CN113004186B - Zinc-ligand azapyrrolidone photo-diagnosis and treatment reagent with long-wave absorption characteristic and preparation and application thereof - Google Patents
Zinc-ligand azapyrrolidone photo-diagnosis and treatment reagent with long-wave absorption characteristic and preparation and application thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 238000011282 treatment Methods 0.000 title claims abstract description 24
- 238000010521 absorption reaction Methods 0.000 title claims abstract description 23
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 14
- 239000003446 ligand Substances 0.000 title claims abstract description 13
- 238000003745 diagnosis Methods 0.000 title claims abstract description 12
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 29
- 239000011701 zinc Substances 0.000 claims abstract description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- 239000000243 solution Substances 0.000 claims description 32
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 28
- 239000007787 solid Substances 0.000 claims description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 14
- 238000005406 washing Methods 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 12
- 229940125782 compound 2 Drugs 0.000 claims description 10
- 229940126214 compound 3 Drugs 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- -1 zinc-diaza-pyrrolidone Chemical compound 0.000 claims description 8
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 6
- 239000005695 Ammonium acetate Substances 0.000 claims description 6
- 229940043376 ammonium acetate Drugs 0.000 claims description 6
- 235000019257 ammonium acetate Nutrition 0.000 claims description 6
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 6
- 230000007935 neutral effect Effects 0.000 claims description 6
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 5
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 2
- 238000004821 distillation Methods 0.000 claims 2
- 238000010438 heat treatment Methods 0.000 claims 2
- 230000001376 precipitating effect Effects 0.000 claims 2
- DGPBVJWCIDNDPN-UHFFFAOYSA-N 2-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=CC=C1C=O DGPBVJWCIDNDPN-UHFFFAOYSA-N 0.000 claims 1
- 230000008859 change Effects 0.000 abstract description 5
- 230000005284 excitation Effects 0.000 abstract description 4
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- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 7
- ZKSVYBRJSMBDMV-UHFFFAOYSA-N 1,3-diphenyl-2-benzofuran Chemical compound C1=CC=CC=C1C1=C2C=CC=CC2=C(C=2C=CC=CC=2)O1 ZKSVYBRJSMBDMV-UHFFFAOYSA-N 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
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- 230000002140 halogenating effect Effects 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 2
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- 241000282414 Homo sapiens Species 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 1
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- 238000011228 multimodal treatment Methods 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
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Abstract
The invention discloses a zinc ligand azapyrrolidone photo-diagnosis and treatment reagent with long wave absorption characteristics, and preparation and application thereof. The light diagnosis and treatment reagent consists of a metal center and an azapyrrolidone auxiliary ligand, the whole preparation process is simple, and the prepared complex has longer absorption wavelength which can be prolonged along with the change of the azapyrrolidone auxiliary ligand, so that the light diagnosis and treatment reagent has deeper tissue penetration depth in the field of living body application; can be excited by near infrared light and has near infrared light emission, thereby weakening the damage of the excitation light source to the biological sample; the complex can be used in the field of photodynamic photo-thermal combined treatment guided by biological imaging, and has important application prospect.
Description
Technical Field
The invention belongs to the technical field of organic photoelectric and biological materials. In particular to a zinc-dipyrazone-based photo-diagnosis and treatment reagent with a near-infrared absorption function, a preparation method thereof, and applications thereof in the fields of fluorescence imaging, photo-thermal imaging, photo-acoustic imaging, photodynamic and photo-thermal combined treatment and the like.
Background
The tumor is a disease with high fatality rate and seriously threatens the health of human beings. Traditional tumor treatment methods, such as surgery, chemotherapy, radiotherapy and the like, have certain effect on tumor treatment, but are often accompanied by side effects in the implementation process. In contrast, photodynamic and photothermal combined therapy is increasingly favored as a non-invasive, non-toxic, targeted and efficient tumor treatment means, and the therapy can accurately treat tumor parts in real time, so that the tumor treatment effect is greatly improved. The selection of the photodynamic and photothermal combined treatment material has a decisive effect on the effect of the photodynamic and photothermal combined treatment. Therefore, how to select the ideal photodynamic and photothermal combined therapy material has attracted extensive attention in the industry.
