CN114773343A - Copper and zinc ion dual-detection fluorescent probe and preparation method thereof - Google Patents
Copper and zinc ion dual-detection fluorescent probe and preparation method thereof Download PDFInfo
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- 239000007850 fluorescent dye Substances 0.000 title claims abstract description 65
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 238000001514 detection method Methods 0.000 title claims abstract description 28
- 239000010949 copper Substances 0.000 title claims abstract description 19
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 229910052802 copper Inorganic materials 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title abstract description 11
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims abstract description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 47
- 229910001431 copper ion Inorganic materials 0.000 claims abstract description 39
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 claims abstract description 20
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 20
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims abstract description 16
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011159 matrix material Substances 0.000 claims abstract description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 3
- 238000006482 condensation reaction Methods 0.000 claims abstract description 3
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- 238000006243 chemical reaction Methods 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
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- 238000010992 reflux Methods 0.000 claims description 6
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- 239000012295 chemical reaction liquid Substances 0.000 claims description 3
- DDXLVDQZPFLQMZ-UHFFFAOYSA-M dodecyl(trimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)C DDXLVDQZPFLQMZ-UHFFFAOYSA-M 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims 1
- 239000011701 zinc Substances 0.000 abstract description 15
- 230000004044 response Effects 0.000 abstract description 6
- 230000035945 sensitivity Effects 0.000 abstract description 4
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- 239000000243 solution Substances 0.000 description 19
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- 229910021645 metal ion Inorganic materials 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 16
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- -1 hydrazone compound Chemical class 0.000 description 7
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- 229910052725 zinc Inorganic materials 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
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- 241000894007 species Species 0.000 description 2
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- JDQLUASCFQVIBB-UHFFFAOYSA-N (8-methyl-9-naphthalen-1-ylpurin-6-yl)hydrazine Chemical compound N(N)C1=C2N=C(N(C2=NC=N1)C1=CC=CC2=CC=CC=C12)C JDQLUASCFQVIBB-UHFFFAOYSA-N 0.000 description 1
- FSMYWBQIMDSGQP-UHFFFAOYSA-N 4-oxochromene-3-carbaldehyde Chemical compound C1=CC=C2C(=O)C(C=O)=COC2=C1 FSMYWBQIMDSGQP-UHFFFAOYSA-N 0.000 description 1
- XYGYJJDBKUZUOR-UHFFFAOYSA-N 6-chloro-4-N-naphthalen-1-ylpyrimidine-4,5-diamine Chemical compound NC1=C(Cl)N=CN=C1NC1=CC=CC2=CC=CC=C12 XYGYJJDBKUZUOR-UHFFFAOYSA-N 0.000 description 1
- IQWVQIJEWNNHSJ-UHFFFAOYSA-N 6-chloro-8-methyl-9-naphthalen-1-ylpurine Chemical compound ClC1=C2N=C(N(C2=NC=N1)C1=CC=CC2=CC=CC=C12)C IQWVQIJEWNNHSJ-UHFFFAOYSA-N 0.000 description 1
- 208000029011 Copper metabolism disease Diseases 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 208000019637 Infantile Diarrhea Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
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- 229910021641 deionized water Inorganic materials 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
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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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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- 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
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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Abstract
The invention discloses a dual-detection fluorescent probe for copper and zinc ions and a preparation method thereof, wherein the preparation method comprises the following steps: firstly, carrying out substitution reaction on 4, 6-dichloro-5-aminopyrimidine and 1-naphthylamine to obtain an intermediate compound II; then the intermediate compound II reacts with formic acid in an organic solvent to obtain an intermediate compound III with a purine ring; then the intermediate compound III reacts with a methanol solution of amine to obtain an intermediate compound IV; and finally, carrying out condensation reaction on the intermediate compound IV and chromone-3-formaldehyde to obtain the purine matrix-based fluorescent probe. The fluorescent probe has dual recognition on zinc ions and copper ions, has short response time, and can be used for detecting Zn in solution2+And Cu2+The fluorescent probe shows high sensitivity and high selectivity, and can also detect zinc ions and copper ions in a solid stateThe product has good portability and stability.
