as plasma deposition, radiation grafting, photopolymerization grafting, ion implantation, and chemical derivatization. The present invention further relates to photoactivatable crosslinking agents for use in linking chemical agents to other compounds and / or to a substrate surface. BACKGROUND OF THE INVENTION The chemical modification of surfaces to achieve desired chemical and / or physical characteristics has been previously described. The Patents of the U.S.A. Nos. 4,722,906; 4,973,493; 4,979,959; and 5,002,582 (the descriptions of each of which are incorporated herein by reference), for example, refer to surface modification by the use of latent reactive groups to achieve covalent coupling of reagents such as biomolecules and synthetic polymers to various substrates. The preferred latent reactive group is typically described as a photochemically reactive functional group (i.e., photoreactive group). When exposed to an appropriate energy source, a photoreactive group is subjected to a transformation from an inactive state (ie, basal state) to a reactive intermediate capable of forming covalent bonds with appropriate materials. These latent reactive groups can be used to first derivatize a desired compound (eg, thermochemically), followed by the photochemical connection of the derivatized compound to a surface. This sequential approach is suitable in many situations, but may lack attributes such as speed, versatility, and ease of use, particularly when used with target molecules that are inherently difficult to derivatize first. Latent reactive groups can also be used to prepare photoactivatable heterobifunctional molecules as ligand or bonding agents, for example having a photoreactive group at one end with a thermochemical connection group at the other. (See, for example, the aforementioned Patent '582, and Reiner et al.). These linking agents can be used either to connect non-reactive compounds to a surface or to prime a relatively inert surface in order to render it reactive upon exposure to convenient actinic radiation. The U.S. Patent No. 5,414,075, commonly owned by the assignee of the present application, describes the use of bonding agents to prime a surface in order to provide the surface with photoactivatable groups. This patent describes a multifunctional restricted reagent useful for priming a support surface, or for simultaneous application with a target molecule with a support. Reagents such as those described above, including those described in the '075 patent, are generally hydrophobic. As a result, they are of relatively low solubility in aqueous systems, thus, often limiting their utility in hydrophobic applications. In turn, the binding agents of the prior art are rarely, if at all, coated in compositions employing water as a primary solvent (eg, greater than about 50% by volume). In a separate matter, the preparation and use of a class of cationic polyelectrolytes is described, for example, in "Polyamines and Polyquaternary Ammonium Salts" (pp. 761 763, in Concise Encyclopedia of Polymer Science and Engineering. (Concise Encyclopedia of Polymer Science and Engineering), Kroschwitz, ed., John Wiley & amp;; Sons, 1990, the description of which is incorporated herein by reference. These polyamines and "policuats" are described as being useful in virtue of their cationicity in applications involving interactions with anionically charged colloidal particles in aqueous medium of nature. They are used, for example, in the flocculation of particulate matter from turbid natural waters, as auxiliaries for pigment retention in papermaking, and as filtration aids, agents for breaking emulsion, and so on. Applicants are not aware of the existence of a photoactivatable non-polymeric binding agent, which has both improved aqueous solubility and the ability to bind or bind otherwise non-reactive molecules to a surface. COMPENDIUM OF THE INVENTION The present invention provides a chemical bonding agent comprising a bifunctional or higher photocatalysable charged compound. The binding agent of the invention provides at least one group that is charged under the conditions of use in order to provide improved water solubility. The agent further provides two or more photoactivatable groups in order to allow the agent to be used as an entanglement agent in aqueous systems. In a preferred embodiment, the charge is provided by the inclusion of one or more quaternary ammonium radicals, and the photoreactive groups as provided by two or more radicals of an arylketone such as benzophenone. In a preferred embodiment, the invention provides a linking agent of the general formula: X - Y - X wherein each X, independently, is a radical containing a photoreactive group and Y is a radical containing, inter alia, one or more groups loaded. In such embodiment, the number and / or type of the charged group (s), is sufficient to provide the molecule with sufficient aqueous solubility, to allow the agent to be used (i.e., applied to a surface and activated) in a solvent system that has water as a main component. In a particularly preferred embodiment, Y contains one or more nitrogen-copying groups (e.g., quaternary ammonium). More preferably Y contains a linear or heterocyclic radical, selected from the group consisting of: R3 R3 R3 I q, '- + M l - - R1 - N - R1 - N - R1 1 R2 R? R? R3 R3 R3 R3 Ri - N - Ri - | JJ R? - N - R < - fj- 'R2 R * R2 R2 wherein each R1 independently is a radical containing an alkylene, oxyalkylene, cycloalkylene, arylene or aralkylene group, each R2 independently is a group containing an alkyl, oxyalkyl, cycloalkyl, aryl or aralkyl, and each R3 independently is already a pair not electron ligand, a hydrogen atom, or a radical of the same definition as R2, wherein the groups R1, R2 and R3 may contain heteroatoms that do not interfere such as 0, N, S, P and the like, and / or substituents which are not interference such as halo (for example, Cl) and the like. In a preferred embodiment, one or more of the radicals R 2 contains an aralkyl group in the form of a photoactivatable aryl ketone. These groups, in addition to the two photoactivatable groups that are provided by the X groups defined above, can be used to provide the "trifoto", "tetrafoto" and higher order photoactivatable groups described herein. The use of three or more total photoreactive groups provides the binding agent with the greatest ability to interweave the agent with a target molecule and / or a surface. In another preferred embodiment, the groups R2 and R3 of the above linear radicals can in fact be fused (for example, an R2 and an R3 in a single N atom, or a convenient combination of R2 / R3 groups in adjacent N atoms) in order to form heterocyclic structures different from those exemplified above. The selection and specific relationship between the R groups in a linking agent of the present invention is not critical, as long as the linking agent provides two or more photoactivatable groups and retains sufficient water solubility for its intended use. The term "non-interfering" shall refer to groups, heteroatoms or substituents, the presence of which does not prevent the photoactivatable linking agent from being used for its intended purpose. The binding agent of the present invention has broad applicability, particularly since it can be employed in entanglement applications where prior binding agents have not been effective. In particular, the presence of one or more charged groups (eg, salts of organic acids, onium compounds or protonated amines) provides the agent with improved water solubility. As a result, the binding agents of the invention can be used in aqueous systems that require agents with improved water solubility. This, in turn, provides an effective cost method for the immobilization of inexpensive non-photoreactive molecules on a surface. Since the binding agents themselves can be prepared from inexpensive raw materials, such as amines and bromomethylbenzophenone (BMBP), the final cost of preparing and using these binding agents can be significantly lower than conventional photoreactive agents. The binding agents of the present invention can be employed to simultaneously immobilize (e.g., by interlacing) otherwise non-reactive molecules on a