Metal complexes have been widely used in multimodal tumor therapy in recent years. However, due to the short absorption wavelength of the metal complex, additional compounds are required to be introduced to achieve multimodal treatment, and most of the metal complexes used for tumor treatment are mostly prepared from noble metals. Therefore, the metal complex has the defects of low penetration depth, complex preparation process and high price in the field of tumor treatment, and further expansion and application of the material in the field of tumor treatment are severely restricted. Therefore, the development of novel inexpensive metal complexes having long-wavelength absorption and simultaneously having a multimodal therapeutic function is the focus of research.
Azapyrrolidone dyes can be coordinated with zinc ions due to a suitable NN ligand, and are used in the fields of biomarkers, imaging, photodynamic therapy and the like, and few reports have been made so far on designing and synthesizing zinc-coordinated azapyrrolidone dyes with good photothermal effects by utilizing effective theoretical guidance. Based on the theoretical guidance of photoinduced electron transfer and the excellent performance of the aza-fluoroborane dye, the invention connects electron donating groups to the aza-pyrrolidone dye with near infrared absorption, thereby leading the dye to have good photoacoustic imaging, photothermal imaging and photothermal treatment effect of biological tumors. The zinc-coordinated azapyrrolidone dye can also form a molecular structure with high photodynamic effect of a D-A-D structure through intramolecular charge transfer.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides a zinc-azapyrrolidone diagnosis and treatment reagent with long-wave absorption characteristics and a preparation method and application thereof.
The technical scheme of the invention is as follows: a zinc ligand azapyrrolidone light diagnosis and treatment reagent with long wave absorption characteristics has the following structural general formula:
wherein R is 1 、R 2 、R 4 、R 5 Is any one of the following: :
wherein R is 3 Is H or a linear, branched or cyclic alkyl alkane having 1 to 16 carbon atoms;
wherein, X 1 、X 2 Is H, cl, br or I.
The preparation route of the zinc-aza-pyrrolidone photo-diagnosis reagent with the long-wave absorption characteristic is as follows:
the specific synthesis steps are as follows:
1)R 1 with R 2 Dissolving the ketone in methanol solution, carrying out aldehyde ketone condensation reaction in the presence of NaOH, adjusting the pH value to be neutral, filtering to remove the methanol solvent, and washing to obtain a compound 1;
2) Reacting the compound 1 with nitromethane and diethylamine in methanol for a certain time, removing the solvent by spin-drying, dissolving in ethanol, filtering and washing to obtain a compound 2;
3) Dissolving the compound 2 in n-butyl alcohol solution, adding ammonium acetate, stirring for reaction for a period of time, distilling under reduced pressure to remove n-butyl alcohol, and washing with cold ethanol to obtain a compound 3;
4) Dissolving the compound 3 in a chloroform solution, and sequentially adding acetic acid and a halogenating raw material to obtain a compound 4;
5)R 5 aldehyde of (A) with R 4 Dissolving the ketone in methanol solution, carrying out aldehyde ketone condensation reaction in the presence of NaOH, adjusting the pH value to be neutral, filtering to remove the methanol solvent, and washing to obtain a compound 5;
6) Reacting the compound 5 with nitromethane and diethylamine in methanol for a certain time, removing the solvent by spin-drying, dissolving in ethanol, filtering, and washing to obtain a compound 6;
7) Dissolving the compound 6 in n-butyl alcohol solution, adding ammonium acetate, stirring for reaction for a period of time, distilling under reduced pressure to remove n-butyl alcohol, and washing with cold ethanol to obtain a compound 7;
8) Dissolving the compound 7 in a chloroform solution, and sequentially adding acetic acid and a halogenating raw material to obtain a compound 8;
9) Dissolving the compound 4 and the compound 8 in a mixed solution of acetic acid, methanol and water, then adding zinc acetate, stirring at room temperature, and spin-drying the reaction solution to obtain the final product of zinc-aza-pyrrolidone.
Further, in step 9), the molar ratio of compound 4 to compound 8 is 1:1.
Further, in step 9), the volume ratio of acetic acid, methanol and water is 3.
The zinc-ligand azapyrrolidone photo-diagnosis reagent with the long-wave absorption characteristic can generate singlet oxygen with cytotoxicity through laser irradiation; the light diagnosis and treatment reagent has longer absorption wavelength and can be used for biological fluorescence imaging, biological photothermal imaging, biological photoacoustic imaging and time resolution imaging.