Description
Technical Field
The invention relates to a dual-detection fluorescent probe for copper and zinc ions and a preparation method of the dual-detection fluorescent probe.
Background
Zinc ion (Zn)2+) Has good coordination function, is the second most abundant transition metal ion in human body, and is widely distributed in the nuclear fluid of human body. Zn2+The method is very interesting in the field of neurobiology, and plays an important role in enzymatic reaction and DNA synthesis in a biological system. However, excess Zn2+Can cause nervous system diseases such as epilepsy, Parkinson disease, ischemic stroke, infantile diarrhea and the like. Therefore, the method has important significance for the selective recognition and effective detection of the free zinc ions in the relevant research in the fields of chemistry, biology, clinical medicine, agriculture and the like.
Copper ion (Cu)2+) Is an indispensable metal element in organisms and plays a crucial role in the biochemistry of organisms, and most of copper ions in human bodies are combined with proteins, which are necessary metal elements for human metabolism. However, an imbalance in copper homeostasis can lead to inherited copper metabolism disorders. Therefore, the method has great significance for selective recognition and effective detection of free copper ions.
Currently, commonly used detection methods for zinc ions and copper ions include Atomic Absorption Spectroscopy (AAS), Atomic Emission Spectroscopy (AES), inductively coupled plasma mass probe, electrochemical methods, and the like, but these test methods are expensive, sample pretreatment is complicated, measurement time is relatively long, and professional operators are required.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a fluorescent probe with high selectivity and high sensitivity to zinc ions and copper ions, and also aims to provide a preparation method of the fluorescent probe.
The technical scheme is as follows: the invention relates to a dual-detection fluorescent probe for copper and zinc ions, which has the following structural formula:
the preparation method of the dual-detection fluorescent probe for copper ions and zinc ions specifically comprises the following steps: firstly, carrying out substitution reaction on 4, 6-dichloro-5-aminopyrimidine and 1-naphthylamine to obtain an intermediate compound II; then the intermediate compound II and formic acid react in an organic solvent to obtain an intermediate compound III with a purine ring; then the intermediate compound III reacts with a methanol solution of amine to obtain an intermediate compound IV; and finally, carrying out condensation reaction on the intermediate compound IV and chromone-3-formaldehyde to obtain the purine matrix-based fluorescent probe.
the intermediate compound II is prepared by the following method: sequentially adding 4, 6-dichloro-5-aminopyrimidine and 1-naphthylamine into methanol, adding concentrated hydrochloric acid after dissolving, and refluxing and stirring; and after the reaction is completed, distilling under reduced pressure to remove the organic solvent, dissolving with NaOH, extracting with ethyl acetate, distilling under reduced pressure to remove ethyl acetate, recrystallizing with methanol and water, and drying to obtain an intermediate compound II.
the intermediate compound III is prepared by the following method: respectively dissolving the intermediate compound II, acetic acid, polyphosphoric acid and dodecyl trimethyl ammonium chloride in phosphorus oxychloride, and refluxing and stirring; after the reaction is completed, cooling the reaction liquid to room temperature, distilling under reduced pressure to remove the solvent phosphorus oxychloride, adding an ice water mixture into the reaction system under the condition of an ice water bath, purifying and eluting by using MeOH/DCM (v/v,1/250) through a column chromatography method, and drying to obtain an intermediate compound III.
wherein the intermediate compound IV is prepared by adopting the following method: dissolving the intermediate compound III in a methanol solution of amine, heating and stirring, cooling the reactant to room temperature after the reaction is completed, carrying out suction filtration, washing the solid with an organic solvent, and drying to obtain an intermediate compound IV.