surface. The agents can also be used to prepare a primed latent reactive surface, which can be used for the subsequent application of a target molecule. DETAILED DESCRIPTION As used in the present application, the following words and terms will have the meanings ascribed below: "Water soluble" will refer to a linking agent of the present invention having sufficient solubility to allow it to be used effectively under watery and "(Mono, di, etc.) photo- (Mono, di, etc.) load" shall be used as an abbreviated reference to refer to the total number of photoreactive groups and the total number and type of groups loaded in an agent. link of this invention. For example, "Difoto-Dicuat" shall mean a linking agent of the present invention having two photoreactive groups and two quaternary ammonium groups, examples of which include, but are not limited to those shown in Formulas II to V of Table I. As other examples, "Trifoto-Tricuat" shall mean a linking agent of the present invention having three photoreactive groups and three quaternary ammonium groups (for example of Formula IV); and "Difoto-Monosulfonate" shall mean a linking agent having two photoreactive groups and a sulfonate group (e.g., Formula X); and so on. In a preferred embodiment, the invention provides a linking agent of the general Formula: X-Y-X wherein each X independently is a radical containing a photoreactive group and Y is a radical containing one or more charged groups. RADICAL CONTAINING CHARGE "Y" The linking compound of the present invention includes one or more charged groups, and optionally one or more additional photoreactive groups included in the radical identified in the empirical formula as "Y". A "charged" group, when used in this sense, refers to groups that are present in ionic form, that is, they transpose an electrical charge under the conditions of use (e.g., pH). Charging groups are present, in part, to provide the compound with the desired water solubility. Preferred groups Y are non-polymeric, that is, they are not formed by polymerization of any combination of monomers. Non-polymeric binding agents are preferred since they will tend to have lower molecular mass, which in turn means that in general they can be prepared to have a higher concentration of photoreactive groups per unit mass. In turn, they can generally provide a higher coating density of photoreactive groups than comparable photoreactive polymeric agents (eg, the PVP photo reagents described in the '582 patent described above). The type and number of groups charged in a preferred binding agent are sufficient to provide the agent with a solubility in water (water at room temperature and optimum pH) of at least about 0.1 mg / ml, and preferably at least about 0.5 mg / ml, and more preferably at least about 1 mg / ml. Given the nature of the surface coating process, the solubility levels of the binding agent of at least about 0.1 mg / ml, are generally adequate to provide useful coatings of target molecules on surfaces. This can be contrasted with binding agents in the art, which are typically considered insoluble in water (for example, they have a comparable water solubility in the range of about 0.1 mg / ml or less, and more often about 0.01 mg / ml or less) . For this reason, conventional binding agents are typically provided and used in solvent systems where water is either absent or is provided as a minor component (ie <50% by volume). Examples of suitable charged groups include, but are not limited to, salts of organic acids (such as sulfonate, phosphonate, and carboxylate group), onium compounds (such as quaternary ammonium, sulfonium, and phosphonium groups), and protonated amines, as well as your combinations An example of a linking agent, which employs charged groups other than quaternary ammonium compounds, is provided in Formula X of Table I. By reference to the empirical formula given above, it can be seen that R3 in Formula X would be a lone pair of electrons in order to provide a tertiary amine group, and R2 will contain a charged sulfonate group in a radical of the Formula -CH2-CH2-S03Na. Sufficient total charge to make the compound soluble in water, is provided by the negative charge of the remote sulfonate group. A preferred charged group for use in preparing binding compounds of the present invention is a quaternary ammonium group. The term "quaternary ammonium", as used herein, refers to organic NH4 * derivatives wherein the hydrogen atoms are each replaced by radicals, thereby imparting a net positive charge on the radical. The remaining counter ion may be provided by any convenient anionic species, for example as a chloride, bromide, iodide or sulfate ion. "X" PHOTOREACTIVE GROUPS In a preferred embodiment, two or more photoreactive groups are provided by the X groups connected to the central Y-radical. Upon exposure to a convenient light source, each of the photoreactive groups is subjected to activation. The term "photoreactive group" as used herein, refers to a chemical group that responds to an external energy source applied in order to undergo generation of active species, resulting in covalent attachment to an adjacent chemical structure (e.g. hydrogen exible). Preferred X-groups will be sufficiently photoreactive to provide a visual indication of entanglement in a standardized evaluation of the following type (where additional experimental conditions are given in the Examples below). A solution containing binding agent of the present invention is used to prepare a coating solution with water or water / solvent system as described herein, the solution having a binding agent concentration between 0.1 to 1 mg / ml. Reactive-grade polyvinyl pyrrolidone ("PVP", molecular weight MW approximately 1.5 million daltons), such as that identified as Kollidon 90F ("K 90F") and available from BASF Corporation, is added to the coating solution to achieve a concentration Final PVP of approximately 20 mg / ml, and the resulting composition used to coat on the surface of a polystyrene strip. The composition of the coating is then exposed for about 4 minutes, in situ, to a convenient light source such as a lamp that provides an exposure wavelength of between 250 nm and 450 nm, with an intensity of at least about 1.5 mwatts / cm cvuadrado in the range of wavelength required to promote hydrogen extraction. The existence of coated PVP (ie, entangled with the bonding agent to the polystyrene surface) can be determined qualitatively by spotting with Congo Red (Sigma) After intense washing under a flow of deionized water ("DI") and rubbing, the PVP presence bound on the surface is verified by staining with a solution 0. 35% Congo Red in DI water. Preferred groups are stable enough to be stored under conditions in which they retain these properties. See, for example, U.S. Pat. No. 5,002,582, the description of which is incorporated herein by reference. Latent reactive groups can be chosen that respond to various portions of the electromagnetic spectrum, with those that respond to ultraviolet and visible portions of the spectrum (here referred to as "photoreactive") are particularly preferred. Photoreactive aryl ketones are preferred, such as acetophenone, benzophenone, anthraquinone, antroine, and anthrone heterocycles (ie, heterocyclic anthrone analogs such as those having N, 0, or S at position 10), or their substituted derivatives ( for example, substituted in ring). The functional groups of this ketone are preferred since they are readily capable of undergoing the activation / inactivation / reactivation cycle described herein. Benzophenone is a particularly preferred photoreactive group, since it is capable of photochemical excitation with the initial formation of an excited singlet state that undergoes intersystem crossing to the triplet state. The excited triplet state can be inserted into carbon-hydrogen bonds by extraction of a hydrogen atom (e.g., of a support surface or target molecule in the solution and in proximity of binding to the agent), thereby creating a radical pair. A subsequent crushing of the radical pair leads to the formation of a new carbon-carbon bond. If a reactive bond (eg, carbon-hydrogen) is not available for binding, the ultraviolet-induced excitation of the benzophenone