The invention has the beneficial effects that:
the zinc-nitrogen-doped pyrrolidone complex disclosed by the invention has long wave absorption, so that the zinc-nitrogen-doped pyrrolidone complex can have a deeper tissue penetration depth in the field of living body application;
the zinc-ligand azapyrrolidone complex disclosed by the invention can be excited by near infrared light and has near infrared light emission, so that the damage of an excitation light source to a biological sample can be reduced;
the zinc ligand azapyrrolidone complex disclosed by the invention can be applied to biological imaging and photothermal and photodynamic combined treatment and has better photothermal and photodynamic effects.
Drawings
FIG. 1 is a mass spectrum of ZnDipy-1, a zinc complex prepared in example one;
FIG. 2 is a nuclear magnetic hydrogen spectrum of ZnDipy-1, a zinc complex prepared in the first example;
FIG. 3 is a UV-VIS absorption spectrum of the zinc complex ZnDipy-1 prepared in the first example;
FIG. 4 is a photothermal diagram of the zinc complex ZnDipy-1 prepared in example one;
FIG. 5 is a photodynamic diagram of the zinc complex ZnDipy-1 prepared in example one;
FIG. 6 is a mass spectrum of ZnDipy-2, a zinc complex prepared in example two;
FIG. 7 is a nuclear magnetic hydrogen spectrum of the zinc complex ZnDipy-2 prepared in example two;
FIG. 8 is a UV-VIS absorption spectrum of the zinc complex ZnDipy-2 prepared in example two;
FIG. 9 is a photothermographic view of the zinc complex ZnDipy-2 prepared in example two;
FIG. 10 is a photodynamic diagram of the zinc complex ZnDipy-2 prepared in example two.
Detailed Description
The following examples further illustrate the present invention but are not to be construed as limiting the invention. Modifications and substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit of the invention.
The first embodiment is as follows: preparation of zinc-nitrogen-doped pyrrolidone complex with long-wave absorption performance
1. Preparation of azapyrrolidone ancillary ligands
Preparation of compound 2: compound 1 (26 mmol) and benzaldehyde (26 mmol) were dissolved in sodium methoxide solution, followed by addition of 50% by mass aqueous NaOH solution, stirring at room temperature for reaction for 22 hours, pH was adjusted to neutral, and methanol solvent was removed by filtration to give pale yellow solid powder, which was then washed three times with water to remove salts to give white product 2. Yield: 91 percent.
1 H NMR(400MHz,CDCl 3 )δ(ppm):8.01(d,J＝8.4Hz,2H),7.78(d,J＝16.4Hz,1H),7.53(d,J＝8.4Hz,2H),7.35(d,J＝16.4Hz,2H),6.98(d,J＝8.4Hz,2H),6.69(d,J＝8.4Hz,2H),3.66(s,6H). 13 C NMR(100MHz,CDCl 3 )δ(ppm):188.85,169.10,162.20,151.91,144.95,131.97,130.49,130.27,122.82,116.63,114.27.
Preparation of compound 3: after 10mL of diethylamine and 15mL of nitromethane were added to a methanol solution of Compound 2 (5 mmol), and heated under reflux for 24 hours, the solvent was removed by rotary drying and the solid was dissolved in 30mL of ethanol, and a large amount of white solid precipitated, which was obtained by filtration and washed three times with diethyl ether and water to obtain white solid 3. Yield: 83 percent.
1 H NMR(400MHz,CDCl 3 )δ(ppm):8.01(d,J＝8.8Hz,2H),7.78(d,J＝15.2Hz,1H),7.55(d,J＝8.8Hz,2H),7.35(d,J＝15.6Hz,2H),6.98(d,J＝8.8Hz,2H),6.69(d,J＝8.8Hz,2H),4.81–4.60(m,2H),4.18–4.11(m,1H),3.68(s,6H),. 13 C NMR(100MHz,CDCl 3 )δ(ppm):188.85,162.20,151.91,144.95,131.97,130.49,130.27,122.82,116.63,111.83,71.92,70.81.
Preparation of compound 4: dissolving compound 3 (2.50 mmol) and 20g ammonium acetate in n-butanol solution, stirring and refluxing at 120 deg.C overnight, distilling under reduced pressure to remove n-butanol after reaction, and washing residual solid with cold ethanol to obtain black solid 4. The yield was 69%.