The reaction route of the fluorescent probe of the invention is shown as follows:
when the probe is complexed with different metal ions, the change of fluorescence intensity is different due to different binding sites. When Zn is added2+The increase in conjugation of the complex results in an increase in fluorescence intensity; when Cu is added2+In the process, ions are complexed with an imine structure, and the conjugation of the structure is destroyed, so that the fluorescence intensity is reduced. When other metal ions are added, the fluorescence intensity is not obviously changed from the fluorescence intensity of the probe, so that the fluorescent probe can not detect other metal ions, and the other metal ions basically have no interference on the detection of copper ions and zinc ions by the fluorescent probe.
The intermediate compound II and the intermediate compound III are products containing purine rings synthesized by taking pyrimidine as a basic raw material, and the compounds containing the purine rings take the purine rings as fluorescent luminescent groups, have planar rigid structures and contain rich nitrogen atoms and pi-pi conjugated systems on the one hand, so that the compounds can effectively perform coordination reaction with metal ions; and the purine ring-containing compound (intermediate compound III) reacts with amine to increase the connecting group of the amine, the hydrazone compound is an organic compound formed by condensing an amine compound and an aldehyde compound, the purine ring can be used as one end of the amine compound to condense with the aldehyde compound to form a larger conjugated system, the formed imine structure can increase the binding site with metal ions, and a larger space can be provided for accommodating the metal ions. Therefore, the hydrazone compound formed by taking the purine ring as the parent of the fluorescent probe and taking the Schiff base reaction as the basis can effectively improve the binding capacity of the fluorescent probe compound and metal ions, so that the detection lower limit value of the fluorescent probe compound on the metal ions is low.
Has the advantages that: the fluorescent probe can identify zinc ions with low concentration in the solution and copper ions with low concentration in the solution, and has short response time, thereby showing the effect of the fluorescent probe on Zn in the solution2+And Cu2+The fluorescence probe has high sensitivity and selectivity, and can detect zinc ions and copper ions in a solution in a solid state, so that the fluorescence probe has good portability and stability.
Drawings
FIG. 1 shows the fluorescent probe prepared in example 1 in DMSO-H2Zinc ion (Zn) in O (v/v ═ 9:1) solution2+) And copper ion (Cu)2+) Ultraviolet absorption spectrum of (2);
FIG. 2 shows the fluorescent probe prepared in example 1 in DMSO-H2Fluorescence spectra selective for different metal ions in O (v/v ═ 9:1) solution;
FIG. 3 shows fluorescent probes prepared in example 1 in DMSO-H2For different concentrations of zinc ion (Zn) in O (v/v ═ 9:1) solution2+) And copper ion (Cu)2+) A fluorescence spectral response map of (a);
FIG. 4 shows fluorescent probes prepared in example 1 in DMSO-H2A plot of the fluorescence response to selective interference detection of different ions in O (v/v ═ 9:1) solution;
FIG. 5 shows the fluorescent probe prepared in example 1 in DMSO-H2Neutralization of zinc ion (Zn) in O (v/v ═ 9:1) solution2+) And copper ion (Cu)2+) A Job-plot of the complex ratio;
FIG. 6 is a graph showing the change of fluorescence color when the probe strip prepared from the fluorescent probe prepared in example 1 detects zinc ions and copper ions with different concentrations;
FIG. 7 is a graph showing response times when zinc and copper ions are detected by the fluorescent probe prepared in example 1;
FIG. 8 is a MS spectrum of the fluorescent probe prepared in example 1;
FIG. 9 shows NMR of the fluorescent probe obtained in example 11H-NMR spectrum;
FIG. 10 shows NMR of the fluorescent probe obtained in example 113C-NMR spectrum.
