CN116789676A - Synthesis method and application of novel photosensitizer - Google Patents

Synthesis method and application of novel photosensitizer Download PDF

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CN116789676A
CN116789676A CN202310634668.0A CN202310634668A CN116789676A CN 116789676 A CN116789676 A CN 116789676A CN 202310634668 A CN202310634668 A CN 202310634668A CN 116789676 A CN116789676 A CN 116789676A
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piperidine
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晏佳莹
王璇
张诺诺
张驰
王龙
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China Three Gorges University CTGU
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    • A—HUMAN NECESSITIES
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    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
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    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
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    • C09K2211/1059—Heterocyclic compounds characterised by ligands containing three nitrogen atoms as heteroatoms

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Abstract

The invention discloses a synthesis method and application of a novel photosensitizer, wherein the structure of the photosensitizer is as follows:wherein the substituent R is any one selected from bromine, N-dimethylaminophenyl and p-cyanophenyl. The photosensitizer is prepared by taking indole derivatives and pyrrole-2-formaldehyde derivatives as raw materials, catalyzing and condensing with piperidine and acetic acid and coupling with phenylboronic acid, and has the advantages of simple synthesis method, convenient separation and purification and higher yield. The aromatic ring is introduced through cross coupling reaction, so that the conjugation of the molecules is increased, and absorption and emission spectrum red shift can promote the generation of singlet oxygen.

Description

Synthesis method and application of novel photosensitizer
Technical Field
The invention relates to a synthesis method and application of a photosensitizer, in particular to a synthesis method and application of a novel photosensitizer.
Background
Compared with fluorescein, rhodamine or cyanine dye, the boron fluoride dipyrrole fluorescent dye has the advantages of higher selectivity, high sensitivity, good optical stability and insensitivity to PH, and is widely applied to biological markers, fluorescent probes and biological imaging. Photodynamic therapy (PDT) has become an effective alternative to cancer treatment today, as PDT can achieve controlled ablation of tumor cells by modulating the incident light. Photosensitizers as the most important substance in PDT, especially photosensitizers based on organic fluorescent compounds, play a vital role in the efficacy of PDT. The photosensitizer can be activated under light irradiation to collect toxic active oxygen to degrade tumor or cancer mass, and its fluorescence signal can also be used for dynamically monitoring tumor state. Traditional organic fluorescent photosensitizers, such as porphyrin derivatives and phthalocyanine derivatives, tend to have low tumor specificity, and non-specific uptake in normal tissues can cause unnecessary side effects. Therefore, it is necessary to develop a fluorescent molecule having low side effects and high singlet oxygen generation efficiency. The invention aims at the problems, and the synthesis method and the application of the photosensitizer can generate singlet oxygen in living cells so as to kill cancer tumors, and have the advantages of easiness in detection, sensitive response, wide detection range and the like.
Disclosure of Invention
The invention mainly aims at providing a synthesis method and application of a photosensitizer.
The technical scheme of the invention is as follows:
a synthesis method and application of photosensitizer, the chemical structural formula of the compound is:
wherein the substituent R is any one selected from bromine, N-dimethylaminophenyl and p-cyanophenyl. Preferably, the chemical structural formula of the compound is as follows:
any one of the following.
The synthesis method and application of the photosensitizer comprise the following synthesis paths:
the method comprises the following steps:
(1) Adding a compound 1, toluene or DMF into a reaction bottle at room temperature, stirring for dissolution, adding a compound 2, piperidine and acetic acid, and heating for reflux to obtain a reaction solution;
(2) And (3) performing rotary evaporation on the reaction liquid in the step (1), and separating by silica gel column chromatography to obtain a product I-1.
(3) Respectively adding 1, 4-dioxane and 3 into the compound I-1 in the step (2), stirring and dissolving, adding tetra-triphenylphosphine palladium or bis (triphenylphosphine) palladium dichloride or palladium acetate, and heating to obtain a reaction solution;
(4) And (3) respectively washing, extracting, drying, concentrating and purifying the reaction liquid in the step (3) to obtain a product I, namely the novel photosensitizer.