2. Preparation of zinc complex azapyrrolidone complex ZnDipy-1
Preparation of compound ZnDipy-1: compound 4 (1.00 mmol) was dissolved in acetic acid: methanol: to a mixed solution of water = 3. And finally, spin-drying the reaction solution, and passing the reaction solution through a column to obtain a black solid ZnDipy-1.
1 H NMR(400MHz,CDCl 3 )δ(ppm):7.95(d,J＝7.2Hz,8H),7.46(d,J＝8.8Hz,8H),7.40(t,J＝7.4Hz,8H),7.32(t,J＝6.6Hz,4H),6.71(s,4H),6.39(d,J＝8.8Hz,8H),2.69(s,24H).[m/e](M, MALDI-TOF) theoretical value 1134.75 and experimental value 1134.60.
And (4) relevant performance test:
1. the mass spectrum of the zinc complex ZnDipy-1 is shown in figure 1.
2. The hydrogen nuclear magnetic resonance spectrum of the zinc complex ZnDipy-1 is shown in figure 2.
3. And (3) testing the absorption spectrum of the zinc complex ZnDipy-1:
the concentration of the spectrum test used was 10. Mu.M, and the test solvent was CH 2 Cl 2 When the emission spectrum of the solution (2) is measured, the excitation wavelength is 667 (753) nm.
The ultraviolet-visible absorption spectrum of the zinc complex ZnDipy-1 is shown in FIG. 3.
The complex shows stronger absorption in 400-500nm of ultraviolet region and 600-800nm of near infrared region, especially the complex can be excited by near infrared light, thus greatly reducing the damage of exciting light source to cells when cell imaging experiment is carried out.
Photothermal Effect test of ZnDipy-1
ZnDipy-1 prepared in example 1 was dissolved in THF, diluted to different concentration gradient solutions (0, 5, 10. Mu.M) with PBS buffer solution pH =7.4, irradiated with 660nm laser for 6min (0.4W/cm) 2 ) And recording the change of the solution temperature at different time and different concentration by using a photo-thermal imaging instrument. The photothermal graph of the zinc complex ZnDipy-1 is shown in figure 4, and figure 4 shows that the maximum change of the solution temperature is up to 25 ℃ along with the increase of the concentration, so that the zinc complex ZnDipy-1 has a better photothermal effect.
Photodynamic effect of ZnDipy-1
ZnDipy-1 prepared in example 1 was dissolved in THF, the generation of singlet oxygen was demonstrated with the singlet oxygen indicator DPBF, the 660nm laser was used to irradiate for different times, and the changes in the absorption peaks of DPBF at different irradiation times (0 min, 1min, 2min, 3min, 4min, 5min, 6min, 7min, 8min, 9 min) were recorded by UV-visible spectroscopy. The photodynamic graph of the zinc complex ZnDipy-1 is shown in FIG. 5, and FIG. 5 shows that the indicator DPBF is consumed as the irradiation time is prolonged, thus demonstrating the generation of singlet oxygen.
EXAMPLE II preparation of a Zinc Diazapyrrolidone Complex with Long wave absorption Properties
1. Preparation of azapyrrolidone ancillary ligands
Preparation of compound 2: after compound 1 (26 mmol) and acetophenone (26 mmol) were dissolved in sodium methoxide solution and then 50% by mass aqueous NaOH solution was added and stirred at room temperature for reaction for 22 hours, the pH was adjusted to neutral, the methanol solvent was removed by filtration to give pale yellow solid powder, which was then washed three times with water to remove salts to give white product 2. Yield: 91 percent.
1 H NMR(400MHz,CDCl 3 )δ(ppm):7.93(d,J＝8.4Hz,2H),7.62(d,J＝16.4Hz,1H),7.44(d,J＝8.4Hz,2H),7.31(d,J＝16.4Hz,2H),6.90(d,J＝8.4Hz,2H),6.64(d,J＝8.4Hz,2H),3.76(s,6H). 13 C NMR(100MHz,CDCl 3 )δ(ppm):189.43,170.22,164.11,150.83,143.11,132.56,131.88,131.00,124.50,118.17,112.45.