Detailed Description
Example 1
The preparation method of the fluorescent probe for dual detection of copper ions and zinc ions comprises the following steps:
step (1), preparation of intermediate compound II: (6-chloro-N4- (naphthalen-1-yl) pyrimidine-4, 5-diamine)
Adding 50mL of methanol into a 100mL round-bottom flask, adding 4, 6-dichloro-5-aminopyrimidine (5.00g, 30mmol) and 1-naphthylamine (8.58g, 60mmol) into the flask, and adding 5mL of HCl with the concentration of 12mol/L into the flask after the materials are dissolved; the mixture was stirred under reflux at 65 ℃ for 5 days; after the reaction is completed, cooling, and then distilling under reduced pressure to remove the organic solvent methanol; dissolving all the obtained crude products in 50mL of 1M NaOH aqueous solution, extracting the mixture with ethyl acetate for 3 times, and distilling under reduced pressure to remove the ethyl acetate; washing the organic phase with 1.2M HCl, removing water with saturated saline solution, and drying to obtain a crude product; the crude product is substituted by CH3OH/H2Recrystallization from O (v/v, 1: 5) and drying afforded intermediate compound II as a pale purple solid powder (5.75g, 71% yield).
The structural formula of the obtained intermediate compound II is as follows:
intermediate compound II1H NMR(400MHz,DMSO-d6)δ8.92(s,1H),7.99–7.94(m,1H),7.92–7.87(m,1H),7.85–7.81(m,1H),7.63(s,1H),7.58–7.48(m,4H),5.52(s,2H).13C NMR(100MHz,DMSO-d6)δ151.62,145.58,138.88,135.45,134.42,129.88,128.59,126.47,126.33,126.17,126.15,124.96,123.97,123.69.
Step (2), preparation of intermediate compound iii: (6-chloro-9- (naphthalen-1-yl) -8-methyl-9H-purine)
The intermediate compound II (1.00g, 3.70mmol) obtained in step (1), acetic acid (1.11g, 18.50mmol) and DTAC (0.10g,10% mmol) in 25mL of POCl3Adding polyphosphoric acid (5.00g, 14.80mmol) into phosphorus oxychloride after the solid substances are completely dissolved; the reaction mixture was stirred at 80 ℃ under reflux for 72 hours; after the reaction is finished, cooling the reaction liquid to room temperature, and distilling under reduced pressure to remove the organic solvent to obtain brown oily matter; adding 100mL of ice-water mixture into the reaction system under the condition of ice-water bath, stirring to separate out a large amount of solid, performing suction filtration to obtain a crude product, purifying by silica gel column chromatography, and using CH3OH/CH2Cl2(v/v,1/250) and the solvent was distilled off under reduced pressure and then dried to obtain intermediate compound III as a white solid (0.46g, yield 42%).
The structural formula of the obtained intermediate compound III is as follows:
intermediate compound III1H NMR(400MHz,DMSO-d6)1H NMR(400MHz,DMSO-d6)δ8.60(s,1H),8.26(m,J=8.0,1.1Hz,1H),8.17(d,J=8.2Hz,1H),7.83–7.73(m,2H),7.68–7.66(m,1H),7.54–7.52(m,1H),7.21(dd,J=8.5,1.0Hz,1H),2.38(s,3H).13C NMR(101MHz,DMSO-d6)δ156.89,151.31,148.73,145.94,134.27,130.78,130.51,130.10,128.93,128.38,127.41,127.19,126.20,123.55,122.33,14.11.