Compound 1 is an indole derivative, and compound 2 is a pyrrole-2-formaldehyde derivative; the feeding mole ratio of the compound 1 to the compound 2 is 1:1-10.
The feeding sequence of the step (1) is that the compound 1, toluene or DMF, the compound 2, piperidine, acetic acid, piperidine and acetic acid all play the role of activating reactants, and the last addition is needed. The feeding ratio of the compound 1 to the piperidine is 1:1-10; the feeding ratio of the compound 1 to the acetic acid is 1:1-10.
The heating temperature of the step (1) is 30-150 ℃ and the heating time is 2-18 hours.
The feeding sequence of the step (3) is that the compound I-1, 4-dioxane and the compound 3 are added with the tetraphenylphosphine palladium or the bis (triphenylphosphine) palladium dichloride or the palladium acetate and the potassium hydroxide aqueous solution. The feeding ratio of the compound I-1 to the compound 3 to the tetraphenylphosphine palladium is 1:1-10:0.01-1.
The aqueous potassium hydroxide solution is adjusted to pH 7-8 to slightly alkaline, and the reaction requires an alkaline environment, and the alkali and the arylboronic acid generate tetravalent borate intermediate species.
The heating temperature of the step (3) is 30-120 ℃ and the heating time is 0.5-24 hours.
The invention has the following beneficial effects:
(1) The compound is an ideal photosensitizer and can be used for one-step tumor research of B16 cells.
(2) The synthesis method and the application preparation method of the photosensitizer are simple, have strong penetrability and can be used for photodynamic therapy.
(3) The synthesis reaction conditions of the invention employ a novel catalyst, wherein the catalyst can be tetraphenylphosphine palladium or bis (triphenylphosphine) palladium dichloride or palladium acetate.
Drawings
FIG. 1 is a spectrum of the compound I-1 obtained in example 1.
FIG. 2 is a spectrum of the compound I-2 obtained in example 1.
FIG. 3 is a spectrum of Compound I-3 obtained in example 11.
FIG. 4 is a graph showing cell viability of the compounds I-1, I-2, and I-3 obtained in examples 12 to 18.
Detailed Description
The present invention will be further illustrated by the following examples, but the scope of the invention is not limited to the examples.
Example 1
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were sequentially added, the mixture was stirred at 90℃for 8 hours and heated to complete the reaction, the reaction was distilled off, and after column chromatography purification, orange solid I-1 (165.7 mg) was obtained in 35.4% yield. Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol), tetrakis triphenylphosphine palladium (2.43 mg,0.0021 mmol) and potassium hydroxide aqueous solution (23.5 mg,0.42mmol, 210 μl of deionized water) were added sequentially, and the reaction was stirred for 8 hours at 60 ℃ for completion of the reaction, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-2 (50.3 mg) in 37.8% yield.
Example 2
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (344 mg,2 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were sequentially added, the mixture was stirred at 90℃for 8 hours and heated to complete the reaction, the reaction was distilled off, and after column chromatography purification, orange solid I-1 (270.0 mg) was obtained in 57.7% yield. When the amount of 4-bromopyrrole-2-carbaldehyde was increased 1-fold relative to example 1, the yield was increased by 22.3%. Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (121.4 mg,0.42 mmol) and tetrakis triphenylphosphine palladium (2.43 mg,0.0021 mmol) were sequentially added, and an aqueous potassium hydroxide solution (23.5 mg,0.42mmol, 210 μl of deionized water) was heated at 60 ℃ and stirred for 8 hours to react completely, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-2 (78.7 mg) in 59.1% yield. When the amount of 4-diphenylaminophenylboronic acid was increased 1-fold relative to example 1, the yield was increased by 21.3%.