group is reversible and the molecule returns to the basal state energy level upon removal of the energy source, therefore , photoreactive aryl ketones, are particularly preferred. Preparation of Linking Agents The binding agents of the present invention can be prepared using available reagents and chemical conversions within the skill of those in the relevant art. For example, quaternary ammonium salts can be prepared by reaction of tertiary amines with alkyl halides using the Menschutkin reaction (Z. Physik, Chem. 5, 589 (1890)). The reaction rates of these conversions can be improved by the use of highly nucleophilic tertiary amines, together with alkyl halides having easily displaceable halide anions. Typically, the reactivity order is I ">; Br "> Cl", with primary halides and other highly reactive compounds such as benzyl halides preferred for the reaction. The synthesis of iodide of benzyltrimethylammonia, described in Organic Synthesis Collective Volume IV, 585 (1963), is a representative example of this reaction mechanism. Higher order di-, tri- or quaternary ammonium compounds of the invention can be prepared, for example, by reaction of 4-bromomethylbenzophenone ("BMBP") with compounds containing two or more tertiary amine groups. Specific examples of these amines include, but are not limited to, N, N, N ", N ', tetramethylenediamine, N, N, N', N '-tetramethyl-1,6-hexanediamine, N, N, N', N ' , N "pentamethylene-ethylenetriamine, and 1,4-dimethylpiperazine. Table I shows examples of preferred photoactivatable binding agents of the present invention. or r-t i OJ ro OJ • r W O JJ ca cu p a. B or u "faith ? n or H TABLE I (CONT.) Composite Formula TABLE I (CONT.) Formula Compound Annotation Example VI Trifoto 3f3r "Tricuat VII Difoto Monocuat 15 TABLE I (CONT.) Formula Compound Annotation Example II Tetrafoto Tetracuat Tetrafoto Dicuat 15 TABLE I (CONT.) Formula Compound Annotation Example X Difoto 10 ato Use of Linking Agents Linking agents can be used in any convenient way, including by the simultaneous or sequential connection of a chemical compound to a surface. The binding agents of the present invention can be used to modify any convenient surface. When the latent reactive group of the agent is a photoreactive group of the preferred type, it is particularly preferred that the surface provide extractable hydrogen atoms suitable for covalent attachment to the activated group. Plastics such as polyolefins, polystyrenes, poly (methyl) methacrylates, polyalkyl nitriles, poly (vinylacetates), poly (vinyl alcohols), chlorine-containing polymers such as poly (vinyl chloride), polyoxymethylenes, polycarbonates, polyamides, polyimides, phenolic polyurethanes , amino-epoxy resins, polyesters, silicones, cellulose-based plastics and rubber-type plastics, all can be used as supports, providing surfaces that can be modified as described herein. See in general, "Plastics" ("plastics"), pp. 462 464, in Concise Encyclopedia of Polymer Science and Engineering. (Concise Encyclopedia of Polymer Science and Engineering). Kroschwitz, ed., John Wiley & Sons, 1990, the description of which is incorporated herein by reference.

In addition, supports such as those formed of silylated surfaces and pyrolytic carbon of glass, ceramic, or metal are suitable for surface modification. Suitable target molecules for use in the present invention, for connecting to a support surface, comprise a diverse group of substances. Target molecules can be used, either in a non-derivatized or previously derivatized form. Furthermore, target molecules can be immobilized alone or in combination with other types of target molecules. Target molecules can be immobilized to the surface, either after (sequentially) the surface has been primed with the bonding agent. Preferably, however, target molecules are immobilized during (for example simultaneously with) connection of the binding agent present to the surface. Typically, target molecules are chosen in such a way as to confer particularly desired properties on the surface and / or the device or article containing the surface. Examples of suitable target molecules, and the surface properties typically used to provide, are represented by the following non-limiting list: MOLECULA OBJECTIVE FUNCTIONAL ACTIVITY Polymers Synthetic Polyacrylamide substituted Lubricity, surface with sulfonic acid negatively charged, hydrophilicity Polyacrylamide Lubricity, protein repulsion, hydrophilicity Polyethylene glycol Lubricity, cell and protein repulsion, hydrophilicity Polyethyleneimine Positively charged surface Polylactic acid Bioerodable surface Polyvinyl alcohol Lubricity, hydrophilicity Polyvinyl pyrrolidone Lubrication, hydrophilicity Polyacrylamide substituted Lubricity, surface with positively charged quaternary amine Silicone Lubricity, hydrophobicity Conductive Polymers Electric Conductivity (for example, polyvinylpyridine polyacetylene, polypyrrole) Carbohydrates Alginic acid Lubricity, hydrophilicity Cellulose Lubricity, hydrophilicity, source of biodegradable glucose Chitosan Positively charged surface hydrophilicity Glycogen Hydrophilicity, source of biodegradable glucose Heparin Antithrombogenicity, hydrophilicity, cellular connection Ialuronic acid Lubricity , negatively charged surface Pectin Lubricity, hydrophilicityMono-, di-saccharides Hydrophilicity Dextrone sulfate Chromatography medium Proteins Antibodies Antigen binding Antithrombotic agents (for example antithrombin III) Antithrombogenic surface Albumin Non-thrombogenic surface Proteins / connection peptides Cell connection (eg collagens) Enzymes Catalytic surfaces Proteins / matrix peptides Cell and extracellular growth connection Growth factors Cell growth Proteins / peptides Hirudin Antithrombogenic surface Thrombolytic proteins Thrombolytic activity (eg, streptokinase, plasmin, urokinase) Lipids Fatty acids Hydrophobicity, biocompatibility Mono-, di- and triglycerides Hydrophobicity, biodegradable lubricity, source of fatty acid Phospholipids Hydrophobicity, lubricity, biodegradable source of fatty acid Prostaglandins / leukotrienes Messengers immobilized / non-thrombogenic surface Nucleic acids DNA Substrate for affinity / nucleases binding RNA Substrate for affinity binding / nucleases Nucleosides, nucleotides Source of purines, pyrimidines, enzyme cofactors Drugs / vitamins / cofactors Enzyme co-factors Immobilized enzymes Heme compounds U nions of globin / surface oxygenation Drugs Drug activity Non-polymeric materials Dyes (eg azo dyeing agents) Fluorescent compounds Fluorescence (eg fluorescein) Any convenient technique can be used for connecting a bonding agent to a surface, and these techniques can be selected and optimized for each material, process or device. The bonding agent can be successfully applied to clean surfaces of materials as listed above by spraying, dipping or brushing a solution of the reactive bonding agent. In a typical simultaneous application, the intended support for coating is first immersed in an aqueous solution of binding agent and target molecule. Aqueous solvents suitable for use in the present invention include at least about 50% water (by volume), and optionally include between about 10% and about 50% of one or more cosolvents such as isopropyl alcohol. The cosolvent typically has little, if any, effect on the solubility of the binding agent in the solvent system, and on the contrary is used to reduce the surface tension of the solution, in order to promote effective coating of the surface. The coated surface is then exposed to ultraviolet or visible light, in order to promote covalent bond formation between the binding agent, target molecule and material surface, after which the support is washed to remove unbound molecules. In a typical sequential application, the support is first immersed in an aqueous solution of the binding agent and the support coated with the binding agent is then exposed to ultraviolet or visible light, in order to promote formation of covalent bonding on the material surface. After washing to remove any unbound binding agent, a solution containing the target molecule is applied, followed by a second UV illumination resulting in connection of the target molecule to the surface by the binding agent.