Preparation of compound 3: after 10mL of diethylamine and 15mL of nitromethane were added to a methanol solution of Compound 2 (5 mmol), and heated under reflux for 24 hours, the solvent was removed by rotary drying and the solid was dissolved in 30mL of ethanol, and a large amount of white solid precipitated, which was obtained by filtration and washed three times with diethyl ether and water to obtain white solid 3. Yield: 83 percent.
1 H NMR(400MHz,CDCl 3 )δ(ppm):8.15(d,J＝8.8Hz,2H),7.90(d,J＝15.2Hz,1H),7.63(d,J＝8.8Hz,2H),7.44(d,J＝15.6Hz,2H),7.02(d,J＝8.8Hz,2H),6.80(d,J＝8.8Hz,2H),4.73–4.48(m,2H),4.07–3.99(m,1H),3.60(s,6H). 13 C NMR(100MHz,CDCl 3 )δ(ppm):189.76,166.33,154.22,146.61,133.54,130.27,123.95,115.90,113.64,110.80,72.41,71.04.
Preparation of compound 4: dissolving compound 3 (2.50 mmol) and 20g ammonium acetate in n-butanol solution, stirring and refluxing at 120 deg.C overnight, distilling under reduced pressure to remove n-butanol after reaction is finished, and washing the residual solid with cold ethanol to obtain black solid 4. The yield was 69%.
2. Preparation of zinc complex azapyrrolidone complex ZnDipy-2
Preparation of compound ZnDipy-2: compound 4 (1.00 mmol) was dissolved in acetic acid: methanol: to a mixed solution of water = 3. And finally, spin-drying the reaction solution, and passing through a column to obtain a black solid ZnDipy-2.
1 H NMR(400MHz,CDCl 3 )δ(ppm):7.90(d,J＝8.8Hz,8H),7.50(d,J＝6.4Hz,8H),7.10–7.01(m,12H),6.82(d,J＝8.4Hz,8H),6.60(s,4H),3.10(s,24H).[m/e](M, MALDI-TOF) theoretical value 1134.75 and experimental value 1132.44.
Correlation performance testing
1. The mass spectrum of the zinc complex ZnDipy-2 is shown in FIG. 6.
2. The nuclear magnetic hydrogen spectrum of the zinc complex ZnDipy-2 is shown in FIG. 7.
3. Absorption spectrum test of zinc complex ZnDipy-2
The concentration of the spectrum test adopted by the invention is 10 mu M, and the test solvent is CH 2 Cl 2 The excitation wavelength of the solution of (1) is 632nm when the emission spectrum is measured.
The ultraviolet-visible absorption spectrum of the zinc complex ZnDipy-2 is shown in FIG. 8.
The complex shows stronger absorption in 400-500nm of ultraviolet region and 600-800nm of near infrared region, especially the complex can be excited by near infrared light, thus greatly reducing the damage of exciting light source to cells when cell imaging experiment is carried out.
Photothermal Effect test of ZnDipy-2
ZnDipy-2 prepared in example 2 was dissolved in THF, diluted to different concentration gradient solutions (0, 20, 40. Mu.M) with PBS buffer solution pH =7.4, irradiated with a 635nm laser for 6min (0.5W/cm) 2 ) And recording the change of the solution temperature at different time and different concentration by using a photo-thermal imaging instrument. The photothermal graph of the zinc complex ZnDipy-2 is shown in FIG. 9, and the graph in FIG. 9 shows that the maximum change of the solution temperature is as high as 24 ℃ along with the increase of the concentration, so that the solution has better photothermal effect.
And 5, testing the photodynamic effect of ZnDipy-2.
ZnDipy-2 prepared in example 2 was dissolved in THF, singlet oxygen generation was demonstrated with the singlet oxygen indicator DPBF, and changes in the absorption peak of DPBF at different irradiation times (0 s, 10s, 20s, 30s, 40s, 50s, 60s, 70s, 80 s) were recorded by UV-visible spectroscopy at different times of irradiation with 660nm laser irradiation. The photodynamic graph of the zinc complex ZnDipy-2 is shown in FIG. 10. As shown in fig. 10, the indicator DPBF was consumed with the increase of the irradiation time, demonstrating the generation of singlet oxygen.
