CN107857876A - One kind enhancing fluorescence probe and preparation method thereof - Google Patents
One kind enhancing fluorescence probe and preparation method thereof Download PDFInfo
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- CN107857876A CN107857876A CN201711210236.8A CN201711210236A CN107857876A CN 107857876 A CN107857876 A CN 107857876A CN 201711210236 A CN201711210236 A CN 201711210236A CN 107857876 A CN107857876 A CN 107857876A
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- 239000000523 sample Substances 0.000 title claims abstract description 48
- 230000002708 enhancing effect Effects 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000000126 substance Substances 0.000 claims abstract description 11
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 238000006467 substitution reaction Methods 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract description 18
- 238000001514 detection method Methods 0.000 abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 229920001223 polyethylene glycol Polymers 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 0 CCc(cc1C2=O)ccc1-c1c(cc(cc3)I*)c3c(C3C=CC(CBr)=CC33)c4c1c2ccc4C3=O Chemical compound CCc(cc1C2=O)ccc1-c1c(cc(cc3)I*)c3c(C3C=CC(CBr)=CC33)c4c1c2ccc4C3=O 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000005283 ground state Effects 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- -1 methoxyl group Chemical group 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000005375 photometry Methods 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 206010008428 Chemical poisoning Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910001914 chlorine tetroxide Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229910000437 dibromine pentoxide Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000000695 excitation spectrum Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000000013 phosphorescence detection Methods 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 229930187593 rose bengal Natural products 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
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- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/334—Polymers modified by chemical after-treatment with organic compounds containing sulfur
- C08G65/3344—Polymers modified by chemical after-treatment with organic compounds containing sulfur containing oxygen in addition to sulfur
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
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- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
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- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N21/643—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" non-biological material
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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Abstract
The present invention relates to one kind enhancing fluorescence probe and preparation method thereof, its chemical structure of general formula is as follows：In formula, R1And R2The alkyl that carbon number is 1~6 is independently selected from, Z is PEG the or PEG derivatives groups that molecular weight is 500~10000.Fluorescence probe intermediate is caused to connect upper two fluorophors by using special MOLECULE DESIGN, and PEG or PEG derivatives are used on the fluorescence probe intermediate, the water solubility of fluorescence probe can be so greatly enhanced, fluorescence intensity is strengthened at double, so as to improve its Detection results to specific molecular (such as singlet oxygen).
Description
Technical field
The invention belongs to fluorescence probe field, is related to a kind of enhancing fluorescence probe and preparation method thereof, single available for detection
Line state oxygen.
Background technology
Singlet oxygen, the oxygen of the stable ground state oxygen molecule from generally breathing is different, is that one kind is in reactive oxygen species
Existence form.Compared with ground state, the chemical property of singlet oxygen is more active, more unstable, and oxidisability is very strong, can cause each
The oxidation of kind material.Singlet oxygen can participate in a variety of body biochemical reactions and physiology course, for example, signal transduction, enzyme reaction,
Cell division, tissue peroxidating, inflammation, aging, Phagocytosis, tumour and chemical poisoning, the double of Various Complex are produced to body
Recast is used.On the one hand, singlet oxygen has stronger toxicity, can cause the damage of body, triggers aging and various diseases；It is and another
On the one hand, it is the major antibacterial agent of organism immune system again, it may also be used for the photodynamic therapy of cancer.
At present, a small amount of singlet oxygen is quantitatively detected in the aqueous solution in physiological conditions to have difficulties, essentially consist in its longevity
Order that short, reactivity is high.The method of existing singlet oxygen detection is broadly divided into (such as the paramagnetic resonance skill of detection method in gas phase
Art, emission spectrum, photo-ionisation technology and calorimetry etc.) and liquid phase in detection method (such as phosphorescence detection method, Chemical Trapping inhale
Light photometry, chemoluminescence method, fluorescence detection etc.).Above-mentioned detection method or cost are high-leveled and difficult with application, or because singlet
Oxyluminescence efficiency is low and causes sensitivity low, and detecting signal is weak.