Step (3), preparation of intermediate compound IV: (6-hydrazino-9- (naphthalen-1-yl) -8-methyl-9H-purine)
Dissolving the intermediate compound III (0.32g, 1.09mmol) obtained in the step (2) in 6mL of an amine in methanol; heating and stirring the mixed material at 65 ℃ for 3 hours; after the reaction is finished, cooling the mixture to room temperature, separating out solids, carrying out suction filtration, washing the solids for three times by using glacial methanol, and drying to obtain white powder (0.21g, yield 70%) which is an intermediate compound IV;
the structural formula of the obtained intermediate compound IV is as follows:
intermediate compound IV1H-NMR (400MHz, DMSO-d 6). delta.9.00 (s,2H), 8.20-8.19 (m,1H), 8.18-8.12 (m,1H),8.07(s,1H), 7.76-7.68 (m,2H), 7.65-7.63 (m,1H), 7.53-7.51 (m,1H), 7.06-7.64 (m,1H),2.24(s,3H).13C NMR(101MHz,DMSO-d6)δ156.86,155.05,151.87,148.05,134.34,131.03,130.98,130.02,129.81,129.02,128.53,127.56,127.44,126.27,122.34,14.11.
Step (4), preparing a fluorescent probe compound:
the intermediate compound IV (56mg, 0.2mmol) obtained in step (3) and chromone-3-carbaldehyde (37mg,0.3mmol) were dissolved in 2mL of ethanol under N2Under the protection, the mixture is refluxed and stirred for 2 hours at the temperature of 80 ℃; after completion of the reaction followed by plate spotting (TLC), the reaction mass was cooled to room temperature and the solvent was distilled off under reduced pressure; and (3) recrystallizing and purifying the crude product by using dichloromethane-methanol, adding a small amount of methanol to dissolve the crude product, adding a proper amount of dichloromethane to turbidity, placing the mixture in a refrigerator for refrigeration until crystals are separated out, performing suction filtration, and drying to obtain the dual fluorescent probe compound based on the purine matrix, wherein the fluorescent probe compound is white powder (60.4mg, 70%).
The structural formula of the obtained fluorescent probe compound is as follows:
fluorescent probe compounds of the invention1H NMR(400MHz,Chloroform-d)δ12.60(d,J=11.5Hz,1H),8.58(d,J=11.8Hz,1H),8.50(s,1H),8.10(dd,J=7.8,1.7Hz,2H),8.01(t,J=7.2Hz,1H),7.80–7.64(m,1H),7.57–7.44(m,3H),7.19–7.06(m,3H),5.81(d,J=1.7Hz,1H),2.43(s,3H).
13C NMR(101MHz,Chloroform-d)δ182.72,160.63,156.33,154.70,153.49,152.39,148.07,135.12,134.59,130.66,130.17(d,J=5.6Hz),128.71(d,J=5.9Hz),128.05(d,J=3.0Hz),127.13(d,J=7.9Hz),126.94,126.31(d,J=2.2Hz),125.57,122.81,122.30,121.79(d,J=3.3Hz),120.76,118.62,118.15,108.24,101.75,14.45.
Practice ofMass spectrum MS spectrogram and nuclear magnetic resonance of fluorescent probe prepared in example 11H-NMR spectrum, nuclear magnetic resonance13The C-NMR spectra are shown in FIG. 8, FIG. 9 and FIG. 10, respectively, and illustrate the successful synthesis of the fluorescent probe of the present invention.
Example 2
The fluorescent probe prepared in example 1 was prepared as a 1mM stock solution in DMSO (dimethyl sulfoxide), each metal ion was prepared as a 3mM stock solution in deionized water, and 3mL of a blank DMSO-H solution was added2Adding 30 mu L of probe stock solution and 50 mu L of metal ion stock solution into O (v/v is 9:1), detecting by using a fluorescence spectrometer and an ultraviolet spectrophotometer, and testing to obtain that the maximum excitation wavelength of the fluorescence probe is 388nm and the maximum emission wavelength is 468nm, wherein the specific test results are as follows:
taking two cuvettes, adding 3mL of blank solution DMSO-H into each cuvette2O (v/v ═ 9:1) and 30 μ L of the probe stock solutions, 50 μ L of the zinc ion or copper ion stock solution was added to one of the cuvettes, and the other cuvette was not added with the zinc ion or copper ion stock solution, and the uv spectrum test was performed. As shown in fig. 1, the fluorescent probe compound itself has strong ultraviolet absorption at a wavelength λ of 375nm, and when zinc ions are added to the solution, the ultraviolet absorption peak gradually decreases, and when copper ions are added to the solution, the ultraviolet absorption peak is red-shifted, and thus, strong ultraviolet absorption at a wavelength λ of 446nm occurs. The result shows that the fluorescent probe of the invention is directed to Zn2+And Cu2+All have high sensitivity (probe to Zn)2+Detection limit of (2) was 23nM for Cu2+Has a detection limit of 154 nM).