The foregoing illustrates and describes the principles, general features, and advantages of the present invention. However, the above description is only an example of the present invention, the technical features of the present invention are not limited thereto, and any other embodiments that can be obtained by those skilled in the art without departing from the technical solution of the present invention should be covered by the claims of the present invention.
Claims (3)
1. The zinc ligand aza pyrrolidone light diagnosis and treatment reagent with the long wave absorption characteristic is characterized in that the structural formula is as follows:
2. the preparation method of the zinc-diaza-pyrrolidone photo-therapeutic reagent with long wave absorption characteristic as claimed in claim 1, wherein the synthetic route of ZnDIPY-1 is as follows:
the preparation process comprises the following steps:
(1) Preparation of compound 2: dissolving 26mmol of compound 1 and 26mmol of benzaldehyde in a sodium methoxide solution, adding a 50% NaOH aqueous solution, stirring at room temperature for reaction for 22 hours, adjusting the pH to be neutral, filtering to remove the methanol solvent to obtain light yellow solid powder, washing with water for three times, and removing salts to obtain a white product 2;
(2) Preparation of compound 3: adding 10mL of diethylamine and 15mL of nitromethane into 5mmol of compound 2 in methanol, heating and refluxing for 24 hours, removing the solvent by spin drying, dissolving the solid in 30mL of ethanol, precipitating a large amount of white solid, filtering to obtain the white solid, and washing with diethyl ether and water for three times to obtain a white solid 3;
(3) Preparation of compound 4: dissolving 2.50mmol of compound 3 and 20g of ammonium acetate in n-butanol solution, stirring and refluxing at 120 ℃ overnight, removing n-butanol by reduced pressure distillation after the reaction is finished, and washing the residual solid with cold ethanol to obtain a black solid 4;
(4) Preparation of compound ZnDIPY-1: 1.00mmol of Compound 4 in V Acetic Acid (AA): methanol: water (W) To a mixed solution of = 3.
3. The preparation method of the zinc-diazepidone photodiagnosis and treatment reagent with long-wave absorption characteristic according to claim 1, wherein the synthetic route of ZnDIPY-2 is as follows:
the preparation process comprises the following steps:
(1) Preparation of compound 2: dissolving 26mmol of acetophenone and 26mmol of dimethylaminobenzaldehyde in a sodium methoxide solution, then adding a 50% NaOH aqueous solution, stirring and reacting at room temperature for 22 hours, adjusting the pH to be neutral, filtering to remove a methanol solvent to obtain light yellow solid powder, then washing with water for three times, and removing salts to obtain a white product 2;
(2) Preparation of compound 3: adding 10mL of diethylamine and 15mL of nitromethane into 5mmol of compound 2 in methanol, heating and refluxing for 24 hours, removing the solvent by rotary drying, dissolving the solid in 30mL of ethanol, precipitating a large amount of white solid, filtering to obtain the white solid, and washing with diethyl ether and water for three times to obtain a white solid 3;
(3) Preparation of compound 4: dissolving 2.50mmol of compound 3 and 20g of ammonium acetate in n-butanol solution, stirring and refluxing at 120 ℃ overnight, removing n-butanol by reduced pressure distillation after the reaction is finished, and washing the residual solid with cold ethanol to obtain a black solid 4;
(4) Preparation of compound ZnDIPY-2: 1.00mmol of Compound 4 in V Acetic acid: methanol: water (W) To a mixed solution of = 3.
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Non-Patent Citations (4)
| Title |
|---|
| Homoleptic, Four-Coordinate Azadipyrromethene Complexes of d10 Zinc and Mercury;Thomas S. Teets 等;《Inorg. Chem.》;20080227;第47卷;第2338-2346页 * |
| Photonics of boron(III) and zinc(II) dipyrromethenates as active media for modern optical devices;R.T. Kuznetsova等;《Journal of Molecular Liquids》;20190111;第278卷;第5–11页 * |
| R.T. Kuznetsova等.Photonics of boron(III) and zinc(II) dipyrromethenates as active media for modern optical devices.《Journal of Molecular Liquids》.2019,第278卷第5–11页. * |
| Thomas S. Teets 等.Homoleptic, Four-Coordinate Azadipyrromethene Complexes of d10 Zinc and Mercury.《Inorg. Chem.》.2008,第47卷第2338-2346页. * |
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