The Chinese invention patent of Application No. 201610093502.2 discloses a kind of dyestuff for being used to detect singlet oxygen
With fluorescence probe and preparation method thereof, it is fluorescence probe corresponding to Material synthesis by using bridged piperazine derivatives, and be fabricated to inspection
Test agent box.Obtained fluorescence probe in this application, has high sensitivity and selectivity to singlet oxygen, greatly expands such
The application of fluorescence probe, such as available for the singlet oxygen detection in environment, chemical food and biologic medical field；But
It is that the fluorescence intensity of the fluorescence probe still has the space of lifting.
The content of the invention
A kind of enhancing fluorescence probe is provided the invention aims to overcome the deficiencies in the prior art.
To reach above-mentioned purpose, the technical solution adopted by the present invention is：One kind enhancing fluorescence probe, its chemical constitution are led to
Formula is as follows：
In formula, R1And R2The alkyl that carbon number is 1~6 is independently selected from, Z is that molecular weight is 500~10000
PEG or PEG derivatives groups.
Optimally, R1And R2It is ethyl.
Optimally, Z isR is O, S or NH.
A further object of the present invention is to provide a kind of preparation method of above-mentioned enhancing fluorescence probe, and it includes following step
Suddenly：
Added into reaction vessel
Substitution reaction is carried out at 40~80 DEG C；Mole
The ratio between amount is 1:2~2.2.
Optimally, it is describedPreparation method comprise the following steps：(a1) willCarry out the substitution reaction of Br free radicals and generate the first product(a2) first production is made
Thing carries out substitution reaction with chlorosulfonic acid, generates the second product(a3) by second product with
PEG or PEG derivatives carry out substitution reaction.
Because above-mentioned technical proposal is used, the present invention has following advantages compared with prior art：Present invention enhancing fluorescence
Probe, make it that fluorescence probe intermediate connects upper two fluorophors by using special MOLECULE DESIGN, and the fluorescence probe
PEG or PEG derivatives are used on intermediate, can so be greatly enhanced the water solubility of fluorescence probe, fluorescence intensity is able into
Strengthen again, so as to improve its Detection results to specific molecular (such as singlet oxygen).
Brief description of the drawings
Accompanying drawing 1 is the synthetic line figure for strengthening fluorescence probe in embodiment 1；
Accompanying drawing 2 is before and after the enhancing fluorescence probe synthesized in the embodiment of the present invention 1 reacts in room temperature DMF with singlet oxygen
Fluorescent emission collection of illustrative plates contrast (λ ex=400nm), wherein1O2Produced within 15 minutes by quick dose of phot-luminescence (rose-red)；
Accompanying drawing 3 is before and after the enhancing fluorescence probe synthesized in the embodiment of the present invention 1 reacts in room temperature water with singlet oxygen
Fluorescent emission collection of illustrative plates contrast (λ ex=400nm), wherein1O2Produced within 15 minutes by quick dose of phot-luminescence (rose-red).
Embodiment
Present invention enhancing fluorescence probe, its chemical structure of general formula are as follows：
In formula, R1And R2The alkyl that carbon number is 1~6 is independently selected from, Z is that molecular weight is 500~10000
PEG or PEG derivatives groups.Fluorescence probe intermediate is caused to connect upper two fluorescent bases by using special MOLECULE DESIGN
Group, and PEG or PEG derivatives are used on the fluorescence probe intermediate, the water solubility of fluorescence probe can be so greatly enhanced,
Fluorescence intensity is strengthened at double, so as to improve its Detection results to specific molecular (such as singlet oxygen).
R1And R2Both preferably ethyl.Z be preferably methoxyl group modification PEG or PEG derivatives, R O, S or NH.Above-mentioned increasing
The chemical structure of general formula of hyperfluorescence probe is optimal to be
N size is according to specific molecular weight
It is determined that.