FIG. 2 is a graph showing fluorescence spectra of fluorescent probes to which various metal ions were added. To 3mL of blank solution DMSO-H2The result of adding 30 mul of probe stock solution and 50 mul of various metal ion stock solution into O (v/v ═ 9:1) shows that the fluorescence color of the probe solution is changed from colorless to light yellow when zinc ions are added, the fluorescence intensity of the fluorescence spectrum at 468nm is obviously enhanced, the fluorescence color of the probe solution is changed from colorless to dark yellow when copper ions are added, and the fluorescence intensity of the fluorescence spectrum at 468nm is obviously enhancedAnd when other metal ions are added, the fluorescence color of the probe solution has no obvious change, which shows that the fluorescent probe has good selectivity on zinc ions and copper ions.
FIG. 3 shows fluorescent probes for different concentrations of Zinc ion (Zn)2+) And copper ion (Cu)2+) Fluorescence spectral response map of (a). To 3mL of blank solution DMSO-H2Adding 30 mu L of probe stock solution and 0-100 mu L of zinc ion or 0-50 mu L of copper ion solution (3mM of zinc or copper ion stock solution) into O (v/v ═ 9:1), wherein the fluorescent probe is colorless in a blank solution, but the fluorescence is continuously enhanced at 468nm along with the increase of the concentration of zinc ions, which shows that the fluorescence intensity is increased along with the increase of the concentration of zinc ions; the fluorescence also decreased continuously at 468nm with increasing copper ion concentration, indicating that the fluorescence intensity decreased with increasing copper ion concentration.
FIG. 4 is a bar graph of fluorescence intensity of fluorescent probes after reaction with zinc ions or copper ions in the presence of different interfering metal ions. To 3mL of blank solution DMSO-H2To O (v/v-9: 1) were added 30. mu.L of the probe stock solution and 50. mu.L of any other metal ion (Co)2+,Ni2+,Al3+,Cr3+,Mn2+,Mg2+,Pb2+,K+,Ca2+,Cs2+,Na+,Ag+,Cd2+,Pd2+And Fe3+) Stock solution, to which 50. mu. LZn was added2+Or Cu2+Stock solutions were tested for fluorescence intensity. The results show that Cr3+、Fe3+And Al3+Has certain influence on the fluorescent probe, and the existence of other metal ions has no obvious interference on the fluorescent probe compound for identifying zinc ions and copper ions.
Probes with Zn were studied by the Job's plot method2+And Cu2+Binding rate of (2), to 3mL of blank solution DMSO-H2Adding a certain volume of probe stock solution and Zn into O (v/v ═ 9:1)2+Or Cu2+Stock solution (3mM) was prepared so that the sum of the concentrations of the fluorescent probe and zinc ion or copper ion was 50. mu.M, by changing the concentration ratio of the fluorescent probe and zinc ion or copper ion species (amount of fluorescent probe and zinc ion or copper ion species)The ratio of the above-mentioned two components is 1: 9, 2: 8, 3: 7, 4: 6, 5: 5, 6: 4, 7: 3, 8: 2, 9:1) in this order, the difference between the fluorescence intensity at 468nm and the fluorescence intensity of the fluorescence probe at that concentration (zinc ion detection) is obtained, and the copper ion detection is carried out by obtaining the difference between the ultraviolet intensity at 446nm and the ultraviolet intensity of the probe at that concentration and plotting the ratio of the ion to the total concentration. From this FIG. 5, it can be seen that when the ratio of zinc ions is 0.7, the ordinate reaches the maximum value, it can be determined that the fluorescent probe compound and zinc ions are mainly combined in a 1: 2 form to form a stable complex, and when the ratio of copper ions is 0.5, the ordinate reaches the maximum value, it can be determined that the fluorescent probe compound and copper ions are mainly combined in a 1: 1 form to form a stable complex.