When desired, other approaches for surface modification may be employed using the linking agent of the present invention. This approach is particularly useful in situations where a support is difficult to modify using conventional chemistry, or for situations that require durability and exceptional stability of the target molecule on the surface. The present invention provides a useful reagent and method for altering the surface properties of a variety and device of medical, scientific and industrial importance, using a broad spectrum of convenient target molecules. The invention will also be described with reference to the following non-limiting examples. It will be apparent to those skilled in the art that many changes can be made in the described embodiments without departing from the scope of the present invention. In this way, the scope of the present invention should not be limited to the modalities described in this application, but only by the modalities described by the language of the claims and the equivalents of those modalities. Unless otherwise indicated, all percentages are given by weight.

EXAMPLES Example 1 Preparation of 4-Bromomethylbenzophenone (Compound I) 4-Methylbenzophenone, 750 g (3.82 mol), is added to a 5 liter capacity Morton flask, equipped with an overhead stirrer and dissolved in 2850 ml of benzene. The solution is then heated to reflux, followed by dropping 610 g (3.82 moles) of bromine in 330 ml of benzene. The rate of addition was approximately 1.5 ml / min and the flask was illuminated with a 90 watt halogen projecting lamp (90 joules / sec) to initiate the reaction. A timer is used with the lamp to provide a 10% duty cycle (5 seconds on, 40 seconds off), followed in one hour by a 20% duty cycle (10 seconds on, 40 seconds off). At the end of the admission, the product is analyzed by gas chromatography and found to contain 71% of the desired 4-bromomethylbenzophenone, 8% of the dibromo product, and 20% of unreacted 4-methylbenzophenone. After cooling, the reaction mixture is washed with 10 g of sodium bisulfite in 100 ml of water, followed by washing with 3 x 200 ml of water. The product is dried over sodium sulfate and recrystallized twice from toluene: hexane 1: 3. After drying under vacuum, 635 g of 4-bromomethylbenzophenone are isolated, giving a yield of 60%, which has a melting point of 112-114 ° C. The nuclear magnetic resonance ("NMR") analysis (-H NMR (CDC13)) was consistent with the desired product: aromatic protons 7.20-7.80 (m, 9H) and methylated protons 4.48 (s, 2H). All chemical shift values are given in ppm downfield of an internal standard of tetramethylsilane. Example 2 Preparation of Ethylenebis (4-benzoylbenzyldimethylammonium) dibromide (Difoto-Diquat) (Compound II) N, N, N ', N' -etramethylethylenediamine, 6 g (51.7 mmol), are dissolved in 225 ml of chloroform with stirring. 4-Bromomethylbenzophenone, 29.15 g (106.0 mmol), are added as a solid and the reaction mixture is stirred at room temperature for 72 hours. After this time, the resulting solid is isolated by filtration and the white solid is rinsed with cold chloroform. The residual solvent is removed in vacuo and 34.4 g of solid are isolated for a yield of 99.7%, mp 218220 ° C. The analysis in an NMR spectrometer was consistent with the desired product: lH NMR (DMSO d6) aromatic protons 7.20 7.80 (m, 18H), benzylic methylenes 4.80 (br. S, 4H), amine methylenes 4.15 (br. S, 4H ), and methyls 3.15 (br. s, 12H).

Example 3 Preparation of Hexamethylenebis (4-benzoylbenzyl dimethyl ammonium dibromide (Difoto Dicuat) (Compound III) N, N, N ', N'-tetramethyl-1,6-hexanediamine, 1 g (5.80 mmol), is dissolved in 50 ml of chloroform. 4-Bromomethylbenzophenone, 3.35 g (12.18 mmol), then added as a solid and the resulting solution is stirred at 50 ° C for 18 hours, after which time the clear solution is treated with ether. cool to room temperature and then allow the solid to settle The liquid is decanted and the remaining solid is triturated thoroughly with ether The resulting solid is dried under vacuum to give 4.19 g of solid for a quantitative yield, melting point 208- 209 ° C. The analysis in an NMR spectrometer was consistent with the desired product: ** H NMR (DMSO d6) aromatic protons 7.25-7.90 (m, 18H), benzylic methylenes 4.65 (br. S, 4H), methylenes amine 3.25 (br.s, 4H), methyls 3.00 (br.s, 12H) and methylenes 1 .60-2.10 (m, 4H) and 1.20 1.60 (m, 4H). EXAMPLE 4 Preparation of 1,4-Bis (4-benzoylbenzyl) -1,4-dimethylpiperazindinium (Difoto Dicuat) 1,4-dimethylpiperazine dibromide, 1 g (8.76 mmol), is dissolved in 10 ml of chloroform, followed by addition 4.94 g (17.96 mmoles) of 4-bromomethylbenzophenone. The 3 * 'solid dissolved in 15 minutes with precipitation of solid product that occurs after 30 minutes. The mixture is allowed to stir overnight at room temperature under an argon atmosphere. The product is diluted with ether and the solid is filtered and rinsed with ether. The resulting product is dried under vacuum to give 5.82 g of solid to give a quantitative yieldMp 241244 C, a NMR spectrometer analysis was consistent with the desired product: 1H NMR (DMSO d6) aromatic protons 7.25-7.90 (m, 18H), benzylic methylenes 4.80 5.30 (m, 4H), methylenes ring 2.90-4.40 (m, 8H), and methyl 3.25 (br.s, 6H). Example 5 Preparation of dibromide Bis (4-benzoylbenzyl) hexametilentetraminadinio (Difoto Diquat) (Compound V) Hexamethylenetetramine, 1 g (7.13 mmol), and 4-bromomethylbenzophenone, 4.02 g (14.6 mmol) were dissolved in 100 ml of chloroform room temperature. This solution is then heated to reflux for 48 hours. After cooling to room temperature, the product is precipitated by the addition of 1 liter of ether and the resulting oily solid is extracted three times with hot ether. Residual oil is removed under vacuum to give 2.69 g of a white solid for a yield of 54.7%, mp 138-141 ° C. The analysis in an RNM spectrometer was consistent with the desired product: XU NMR (DMS-d6) aromatic protons 7.40-7.90 (m, 18H), benzylic methylenes 5.10 (s, 4H), and ring methylenes 5.00 (br. S, 2H), 4.50 (br.s, 8H) and 4.15 (br.s, 2H). For further purification, a 200 mg sample is loaded onto a normal phase flash silica gel column and the non-polar components are eluted from the column using 10% (v / v) methanol in chloroform. The silica gel bed is then removed and completely extracted with 10% (v / v) methanol in chloroform to give a purified sample. Example 6 Preparation of BiSL tribromide "2- (4 benzoilbenzildimetilamonioetil) -4-benzoilbenzilmetilamonio etill (Trifoto Tricuat) (Compound VI) N, N, N ', N', N '' -pentametildietilentriamina, 1 g (5.77 mmol), dissolved in 20 ml of chloroform with stirring. 4-Bromomethylbenzophenone, 4.84 g (17.60 mmol), is added as a solid and the resulting solution is stirred at 50 ° C for 48 hours. After cooling, the solution is treated with ether and the resulting solid is allowed to settle. The liquid is decanted and the remaining solid is triturated with ether. The resulting oily solid is dried under vacuum for two hours. The resulting solid weighs 5.08 g for a yield of 88.1%, mp 123-128 ° C.