The preparation method of above-mentioned enhancing fluorescence probe, it comprises the following steps：
Added into reaction vessel
Substitution reaction is carried out at 40~80 DEG C；Mole
The ratio between amount is 1:2~2.2.
It is and describedPreparation method comprise the following steps：(a1) willEnter
The substitution reaction of row Br free radicals generates the first product(a2) first product is made to be taken with chlorosulfonic acid
Generation reaction, generates the second product(a3) second product is entered with PEG or PEG derivatives
Row substitution reaction.AndThen byIt is anti-with piperazine
It should be made.
The present invention is further described below in conjunction with accompanying drawing embodiment.
Embodiment 1
The present embodiment provides a kind of enhancing fluorescence probe and preparation method thereof, and the chemical structural formula of the enhancing fluorescence probe is such as
Under：Its preparation method is as follows, comprises the following steps
(as shown in Figure 1)：
(a1) in 50mL there-necked flasks, and addition HOCD (1g, 2.43mmol, 1eq, i.e.,), carbon tetrachloride
(10mL), NBS (0.95g, 5.36mol, 2.2eq, i.e. N-bromosuccinimide), benzoyl peroxide (5.88mg,
0.0243mmol, 0.01eq), it is heated to reflux 19 hours under nitrogen protection, is cooled to 0 DEG C, filtering, filter cake is washed with carbon tetrachloride
Wash, concentrate, then by column chromatography, obtain compound 1.24g (90%) blue solid (first product).Survey
Hydrogen modal data be：1H NMR(300MHz,CDCl3)δ(ppm):8.81 (s, 2H), 8.75 (d, J=6.0Hz, 2H), 8.28
(s, 2H), 8.25 (d, J=6.0Hz, 2H), 7.59-7.56 (m, 4H), the carbon modal data that 2.57 (s, 4H) are measured are：13C NMR
(75MHz,CDCl3)d(ppm):1884.73,141.09,136.67,134.96,134.06,132.62,131.58,130.21,
129.10,128.66,128.71,126.38,124.29,26.45.HREI-MS m/z calcd:C30H18Br2O2([M]+)；
567.9674,found:567.9665；
(a2) in 50mL single port bottles, the first product (800mg, 1.38mmol, 1eq) is added, adds chlorosulfonic acid (16mL),
It is heated to reflux 24 hours, reaction solution is added in 20mL frozen water, extracted with dichloromethane, concentrated post purifies to obtain compound 2
652mg (71%) blue solid (second product)。1H NMR(300MHz,CDCl3)δ(ppm):
9.25 (d, J=3.0Hz, 1H), 8.75 (d, J=9.0Hz, 1H), 8.58-6.53 (m, 2H) 8.15 (s, 2H), 7.98-7.89
(m,3H),7.59-7.52(m,2H),2.53(s,2H),2.51(s,2H).13C NMR(75MHz,CDCl3)δ(ppm):
182.94,182.91,142.05,140.67,140.15,134.57,134.14,132.93,132.58,131.40,131.34,
130.80,130.70,130.63,130.00,129.78,129.64,129.54,129.39,129.26,129.17,128.88,
128.39,128.09,126.22,125.36,121.68,21.45ppm.HRESI-MS:m/z cacld.C30H17Br2ClO4S:
665.8903(M+),found:665.8895(weak peak).Cacld:C30H18Br2O5S[M-H]-646.9242
(sulfonate),found:647.9235(strong peak)；
(a3) in 50mL single port bottles, the second product (200mg, 0.3mmol, 1eq) is added, adds dichloromethane (5mL),