Example 3
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.18 mL,2 mmol) and acetic acid (0.12 mL,2 mmol) were sequentially added, the mixture was stirred at 90℃for 8 hours and heated to complete the reaction, the reaction was distilled off soon, and after column chromatography purification, orange solid I-1 (178.3 mg) was obtained in 38.1% yield. When the amount of piperidine, acetic acid was increased 1-fold relative to example 1, the yield was not significantly changed. Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol), tetrakis triphenylphosphine palladium (2.43 mg,0.0021 mmol) and potassium hydroxide aqueous solution (23.5 mg,0.42mmol, 210 μl of deionized water) were added sequentially, and the reaction was stirred for 6 hours at 90 ℃ for complete reaction, and the reactant was washed with water, dried and purified by column chromatography to give orange solid I-2 (85.5 mg) in 64.2% yield. When the reaction temperature was increased by 30℃relative to example 1, the reaction time was reduced by 2 hours, and the yield was increased by 26.4%.
Example 4
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were sequentially added, the mixture was stirred at 120℃for 6 hours and heated to complete the reaction, the reaction was distilled off, and after column chromatography purification, orange solid I-1 (303.7 mg) was obtained in 64.9% yield. When the reaction temperature was increased by 30℃relative to example 1, the reaction time was reduced by 2 hours, and the yield was increased by 29.5%. Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol), tetrakis triphenylphosphine palladium (4.86 mg,0.0042 mmol) and potassium hydroxide aqueous solution (23.5 mg,0.42mmol, 210 μl of deionized water) were added sequentially, and the reaction was stirred for 8 hours at 60 ℃ for completion of the reaction, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-2 (60.0 mg) in 45.1% yield. When the amount of the tetrakis triphenylphosphine palladium was increased 1-fold relative to example 1, the yield was increased by 7.3%.
Example 5
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were sequentially added, the mixture was stirred at 140℃for 6 hours and heated to complete the reaction, the reaction was distilled off, and after column chromatography purification, orange solid I-1 (131 mg) was obtained in 28.0% yield. When the reaction temperature was increased by 30℃relative to example 1, the reaction time was reduced by 2 hours, and the yield was reduced by 7.4%. Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol), tetrakis triphenylphosphine palladium (2.43 mg,0.0021 mmol) and potassium hydroxide aqueous solution (47.0 mg,0.84mmol, 210 μl of deionized water) were added sequentially, and the reaction was stirred for 8 hours at 60 ℃ for completion of the reaction, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-2 (30.0 mg) in 22.5% yield. When the amount of potassium hydroxide was increased 1-fold relative to example 1, i.e., the concentration of the aqueous potassium hydroxide solution was increased 1-fold relative to example 1, the yield was reduced by 15.3%.
Example 6
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were sequentially added, the mixture was stirred at 60℃for 12 hours and heated to complete the reaction, the reaction was distilled off, and after column chromatography purification, orange solid I-1 (105.8 mg) was obtained in 22.6% yield. When the reaction temperature was lowered by 30℃relative to example 1, the reaction time was increased by 4 hours, and the yield was lowered by 12.8%. Compound I-1 (100 mg,0.21 mmol) was weighed, 12ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol), tetrakis triphenylphosphine palladium (2.43 mg,0.0021 mmol) and potassium hydroxide aqueous solution (23.5 mg,0.42mmol, 210 μl of deionized water) were added sequentially, and the reaction was stirred for 8 hours at 60 ℃ for completion of the reaction, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-2 (45.8 mg) in 34.4% yield. When the amount of 1, 4-dioxane was increased 1-fold relative to example 1, the yield was not significantly changed.