As shown in fig. 6, the filter paper was immersed in the stock solution containing the fluorescent probe for half an hour, and then the test strip was taken out and dried in the air to obtain a dried test strip containing the probe. The test strips are respectively soaked in zinc ion or copper ion solutions with the concentrations of 0mM, 0.5mM and 1mM, the test strips are soaked for a few minutes and then dried, and quick color change strips shown in figure 6 are observed under a 365nm ultraviolet lamp, which shows that the probe can detect the zinc ions and the copper ions in a solid state.
As shown in FIG. 7, 3mL of blank buffer DMSO-H was added2O (v/v-9: 1) was added with 30. mu.L of the probe stock solution and 50. mu.L of Zn2+Or Cu2+The fluorescence intensity of the probe rapidly increases to the maximum or rapidly decreases to the minimum in the stock solution, and the fluorescence intensity gradually decreases and becomes stable within 10 minutes by adding zinc ions, which indicates that the probe has Zn resistance2+The detection is stable enough and the speed is high; when copper ions were added, the fluorescence intensity decreased and tended to be stable within 1 minute, indicating that the probe was resistant to Cu2+The detection is stable enough and fast.
Claims (8)
2. the method for preparing the fluorescent probe for dual detection of copper ions and zinc ions as claimed in claim 1 is characterized by comprising the following steps: firstly, carrying out substitution reaction on 4, 6-dichloro-5-aminopyrimidine and 1-naphthylamine to obtain an intermediate compound II; then the intermediate compound II reacts with formic acid in an organic solvent to obtain an intermediate compound III with a purine ring; then the intermediate compound III reacts with a methanol solution of amine to obtain an intermediate compound IV; and finally, carrying out condensation reaction on the intermediate compound IV and chromone-3-formaldehyde to obtain the purine matrix-based fluorescent probe.
4. the method for preparing the fluorescent probe for dual detection of copper and zinc ions according to claim 3, wherein the intermediate compound II is prepared by the following method: sequentially adding 4, 6-dichloro-5-aminopyrimidine and 1-naphthylamine into methanol, adding concentrated hydrochloric acid after dissolving, and refluxing and stirring; and after the reaction is completed, distilling under reduced pressure to remove the organic solvent, dissolving with NaOH, extracting with ethyl acetate, distilling under reduced pressure to remove ethyl acetate, recrystallizing with methanol and water, and drying to obtain an intermediate compound II.
6. the method for preparing the fluorescent probe for dual detection of copper and zinc ions according to claim 5, wherein the intermediate compound III is prepared by the following method: respectively dissolving an intermediate compound II, acetic acid, polyphosphoric acid and dodecyl trimethyl ammonium chloride in phosphorus oxychloride, and refluxing and stirring; and after the reaction is completed, cooling the reaction liquid to room temperature, carrying out reduced pressure distillation to remove the organic solvent, adding an ice-water mixture into the reaction system under the condition of ice-water bath, purifying, eluting and drying to obtain an intermediate compound III.
8. the method for preparing the fluorescent probe for dual detection of copper and zinc ions according to claim 7, wherein the intermediate compound IV is prepared by the following method: dissolving the intermediate compound III in a methanol solution of amine, heating and stirring, cooling the reactant to room temperature after the reaction is completed, carrying out suction filtration, washing the solid with an organic solvent, and drying to obtain an intermediate compound IV.
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