Et3N (triethylamine, 37mg, 0.36mmol, 1.2eq), methoxy poly (ethylene glycol) (i.e. mPEG-OH, MW=1000) (23mg,
0.36mmol, 1.2eq), react 5 hours at 50 DEG C, be cooled to room temperature, water 1mL on the rocks, concentration, cross post and purify to obtain tertiary industry
Thing 144mg is (i.e.68%) blue solid1H NMR(300MHz,CDCl3)δ
(ppm):9.27(m,1H),8.79(m,1H),8.68-6.57(m,2H)8.25(m,2H),7.98-7.89(m,3H),7.59-
7.52(m,2H),4.25-4.20(m,2H),3.63-3.60(m,3H),3.45-3.42(m,2H),2.53(m,2H),2.51(m,
2H)；
(b1) take piperazine (5.31mg, 0.062mmol) to be dissolved in dry methylene chloride (DCM) (6mL), then add benzo
Triazole-N, N, N', N'-15 tetramethylurea hexafluorophosphate (HBTU) (34.3mg, 0.091mmol), N, N- diisopropyl second
After base amine (DIPEA) (31 μ L, 0.184mmol), withIn room
It is stirred overnight, produces under temperatureCrude product.Product is purified：Respectively with HCl (1M,
10mL) and NaHCO3The aqueous solution (2 times, each 10mL) washing reaction mixture；Collect organic phase and rotary evaporated to dryness is dry.It is logical
Cross silica gel column chromatography (eluent：CH2Cl2/ MeOH, 20v/v=97：3) purification of crude product, pure violet compound is obtained
(27.4mg, 89%).1H NMR (300MHz, CDCl3) δ=8.76 (d, J=9Hz, 1H), 8.68 (d, J=9Hz, 1H), 8.31
(d, J=6Hz, 2H), 7.57-7.49 (m, 5H), 7.40-7.35 (m, 3H), 7.11 (d, J=6Hz, 1H), 3.94 (d, J=
12H, 1H), 3.26 (d, J=12H, 1H), 2.98-2.67 (m, 5H), 2.56 (s, 3H), 2.50 (s, 3H), 2.32 (t, J=
12H, 1H)；13C NMR (126MHz, CDCl3) δ=184.72,168.67,139.35,138.39,138.26,135.00,
134.34,133.66,133.62,133.56,132.15,130.75,129.65,129.21,128.82,128.23,128.14,
127.59,127.14,126.66,126.14,126.06,125.79,5 125.64,47.96,45.39,41.28,21.55,
21.37.C34H29N2O2[M]+HRESI-MS Cacld:497.2224；found:497.2225.
(c) in 50mL single port bottles, third product (100mg, 0.141mmol, 1eq), CH are added3CN(5mL),K2CO3
(98mg, 0.705mmol, 5.0eq) and70℃
Lower reaction 8 hours, is cooled to room temperature, concentrates, and fluorescence probe 150mg (68%) light red solid must be strengthened by crossing post and purifying.1H
NMR (300MHz, CDCl3) δ=9.08 (s, 1H), 8.79-8.73 (m, 6H), 8.23 (s, 4H), 8.17 (m, 3H), 8.04 (m,
6H), 7.78 (d, 3H), 7.62 (s, 4H), 7.45 (m, 3H), 6.92 (m, 3H), 4.25-4.20 (m, 2H), 3.63-3.60 (m,
3H), 3.45-3.42 (m, 28H), 3.26-3.14 (m, 10H), 2.54m, 6H), 2.53 (m, 6H), 1.25 (m, 12H).
Embodiment 2
The present embodiment provides a kind of enhancing fluorescence probe and preparation method thereof, the chemical structural formula of the enhancing fluorescence probe and
Reactions steps with basically identical in embodiment 1, unlike：(a3) the mPEG-OH molecular weight used in is 10000, step
(b1) raw material used in is
Embodiment 3
The present embodiment provides a kind of enhancing fluorescence probe and preparation method thereof, the chemical structural formula of the enhancing fluorescence probe and
Reactions steps with basically identical in embodiment 1, unlike：(a3) the mPEG-OH molecular weight used in is 500.