Example 7
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 60.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were sequentially added, the mixture was stirred at 90℃for 8 hours and heated to complete the reaction, the reaction was distilled off, and after column chromatography purification, orange solid I-1 (157.7 mg) was obtained in 33.7% yield. When the amount of toluene was doubled relative to example 1, the yield was not significantly changed. Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol), tetrakis triphenylphosphine palladium (2.43 mg,0.0021 mmol) and potassium hydroxide aqueous solution (23.50 mg,0.42mmol, 210 μl of deionized water) were added sequentially, and the reaction was stirred at 30 ℃ for 16 hours to complete the reaction, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-2 (15.8 mg) in 11.9% yield. When the reaction temperature was lowered by 30℃relative to example 1, the reaction time was increased by 8 hours, and the yield was lowered by 25.9%.
Example 8
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were sequentially added, the mixture was stirred at 90℃for 8 hours and heated to complete the reaction, the reaction was distilled off, and after purification by column chromatography, orange solid I-1 (174.1 mg) was obtained in 37.2% yield. Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol), tetrakis triphenylphosphine palladium (2.43 mg,0.0021 mmol) and potassium hydroxide aqueous solution (23.5 mg,0.42mmol, 210 μl of deionized water) were added sequentially, and the reaction was stirred for 8 hours at 60 ℃ for completion of the reaction, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-2 (50.3 mg) in 37.8% yield.
Example 9
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, piperidine (0.09 mL,1 mmol), acetic acid (0.06 mL,1 mmol) were added sequentially, finally 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol) was added, the reaction was stirred at 90℃for 8 hours and completed, the reaction was distilled off soon, and after purification by column chromatography, orange solid I-1 (58.5 mg) was obtained in 12.5% yield. When the piperidine, acetic acid addition sequence was changed to precede 4-bromopyrrole-2-carbaldehyde with respect to example 1, the yield was reduced by 22.9%. . Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol) was added sequentially, bis (triphenylphosphine) palladium dichloride (1.47 mg,0.0021 mmol), aqueous potassium hydroxide solution (23.5 mg,0.42mmol, deionized water 210 μl) was heated at 60 ℃ and stirred for 8 hours to react completely, the reaction was washed with water, dried, and purified by column chromatography to give orange solid I-2 (19.3 mg) in 14.5% yield. When the catalyst was changed from tetrakis triphenylphosphine palladium to bis (triphenylphosphine) palladium dichloride, the yield was reduced by 23.3%.
Example 10
The compound 1, 2, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00 mM LDMF was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were added sequentially, the mixture was stirred at 90℃for 8 hours and heated to complete the reaction, the reaction was distilled off, and after column chromatography purification, orange solid I-1 (107.2 mg) was obtained in 22.9% yield. When the solvent was changed from toluene to DMF, the yield was reduced by 12.5%. Compound I-1 (100 mg,0.21 mmol) was weighed, 6ml of 1, 4-dioxane was mixed and dissolved, then 4-diphenylaminophenylboronic acid (60.7 mg,0.21 mmol), palladium acetate (0.47 mg,0.0021 mmol) and aqueous potassium hydroxide solution (23.5 mg,0.42mmol, 210 μl of deionized water) were sequentially added, and the mixture was heated at 60 ℃ for 8 hours to complete the reaction, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-2 (6.9 mg) in 5.2% yield. When the catalyst was changed from palladium tetraphenylphosphine to palladium acetate, the yield was lowered by 32.6%.
Example 11
The compound 1, 3-trimethylindole (1599 mg,1 mmol) was weighed, 30.00mL of toluene was mixed and dissolved, then 4-bromopyrrole-2-carbaldehyde (172 mg,1 mmol), piperidine (0.09 mL,1 mmol) and acetic acid (0.06 mL,1 mmol) were sequentially added, the mixture was stirred at 90℃for 8 hours and heated to complete the reaction, the reaction was distilled off, and after column chromatography purification, orange solid I-1 (173.6 mg) was obtained in 37.1% yield. Compound I-1 (100 mg,0.21 mmol) was weighed, 6mL of 1, 4-dioxane was mixed and dissolved, then 4-cyanobenzeneboronic acid (27.5 mg,0.21 mmol), tetrakis triphenylphosphine palladium (2.43 mg,0.0021 mmol) and potassium hydroxide aqueous solution (23.5 mg,0.42mmol, 210. Mu.L of deionized water) were added sequentially, and the reaction was stirred at 60℃for 8 hours to complete the reaction, and the reaction was washed with water, dried and purified by column chromatography to give orange solid I-3 (43.9 mg) in 33.0% yield.