»-AidU Analysis in an RNM spectrometer was consistent with the desired product: XH NMR (CDC13) aromatic protons 7.20-8.10 (m, 27H), benzylic methylenes 5.15 (s, 6H), methylenes 4.05 (br. S, 8H), and methyls 3.35 (br.s, 15H). Example 7 Preparation of Bromide of 4.4-Bis (4-benzoylbenzyl) morpholino (Difoto Monocuat) (Compound VII) Morpholine, 0.85 g (9.76 mmol), is dissolved in ml of dry tetrahydrofuran ("THF"), followed by the addition of 0.39 g (9.76 mmoles) of NaH (60% suspension in oil). The mixture is heated to 50-60 ° C for 10 minutes to form the anion, followed by the addition of 2.68 g. (9.76 mmoles) of 4-bromomethylbenzophenone. The mixture is allowed to stir overnight and then filtered to remove the insolubles, washing the filter cake with 3 x 10 ml of CHC13. The solvents are removed under reduced pressure and the product redissolved in 50 ml of CHC13, followed by washing with 2 x 30 ml of water. After drying over Na2SO4, solvent evaporation gave 2.9 g of product, > 95% pure by gas chromatographic analysis ("GC"). Analysis on an NMR spectrometer was consistent with the desired product: ** H NMR (CDC13) aromatic protons 7.20-7.80 (m, 9H), methylenes adjacent to oxygen 3.55-3.80 (m, 4H), benzylic methylene 3.50 (s, 2H), and methylenes adjacent to nitrogen 2.30 2.55 (m, 4H).

The above product, 2.4 g (8.07 mmol), is dissolved in 5 ml of CHC13 with stirring. 4- Bromomethylbenzophenone, 2.22 g (8.07 mmol), is added together with 120 mg (0.80 mmol) of Nal and the mixture is stirred overnight at room temperature. The mixture is filtered and the solid is washed with 3 x 5 ml of CHC13 to give 0. 95 g of a white solid. The filtrate contains significant amounts of less pure material due to the solubility of the product in organic solvent. ** H NMR (DMSO d6) aromatic protons 7.30-7.85 (m, 18H), benzylic methylenes 4.95 (s, 4H), methylenes adjacent to oxygen 3.90 4. 25 (m, 4H), and methylenes adjacent to nitrogen 3.15-3.60 (m, 4H). Example 8 Preparation of Etilenbis Tetrabromide T (2- (4-benzoylbenzyldimethylammonium) ethyl) -4-benzoylbenzylmethylammoniol (Tetrafoto-Tetracuat) (Compound VIII) 1, 1, 4, 7, 10, 10-hexamethyltriethylenetetramine, 1.0 g (4.34 mmol) ), dissolve in 20 ml of chloroform with stirring. 4-Bromomethylbenzophenone, 5.02 g (18.23 mmol), is added as a solid and the mixture is stirred at 50 ° C for 48 hours. After cooling, the mixture is treated with ether and the resulting solid is isolated by filtration. The product is rinsed with ether and dried under vacuum.

Example 9 Preparation of 1, 1, 4, 4-Tetrakis (4-Benzoylbenzyl) piperazindyinium (Tetrafoto-Diquat) Dibromide (Compound IX) Piperazine, 1 g (11.61 mmol), is dissolved in 20 ml of dry THF, followed by the addition of 0.929 g (23.22 mmoles) of NaH (60% suspension in oil). The mixture is heated at 50-60 ° C for 10-20 minutes to form the anion, followed by the addition of 3.39 g (23.22 mmoles) of 4-bromomethylbenzophenone. The mixture is stirred overnight and filtered to remove insolubles. After evaporation under reduced pressure, the product is redissolved in 50 ml of CHC13 and washed with 2 x 30 ml of water. The product is dried over Na2SO4 and isolated by filtration and evaporation. The above product is then dissolved in 10 ml of CHCl3, followed by the addition of 6.39 g (23.22 mmol) of 4-bromomethylbenzophenone. Nal, 120 mg (0.80 mmol), is added as a catalyst and the mixture is stirred until the starting materials are consumed. The product is isolated by precipitation with ether and the resulting solid is rinsed with ether and dried in vacuo.

Example 10 Prepion of Sodium Salt of N.N Bisr 2 - (4-benzoylbenzyloxy) ethyl -2-aminoethanesulfonic acid). (Difoto-Monosulfate) (Compound X) Diethanolamine, 5.43 g (51.7 mmol), is diluted with 60 ml of CH2C12, followed by the addition of 5.20 g (51.5 mmolee) of triethylamine and 11.3 g (51.7 mmol) of di-t -butyl dicarbonate at room temperature. After complete reaction as indicated by GC analysis, the volatiles are removed under reduced pressure and the residue is dissolved in 45 ml of CHC13. The organic part is extracted successively with 2 x 45 ml of 1 N NaOH, 45 ml of 0.1 N NaOH, and 45 ml of 0.01 N NaOH. Each aqueous extract is then extracted again with 3 x 45 ml of CHC13. The combined organic extracts were purified on a flash chromatography column of silica gel using ethyl acetate to give 6.74 g of protected amine t-BOC as a viscous oil, 63% yield. The analysis on an NMR spectrometer was consistent with the desired product: "H NMR (CDC13) hydroxyl protons and methylenes adjacent to oxygen 3.50-3.90 (m, 6H), methylenes adjacent to nitrogen 3.25 3.50 (m, 4H), and t- butyl protons 1.45 (s, 9H) The amine protected with t-BOC, 6.7 g (32.6 mmol), is diluted with 50 ml dry THF, followed by the addition of 19.72 g (71.72 mmol) of 4-bromomethylbenzophenone, 83 mg (0.55 mmol) of sodium iodide, and 1.75 g (5.43 mmol) of tetra-n-butylammonium bromide 3.1 g (71.7 mmol) of sodium iodide (55% suspension in oil) are then added in portions until approximately 80% of the amount has been added The mixture is allowed to stir at room temperature overnight, followed by the addition of the remaining 20% of the sodium hydride After an additional hour of reaction, the product is diluted with 200 ml of water and the product is extruded with 3 x 100 ml of CHC 13. The bis-benzophenone compound t-BOC is purified in a column of flash chromatography on silica gel, using 95/5 (v / v) CHCl3 / acetonitrile, resulting in 15.60 g (81% theory). Analysis on an NMR spectrometer was consistent with the desired product: XH NMR (CDC13) aromatic protons 7.10-7.80 (m, 18H), benzylic methylenes 4.55 (s, 4H), remaining methylenes 3.30-3.75 (m, 8H), and t-butyl protons 1.45 (s, 9H). The bis-benzophenone compound t-BOC, 0.52 g (0.877 mmol), is dissolved in 5 ml of ethyl acetate plus 2.5 ml of concentrated HCl and the mixture is stirred 30 minutes at room temperature. The pH is then adjusted to approximately 14 by the addition of 10 N NaOH and the desired product is extracted with 4 x 10 ml of CHC13. After drying over sodium sulfate, evaporation of solvent gave the secondary amine product which is used without purification. Analysis on an NMR spectrometer was consistent with the desired product: ** H NMR (CDC13) aromatic protons 7.10-7.80 (m, 18H), benzylic methylenes 4.55 (s, 4H), methylenes adjacent to oxygen 3.60 (t, 4H) , methylenes adjacent to nitrogen 2.85 (t, 4H), and amine proton 2.50 (s, 1H). The secondary amine of the above is diluted with 5 ml of N, N-dimethylformamide, followed by the addition of 0-185 g (0.877 mmol) of sodium salt of 2-bromoethanesulfonic acid. Once the solid dissolves, 0.040 g (1 mmol) of 60% sodium hydride are added and the mixture is heated to 60 ° C. When the reaction is found to proceed slowly, 6.3 mg (0.042 mmol) of sodium iodide is added and heating is continued for 3 days. The product is diluted with 200 ml of water and the product is extracted with 3 x 200 ml of CHC13. The desired sulfonate product is isolated by flash chromatography and silica gel using CHCl3 / CH3OH / NH4OH 90/10/1 (v / v / v) as a solvent to give 150 mg of product for a yield of 27%. Analysis on an NMR spectrometer was consistent with the desired product: E NMR (CDC13) aromatic protons 7.10-7.80 (m, 18H), benzylic methylenes 4.50 (s, 4H), and remaining methylenes 2.90-4.00 (m, 12H).