3 parts of photosensitizer rose bengals (2 μ L, 0.5mg/mL, be dissolved in 10mM PBSs, pH=7.4) stock solution is taken, respectively
The probe mixing added in embodiment 1 to embodiment 3；By solution several minutes under the light of fiber luminaire, and with glimmering
Photometry records fluorescence intensity change.Wherein, shown in experimental result Fig. 2 in embodiment 1, enhancing fluorescence probe DMF (1 μM) with
Fluorescence excitation spectral intensity enhances 148 times respectively after singlet oxygen reaction；And obtained enhancing is glimmering in embodiment 2 and embodiment 3
Fluorescence excitation spectral intensity enhances 146 times to light probe respectively, 145 times (with application number after DMF (1 μM) and singlet oxygen reaction
For the IIIa probes in 201610093502.2 Chinese invention patents as a comparison case, measure and add 60 times), it is clear that they are big
It is higher than comparative example greatly.In the PBS of simulation biological physiology environment, concentration is 0.1 μM of probe and single line in comparative example 1
Fluorescence excitation spectrum distinguishes intensity 120 times (as shown in Figure 3) after the reaction of state oxygen；And obtained enhancing in embodiment 2 and embodiment 3
Fluorescence excitation spectral intensity enhances 116 times, 115 times respectively after fluorescence probe reacts in PBS with singlet oxygen, about
80% measured in organic solvent DMF, this illustrate the probe it is water-soluble not than oil-soluble reduce how much, have good
It is water-soluble.
The above embodiments merely illustrate the technical concept and features of the present invention, and its object is to allow person skilled in the art
Scholar can understand present disclosure and implement according to this, and it is not intended to limit the scope of the present invention, all according to the present invention
The equivalent change or modification that Spirit Essence is made, it should all be included within the scope of the present invention.
Claims (5)
1. one kind enhancing fluorescence probe, it is characterised in that its chemical structure of general formula is as follows：
In formula, R1And R2Be independently selected from carbon number be 1~6 alkyl, Z be the PEG that molecular weight is 500~10000 or
PEG derivatives groups.
2. enhancing fluorescence probe according to claim 1, it is characterised in that：R1And R2It is ethyl.
3. enhancing fluorescence probe according to claim 1, it is characterised in that：Z isR is O, S
Or NH.
4. the preparation method of any enhancing fluorescence probe in claims 1 to 3, it is characterised in that it comprises the following steps：
Added into reaction vesselCH3CN、K2CO3With
40~80 DEG C of progress substitution reactions；Mole
The ratio between be 1:2~2.2.
5. strengthen the preparation method of fluorescence probe according to claim 4, it is characterised in that：It is described
Preparation method comprise the following steps：
(a1) willCarry out the substitution reaction of Br free radicals and generate the first product
(a2) first product is carried out substitution reaction with chlorosulfonic acid, generate the second product
(a3) second product and PEG or PEG derivatives are subjected to substitution reaction.
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| CN102300861A (en) * | 2009-02-03 | 2011-12-28 | 百奥提姆股份有限公司 | Xanthene dyes comprising a sulfonamide group |
| WO2012039685A1 (en) * | 2010-09-24 | 2012-03-29 | Agency For Science, Technology And Research | A nanoprobe comprising gold colloid nanoparticles for multimodality optical imaging of cancer and targeted drug delivery for cancer |
| CN107099165A (en) * | 2016-02-19 | 2017-08-29 | 苏州工业园区新国大研究院 | Dyestuff and fluorescence probe for detecting singlet oxygen and preparation method thereof |
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| CN102300861A (en) * | 2009-02-03 | 2011-12-28 | 百奥提姆股份有限公司 | Xanthene dyes comprising a sulfonamide group |
| WO2012039685A1 (en) * | 2010-09-24 | 2012-03-29 | Agency For Science, Technology And Research | A nanoprobe comprising gold colloid nanoparticles for multimodality optical imaging of cancer and targeted drug delivery for cancer |
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| CN110256644A (en) * | 2019-05-20 | 2019-09-20 | 徐从燕 | It is a kind of for detecting the fluorescence probe and preparation method thereof of heavy metals in industrial wastewater ion |
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