EXAMPLE 12 efficiency of singlet oxygen production by Compound I-1
Compound I-1 (4.69 mg,0.01 mmol) was weighed, 1mL of DCM was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 10. Mu.L of the mother liquor was taken and dissolved in 3mL of DCM to prepare a solution to be tested of 0.01. Mu.mol/L. Weighing DPBF (2.70 mg,0.01 mmol) as a compound and 1mL of ethanol as a reaction productDissolving to prepare 0.01mol/L mother solution, and then dissolving 20 mu L mother solution into a solution to be tested containing the compound I-1. Under irradiation of 416nm light source, DPBF (1, 3-diphenylisobenzofuran) 1 O 2- The specific capture reagent calculates the singlet oxygen production efficiency and selects 8-phenyl-1, 3,5, 7-tetramethyl-2, 6-bromo-BODIPY (2 Br-BDP) as reference (ΦΔ=0.31 in DCM). After irradiation with laser light, the maximum absorption band of DPBF at 415nm decreased, and the cell viability after irradiation decreased from 100% to 38%, indicating the generation of singlet oxygen. The absorbance of DPBF gradually decreases with irradiation time. According to the degradation condition of DPBF, the singlet oxygen generation efficiency of I-1 is calculated to be 0.57.
EXAMPLE 13 efficiency of singlet oxygen production by Compound I-1
Compound I-1 (4.69 mg,0.01 mmol) was weighed, 1mL of DCM was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 20. Mu.L of the mother liquor was taken and dissolved in 3mL of DCM to prepare a solution to be tested of 0.02. Mu.mol/L. Compound DPBF (2.70 mg,0.01 mmol) was weighed, 1mL of ethanol was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 20 μl of the mother liquor was taken and dissolved into a solution to be measured containing compound I-1. Under irradiation of 416nm light source, DPBF (1, 3-diphenylisobenzofuran) 1 O 2- The specific capture reagent calculates the singlet oxygen production efficiency and selects 8-phenyl-1, 3,5, 7-tetramethyl-2, 6-bromo-BODIPY (2 Br-BDP) as reference (ΦΔ=0.31 in DCM). After irradiation with laser light, the maximum absorption band of DPBF at 415nm decreased, and the cell viability after irradiation decreased from 100% to 25%, indicating the generation of singlet oxygen. The absorbance of DPBF gradually decreases with irradiation time. According to the degradation condition of DPBF, the singlet oxygen generation efficiency of I-1 is calculated to be 0.77.
EXAMPLE 14 Compound I-1 singlet oxygen production efficiency
Compound I-1 (4.69 mg,0.01 mmol) was weighed, 1mL of DCM was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 10. Mu.L of the mother liquor was taken and dissolved in 3mL of DCM to prepare a solution to be tested of 0.01. Mu.mol/L. Compound DPBF (2.70 mg,0.01 mmol) was weighed, 1mL of acetonitrile was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 20 μl of the mother liquor was taken and dissolved into a solution to be measured containing compound I-1. Under the irradiation of 416nm light source, DPBF (1, 3-diphenyl)Isobenzofurans) of the group 1 O 2- The specific capture reagent calculates the singlet oxygen production efficiency and selects 8-phenyl-1, 3,5, 7-tetramethyl-2, 6-bromo-BODIPY (2 Br-BDP) as reference (ΦΔ=0.31 in DCM). After irradiation with laser light, the maximum absorption band of DPBF at 415nm decreased, and the cell viability after irradiation decreased from 100% to 46%, indicating the generation of singlet oxygen. The absorbance of DPBF gradually decreases with irradiation time. According to the degradation condition of DPBF, the singlet oxygen generation efficiency of I-1 is calculated to be 0.51.