Example 11 Surface Modification of Polyethylene (PE) by Application of PVP with Compound II A coating solution is prepared by dissolving PVP ("K90F", BASF Corporation) at 20 mg / ml and Compound II at 1 mg / ml in isopropyl alcohol (IPA) / water (1: 1). A rod of high density polyethylene ("HDPE") (length 15 cm (6 inches)) was first rubbed with tissue paper soaked with IPA, after which the rod was pretreated with plasma at 300 mtorr in argon at 250 watts for two minutes. The rod was coated by immersion in the coating solution by immersing it in the solution at 2 cm (0.75 inch) / sec. , receiving for five seconds, and withdrawing at a speed of 0.5 em (0.19 inch) / sec. After removing the rod from the coating solution, it was air dried for 10 minutes. The rod was suspended in half between opposite lamps ELC 4000 (spaced 40 cm (15.7 inches)) containing mercury vapor bulbs of 400 watts that apply 1.5 mW / cm2. from 330 to 340 nm at the illumination distance. The rod is coated and illuminated for three minutes to ensure a uniform setting of the coating. Extensive washing under a flow of deionized water ("DI") and rubbing the surface between the thumb and index finger (approximately 30 seconds) indicates a strongly adherent layer of lubricating PVP as compared to an uncoated rod. The presence of PVP bound on the surface is also verified by staining with a 0.35% solution of Congo Red (Sigma) in DI water. Example 12 Surface Modifi cation of Polyvinyl Chloride (PVC) by Application of PVP with Compound II A PVC urinary catheter (17.8 cm (7.0")) x (outside diameter 4.0 mm (.16")) was coated in Example 11. Again extensive washing in a stream of DI water stream and rubbing the surface with the fingers (approximately 30 seconds) indicates a strongly adherent lubricating coating of PVP, compared to the uncoated control. Also, the presence of PVP bound on the surface is verified by a uniformly stained dark red color, which occurs when dyeing with a 0.35% solution of Congo Red in DI water. Example 13 Superficial Modification of Polyurethane (PU) by Application of PVP with Compound II A polyurethane ("PU") rod (long 15 cm (6")) is coated in the manner described in Example 11, except that the rod it was not pretreated with plasma and it was "HE"??. wet illuminated for 4 minutes (must be dry after lighting). The PU rod was extensively washed in a stream of DI water stream and rubbing the surface with the fingers (approximately 30 seconds) indicates a strongly adherent layer of lubricating PVP. The presence of PVP bound on the surface is verified by staining as described in Example 11. Example 14 Surface Modification of Latex Rubber by Application of PVP with Compound II A latex rubber catheter (16.5 cm (6.5") x 6 mm ( 0.24") outer diameter)) is coated and the presence of the surface-bound coating of PVP is verified in a manner described in Example 13. Example 15 Surface Modification of PE by Applying PVP and Heparin with compound II A piece of HDPE rod ( 15 cm (6") long) is washed and pretreated in a manner described in Example 11. The rod is initially coated using the coating solution and the method described in Example 11. After the initial coating is cured, the rod is subsequently coated by immersion in a solution of PVP (K90F) 20 mg / ml, heparin (Celsus Corp.) at 10 mg / ml, and compound II 1 mg / ml in IPA / water (40:60 v / v) when immersing the solution at 2 cm (0.75") / sec. , residing for 5 seconds, and remove at a speed of 0.5 cm (0.19") / sec The PE stick is suspended halfway between lamps ELC 4000 is turned on and illuminates for 4 minutes, (must be dry after lighting ), as described in Example 11. Rubbing the rod between the index finger and the thumb (approximately 30 seconds) under a water flow DI indicates a lubricating coating of PVP as compared to an uncoated control. Also, the presence of heparin bound on the surface is verified by staining with a 0.1% solution of tolouidine blue O (Sigma) in water GAVE. EXAMPLE 16 Surface Modification of PVC by Application of PVP and Heparin with Compound II A PVC urinary catheter (20 cm (8")) x (outside diameter 4 mm (0.16")) is coated and the presence of both PVP and heparin bound on the surface is checked as described in Example 15. Example 17 Surface Modification of PU by Application of PVP and Heparin with Compound II A PU rod (15 cm (6") long) is coated as described in Example 15, except that plasma pretreatment is not used Evaluation of the rod as described in Example 15 indicates the presence of both PVP and heparin tenaciously bound to the surface of the rod Example 18 Surface Modification of Rubber Latex by Application of PVP and Heparin with compound II A urinary catheter made of latex rubber (15 cm (6") x 6 mm (0.24") outside diameter)) is coated and evaluated as described in Example 15, except that plasma pretreatment was not necessary and the catheter is coated using only a solution of PVP (K90F) at 20 mg / ml, heparin (Celsus Corp.) at 10 mg / ml, and Compound II at 1 mg / ml in IPA / water (40:60 v / v) Evaluation of the latex catheters described in Example 15 indicates the presence of PVP and heparin bound to the surface Example 18 Surface modification of PU by Application of PVP with compound III A coating solution is prepared by dissolving PVP (K90F) at 20 mg / ml, and Compound III at 1 mg / ml in IPA / water (1: 1 v / v) A PU rod (10 cm (3.9") long) is initially rubbed with a tissue soaked with IPA.