EXAMPLE 15 efficiency of singlet oxygen production by Compound I-1
Compound I-1 (4.69 mg,0.01 mmol) was weighed, 1mL of DCM was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 10. Mu.L of the mother liquor was taken and dissolved in 3mL of DCM to prepare a solution to be tested of 0.01. Mu.mol/L. Compound DPBF (2.70 mg,0.01 mmol) was weighed, 1mL of methanol was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 20 μl of the mother liquor was taken and dissolved into a solution to be measured containing compound I-1. Under irradiation of 416nm light source, DPBF (1, 3-diphenylisobenzofuran) 1 O 2- The specific capture reagent calculates the singlet oxygen production efficiency and selects 8-phenyl-1, 3,5, 7-tetramethyl-2, 6-bromo-BODIPY (2 Br-BDP) as reference (ΦΔ=0.31 in DCM). After irradiation with laser light, the maximum absorption band of DPBF at 415nm decreased, and the cell viability after irradiation decreased from 100% to 42%, indicating the generation of singlet oxygen. The absorbance of DPBF gradually decreases with irradiation time. According to the degradation condition of DPBF, the singlet oxygen generation efficiency of I-1 is calculated to be 0.57.
EXAMPLE 16 Compound I-1 singlet oxygen production efficiency
Compound I-1 (4.69 mg,0.01 mmol) was weighed, 1mL of DCM was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 10. Mu.L of the mother liquor was taken and dissolved in 3mL of DCM to prepare a solution to be tested of 0.01. Mu.mol/L. Compound DPBF (2.70 mg,0.01 mmol) was weighed, 1mL of ethanol was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 20 μl of the mother liquor was taken and dissolved into a solution to be measured containing compound I-1. Under irradiation of 450nm light source, DPBF (1, 3-diphenyl isobenzofuran) 1 O 2- The specific capture agent calculates the singlet oxygen production efficiency and selects 8-phenyl-1, 3,5, 7-tetramethyl-2, 6-bromoBODIPY (2 Br-BDP) as reference (ΦΔ=0.31 in DCM). After irradiation with laser light, the maximum absorption band of DPBF at 415nm decreased, and the cell viability after irradiation decreased from 100% to 58%, indicating the generation of singlet oxygen. The absorbance of DPBF gradually decreases with irradiation time. According to the degradation condition of DPBF, the singlet oxygen generation efficiency of I-1 is calculated to be 0.44.
EXAMPLE 17 efficiency of singlet oxygen production by Compound I-2
Compound I-2 (6.34 mg,0.01 mmol) was weighed, 1mL of DCM was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 10. Mu.L of the mother liquor was taken and dissolved in 3mL of DCM to prepare a solution to be tested of 0.01. Mu.mol/L. Compound DPBF (2.70 mg,0.01 mmol) was weighed, 1mL of ethanol was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 20 μl of the mother liquor was taken and dissolved into a solution to be measured containing compound I-2. Under irradiation of 412nm light source, DPBF (1, 3-diphenyl isobenzofuran) 1 O 2- The specific capture reagent calculates the singlet oxygen production efficiency and selects 8-phenyl-1, 3,5, 7-tetramethyl-2, 6-bromo-BODIPY (2 Br-BDP) as reference (ΦΔ=0.31 in DCM). After irradiation with laser light, the maximum absorption band of DPBF at 415nm decreased, and the cell viability after irradiation decreased from 100% to 60%, indicating the generation of singlet oxygen. The absorbance of DPBF gradually decreases with irradiation time. According to the degradation condition of DPBF, the singlet oxygen generation efficiency of I-2 is calculated to be 0.43.
EXAMPLE 18 efficiency of singlet oxygen production by Compound I-1
Compound I-3 (4.92 mg,0.01 mmol) was weighed, 1mL of DCM was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 10. Mu.L of the mother liquor was taken and dissolved in 3mL of DCM to prepare a solution to be tested of 0.01. Mu.mol/L. Compound DPBF (2.70 mg,0.01 mmol) was weighed, 1mL of ethanol was taken and dissolved to prepare a mother liquor of 0.01mol/L, and then 20 μl of the mother liquor was taken and dissolved into a solution to be measured containing compound I-3. Under irradiation of 436nm light source, DPBF (1, 3-diphenyl isobenzofuran) 1 O 2- The specific capture reagent calculates the singlet oxygen production efficiency and selects 8-phenyl-1, 3,5, 7-tetramethyl-2, 6-bromo-BODIPY (2 Br-BDP) as reference (ΦΔ=0.31 in DCM). After irradiation with laser light, the maximum absorption band of DPBF at 415nm is reduced, and the cell viability after irradiation is changed from 1The 00% drop to 74% indicates singlet oxygen production. The absorbance of DPBF gradually decreases with irradiation time. According to the degradation condition of DPBF, the singlet oxygen generation efficiency of I-3 is calculated to be 0.35.

Claims (9)

1. The novel photosensitizer is characterized in that the chemical structural formula of the compound is as follows:
wherein the substituent R is any one selected from bromine, N-dimethylaminophenyl and p-cyanophenyl.
2. A method of synthesizing a novel photosensitizer according to claim 1, characterized in that the method comprises the following synthetic routes:
wherein, the substituent R is any one selected from bromine, N-dimethylaminophenyl and p-cyanophenyl;
(1) Adding a compound 1, toluene or DMF into a reaction bottle at room temperature, stirring for dissolution, adding a compound 2, piperidine and acetic acid, and heating for reflux to obtain a reaction solution;
(2) Spin-steaming the reaction liquid in the step (1), and separating by silica gel column chromatography to obtain a product I-1;
(3) Respectively adding 1, 4-dioxane and 3 into the compound I-1 in the step (2), stirring for dissolving, adding a catalyst, adjusting the pH value with a potassium hydroxide aqueous solution, and heating to obtain a reaction solution;
(4) And (3) respectively washing, extracting, drying, concentrating and purifying the reaction liquid in the step (3) to obtain a product I, namely the novel photosensitizer.
3. The method according to claim 2, wherein in the step (1), the feed ratio of the compound 1, the compound 2, the piperidine and the acetic acid is 1:1-10:1-10:1-10.
4. The method according to claim 2, wherein the step (1) is carried out in the order of compound 1, toluene or DMF, compound 2, piperidine, acetic acid.
5. The method according to claim 2, wherein the heating reflux reaction temperature in the step (1) is 30 to 150 ℃ and the heating time is 2 to 18 hours.
6. The process according to claim 2, wherein the catalyst in step (2) is selected from the group consisting of tetrakis triphenylphosphine palladium or bis (triphenylphosphine) palladium dichloride or palladium acetate.
7. The process according to claim 2, wherein the feed ratio of compound I-1 to compound 3 in step (3) is 1:1-100.
8. The method according to claim 2, wherein the heating reaction temperature in the step (3) is 30-120 ℃ and the reaction time is 0.5-24h.
9. Use of a novel photosensitizer in photodynamic therapy as claimed in claim 1.
CN202310634668.0A 2023-05-31 2023-05-31 Synthesis method and application of novel photosensitizer Pending CN116789676A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118184663A (en) * 2024-03-06 2024-06-14 湖北宜美特全息科技有限公司 Nitrogen-containing heterocyclic compound, and preparation method and application thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118184663A (en) * 2024-03-06 2024-06-14 湖北宜美特全息科技有限公司 Nitrogen-containing heterocyclic compound, and preparation method and application thereof

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