The rod is coated by immersion in the coating solution when submerged in the solution at 2 cm (0.75") / sec., Residing for 5 seconds, and removed at a rate of 1 cm (0.39") / sec. The PU rod is removed from the coating solution and suspended halfway between opposite ELC 4000 lamps (40 cm (15.7") spaced) containing 400 watt mercury vapor bulbs, which apply 1.5 mW / cm2. -340 nm, at the illumination distance The wet rod is turned and illuminated for 3 minutes to ensure a uniform setting of the coating The surface of the cured rod is rubbed by hand under a flow of DI water for 15 seconds and then stain with 0.35% Congo Red solution indicating the presence of PVP on the surface, the rod is again rubbed as previously described, followed by another stained with Congo Red, the coated section of the rod is uniformly stained dark red and It feels lubricated compared to the uncoated control There was no indication that the coating had come off A control rod coated with only a 20 mg / ml solution of PVP in IPA / water (1: 1 v / v) was not lubricant after of rubbing, and does not stain with Congo Red, indicating that the PVP was not tenaciously bound to the PU surface. Example 20 Surface modification of PU by application of PVP with compound IV. V or VI Polyurethane rods (10 cm (3.9")) were coated as described in Example 19, except that the coating solutions contain 1 mg / ml of Compounds IV, V or VI The presence of a lubricant coating using Each of the entanglement agents is verified as indicated in Example 19. Example 21 Surface Modification of PE by Application of PVP with Compound III, IV, V or VI HDPE Rods (12 cm (4.7")) are coated as described in Example 19, with the same concentration of PVP and Compound III, IV, V or VI, except that the rods were pretreated with plasma at 300 mtorr in oxygen at 100 watts for 3 minutes. Evaluation of the surface of the rods by both hand rubbing and spotting with Congo Red as described in Example 19, for all four gauze agents indicates a uniformly stained dark red coating, which felt lubricant compared to the controls not coated. Example 22 Superficial Modification of HDPE LDPE, PU and Nylon with PVOI. PVP and compounds II. or VI Two "coating solutions" were prepared as follows: solution # 1 contains PV01 / PVP (K90F) / Compound II (10/20/1 mg / ml, respectively) in 30% (v / v) IPA in water. Solution # 2 contains PVOl / PVP (K90F) / Compound VI (10/20/1 mg / ml, respectively) in 30% (v / v) IPA in water: PV01 (PVP photo) is prepared by copolymerizing l-vinyl -2-pyrrolidone and N- (3-aminopropyl) methacrylamide (APMA), followed by photoderivatization of the polymer using 4-benzoylbenzoyl chloride, under Schotten-Baumann conditions, for example a two-phase organic / aqueous reaction system. All four substrates, PU rods and LDPE pipe (31 cm (12.2")), and HDPE rods and nylon pipe (20 cm (7.87")) were rubbed with tissue soaked with IPA and coated by immersion in each of the coating solutions when submerged in the solution at 2 cm (0.75") / sec., residing for 5 seconds, and removing at a speed of 1 cm (0.19") / sec. The substrates were suspended in half between two opposite lamps ELC 4000, as previously described (Example 11) and the wet substrates were turned on. illuminated for 4 minutes to properly cure the coatings.The cured substrates were rubbed (10 times) between the index finger and the thumb) approximately 30 seconds (in a DI water flow (stained with 0.35% Congo Red solution, rubbed again ( 30 times) and re-staining, to demonstrate the presence of bound PVP The tenacity of the coatings on the substrates is evaluated by the coefficient of friction (COF = coefficient of friction) using a modified ASTM protocol for pipe. the addition of reagents II and VI greatly improves the durability of the coatings with only a slight decrease in lubricity compared to the PVOl / PVP controls. Superficial HDPE LDPE coating. PU and Nylon with PVOI. and compound II. or VI The four different substrates were coated with two different solutions. Solution # 1 contains PVOl / PVP (K90F) / Compound II (20 / 0.5 mg / ml, respectively) in 30% (v / v) IPA in water. Solution # 2 consists of PVOl / Compound VI (20 / 0.5 mg / ml, respectively) in 30% (v / v) IPA in water. The materials were coated and evaluated as described in Example 22. The surface coatings were tougher compared to the PVOl / PVP controls without the ligand or bonding agents but they were also less lubricant than the controls, but well within acceptable ranges .

. * * Axis? Yj 4 Surface Modification of PU by Sequential Application of compound II, III. IV. V or VI and PVP PU rods were rubbed with a tissue soaked with IPA. The rods were coated by immersion in solutions of Compound II (10 mg / ml), Compound III (10 mg / ml), Compound IV (4 mg / ml), Compound V (10 mg / ml) or Compound VI (10 mg / ml) in IPA of water (1: 1 v / v) in the manner described in Example 11. The rods were illuminated for one minute with ELC 4000 lamps as previously described (Example 11) and rotated to ensure a uniform setting of the coating. The rods were then coated by immersion in a PVP solution (20 mg / ml) in IPA, allowed to air dry and then illuminated for three minutes as previously described (Example 11). The cured rods were rubbed between the fingers under running DI water (15 seconds) and then stained with 0. 35% of Congo Red to demonstrate the presence of bound PVP on the surface. All photoreactors produce tough linings and lubricants on the PU rods, except that the coating of Compound IV exhibits a decrease in the toughness and lubricity of the PVP coating.

Example, 25 Superficial Modification of HDPE by Sequential Application of compound II. III. IV. V or VI and PVP Flat pieces of HDPE (5 cm (1.97") x 1.5 cm (0.59") x 4 mm (0.16") were first rubbed with a tissue soaked with IPA, and then each side was pretreated at 300 mtorr in oxygen at 100 watts per minute The pieces were then immersed in solutions of compounds II, III, IV, V or VI at previously reported concentrations (Example 24) The flat pieces were then illuminated for one minute as described in Example 11. After curing, the pieces were coated by immersion in a PVP solution (20 mg / ml) in IPA, air-dried and illuminated for three minutes (see Example 11) Extensive washing under a flow of DI water and rubbing between index and thumb (2 x 15 sec), followed by staining with Congo Red 0.35% indicates tenacious and lubricant coatings with the use of each photoreactive Example 26 Surface modification of PU and PVP and compound VII Two solutions of coating were prepared as follows: Solution # 1 contains PVP (K90F) / Compound VII (17/1 mg / ml, respectively) in 50% (v / v) of IPA in water. Solution # 2 contien @;? f > VP (K90F) (12 mg / ml) in 50% - Ti * (v / v) IPA in water. PU rods (16 cm (6.3")) were rubbed with IPA-harvested tissue and coated by immersion in each of the coating solutions upon immersion in the solution at 2 cm (0.75") / sec. , residing for 30 seconds, and removing at a speed of 0.7 cm (0.27") / sec Samples of both control rods and those coated with compound VII were allowed to air dry for 10 minutes before lighting or illuminated in The substrates were suspended in the middle between two opposite ELC 4000 lamps (40 cm (15.7") opposite) as previously described (Example 11). The rods were turned and illuminated for two minutes (dry lighting) or four minutes (wet lighting). Extensive washing of all rods under a flow of DI water, and rubbing the surface between the index and thumb (approximately 30 seconds) indicates a strongly adherent layer of lubricating PVP, using compound VII compared to controls containing only PVP. Also, the presence of bound PVP on surfaces treated with PVP and compound VII is verified by staining uniformly dark red color produced by staining with a 0.35% solution of Congo Red in DI water. Rods only coated with absorbed PVP do not exhibit color or a very light pink stain. Example 27 Surface Modification of PU with PVP and Compound X A coating solution was prepared by dissolving PVP (K90F) at (20 mg / ml, and Compound X at 1 mg / ml in DI water containing 0.5 equivalent of 0.1 N NaOH. A PU rod (18 cm (7.1"long) is first rubbed with a tissue soaked with IPA, and coated by immersion in the coating solution when immersed in the solution at 2 cm (0.74") / sec, reside for 15 seconds and remove it at a speed of 1 cm (0.38") / sec. the wet PU rod is suspended halfway between opposite ELC 4000 lamps, rotates and illuminates for three minutes as described in the example 11. Extensive washing under a flow of DI water, and rubbing the surface between the index and thumb (approximately 30 seconds) indicates an adherent layer of lubricating PVP as compared to an uncoated rod. The presence of PVP bound on the surface is also verified by a 0.35% solution of Congo Red in DI water.

Claims (26)

1. CLAIMS 1. - A photoactivable chemical bonding agent characterized in that it comprises a bi-functional or higher functional non-polymeric, charged photoactivable compound.
2. 2. - A binding agent according to claim 1, characterized in that the agent comprises two or more photoreactive groups and one or more charged groups, sufficient to allow the agent to be used as an entanglement agent in a solvent system having water as a main component.
3. 3. - A binding agent according to claim 2, characterized in that the charged group is selected from the group consisting of salts of organic acids, onium compounds and protonated amines and combinations thereof.
4. 4. - A binding agent according to claim 3, characterized in that the salts of organic acids are chosen from the group consisting of sulfonate phosphate and carboxylate groups and the onium compounds are selected from the group consisting of quaternary ammonium, sulfonium groups and phosphonium and their combinations.
5. 5. - A binding agent according to claim 2, characterized in that the photoreactive groups are provided by two or more radicals, each containing an aryl ketone.
6. 6. - A binding agent according to claim 5, characterized in that each aryl ketone is selected from the group consisting of acetone phenone, benzophenone, anthrquinone, anthrone and anthrone-type heterocycles and their substituted derivatives.
7. 7. A photoactivable entanglement agent comprising a compound of the formula: XYX wherein each X, independently, is a radical containing a photoreactive group and Y is a radical containing one or more charged groups, wherein the number and The type of the charged group (s) is sufficient to provide the molecule with sufficient aqueous solubility to allow the agent to be used in a solvent system having water as the main component.
8. 8. - An interlacing agent according to claim 7, characterized in that Y comprises one or more charged groups selected from the group consisting of salts of organic acids, onium compound and protonated amines and combinations thereof.
9. 9. - An entanglement agent according to claim 8, characterized in that the salts of organic acids are selected from the group consisting of sulfonate, phosphonate and carboxylate group, and the onium compounds are selected from the group consisting of quaternary ammonium groups, sulfonium and phosphonium and their combinations.
10. 10. - An interlacing agent according to claim 7, characterized in that each X comprises photoreactive groups in the form of an aryl ketone.
11. 11. An entanglement agent according to claim 10, characterized in that each aryl ketone is selected from the group consisting of acetone phenone, benzophenone, anthrquinone, anthrone and anthrone heterocycles and their substituted derivatives.
12. 12. - An interlacing agent according to claim 8, characterized in that Y comprises an onium compound consisting of one or more quaternary ammonium groups.
13. 13. - An entanglement agent according to claim 12, characterized in that the onium compound comprises a linear or heterocyclic radical selected from the group consisting of: R3 3 R3 R3 R ** - N- R'- N R'-N- R'- N -R «- R2 fi2 R2 R2 wherein each R1 independently is a radical containing an alkylene, oxyalkylene, cycloalkylene, arylene or arylkylene group, each R2 independently is a group containing an alkyl, oxy, alkyl, cycloalkyl, aryl or aralkyl group and each R3 independently is already a couple no electron binder, a hydrogen atom or a radical of the. same definition as R2, wherein the groups R1, R2 and R3 may contain substituents or heteroatoms that do not interfere.
14. 14. - A photoactivable entanglement agent selected from the group consisting of: 2Bt "
15. 15. - A method for coating a surface with a target molecule, the method is characterized in that it comprises the steps of providing a photoactivatable chemical bonding agent comprising a bi-functional or higher functional non-polymeric photoactivable compound, charged, forming a solvent system having Water as the main component and comprising the binding agent and a target molecule, providing the solvent system in proximity of binding to the surface, and activating the photoreactive groups of the binding agent in order to interlace the target molecule to the surface.
16. 16. - A method according to claim 15, characterized in that the binding agent comprises two or more photoreactive groups and one or more charged groups.
17. 17. A method according to claim 16, characterized in that the charged group is selected from the group consisting of salts of organic acids, onium compounds and protonated amines and combinations thereof.
18. 18. - A method according to claim 17, characterized in that the salts of organic acids are chosen from the group consisting of sulfonate, phosphonate and carboxylate group and onium compounds are selected from the group consisting of quaternary ammonium, sulfonium and phosphonium groups and your combinations
19. 19. - A method according to claim 16, characterized in that the photoreactive groups are provided by two or more radicals each containing an aryl ketone.
20. 20. A method according to claim 19, characterized in that each aryl ketone is selected from the group consisting of acetophenone, benzophenone, anthraquinone and anthrone-type heterocycles and their substituted derivatives.
21. 21. A surface containing a coating comprising a target molecule intertwined with the surface by activation of a photoactivatable chemical bonding agent, the agent comprising a bi-functional or functional non-polymeric charged top active compound.
22. 22. - A surface according to claim 21, characterized in that the binding agent provides two or more photoactivatable groups and one or more charged groups sufficient to allow the agent to be used as an entanglement agent in a solvent system having water as a main component.
23. 23. - A surface according to claim 22, characterized in that the charged group is selected from the group consisting of salts of organic acids, onium compounds and protonated amines and combinations thereof.
24. 24. A surface according to claim 21, characterized in that the salts of organic acids are chosen from the group consisting of sulfonate, phosphonate and carboxylate groups, and the onium compounds are selected from the group consisting of quaternary ammonium, sulfonium groups and phosphonium and their combinations.
25. 25. A surface according to claim 24, characterized in that the photoreactive groups are provided by two or more radicals each containing an aryl ketone.
26. 26. A surface according to claim 25, characterized in that each aryl ketone is selected from the group consisting of acetophenone, benzophenone, anthraquinone, anthrone and anthrone heterocycles and their substituted derivatives.