Search

CN-121717729-B - Preparation method and application of I-type compound photosensitizer with hydrogen sulfide detection performance

CN121717729BCN 121717729 BCN121717729 BCN 121717729BCN-121717729-B

Abstract

The application relates to the biomedical field, and discloses a preparation method and application of an I-type compound photosensitizer with hydrogen sulfide detection performance. The application synthesizes triphenylamine derivative TPAB with A-pi-D-pi-A conjugated structure by adopting TPA-CHO and MN as monomers and adopting Schiff base reaction, and further introduces Cu 2+ into TPAB molecules to form the stable metal complex compound photosensitizer through coordination bonds. The functional compound photosensitizer TPAB-Cu 2+ has the characteristics of mainly generating I-type ROS, has high-efficiency photodynamic bactericidal activity in an anoxic drug-resistant bacteria infection environment, can be applied to the hydrogen sulfide level detection of a drug-resistant bacteria infection microenvironment to realize the early warning of drug-resistant bacteria infection and the real-time detection of a treatment process, and solves the technical problems of strong photosensitizer oxygen dependence and insufficient response sensitivity and specificity of the drug-resistant bacteria infection microenvironment in the existing photodynamic therapy.

Inventors

  • ZHANG JUNYAN
  • CHEN XIN
  • Li Qianquan
  • WU JUN
  • Suo Jinshan
  • Sheng Ruanmei

Assignees

  • 上海市松江区中心医院（上海交通大学附属第一人民医院松江分院）

Dates

Publication Date
20260508
Application Date
20260214

Claims (10)

  1. 1. The preparation method of the I-type compound photosensitizer TPAB-Cu 2+ with hydrogen sulfide detection performance is characterized by comprising the following steps: step 1, dissolving N, N-bis (4-formylphenyl) aniline and 4-aminophenyl hydrazine in a solvent, refluxing under an inert atmosphere, filtering, recrystallizing to obtain triphenylamine derivative TPAB powder, wherein the structure of TPAB is as follows: ; Step2, dissolving the triphenylamine derivative TPAB obtained in the step1 in a solvent, then adding Cu (NO 3 ) 2 , stirring at room temperature, drying, purifying and drying to obtain a compound photosensitizer TPAB-Cu 2+ , wherein the structure of TPAB-Cu 2+ is as follows: 。
  2. 2. The process according to claim 1, wherein the process for preparing N, N-bis (4-formylphenyl) aniline comprises dissolving triphenylamine in DMF solvent, adding POCl 3 dropwise at 0deg.C, stirring at room temperature until the color turns red, heating to react, cooling, neutralizing, filtering, drying, and purifying to obtain N, N-bis (4-formylphenyl) aniline powder.
  3. 3. The method according to claim 2, wherein the ratio of triphenylamine to POCl 3 in the method for producing N, N-bis (4-formylphenyl) aniline is 20 mmol:102.0 mmol.
  4. 4. The preparation method of the 4-amino phenylhydrazine according to claim 1, wherein the preparation method comprises the steps of adding methyl 4-amino benzoate into a hydrazine hydrate solution, refluxing under an inert atmosphere, adding ethanol and stirring, cooling, filtering, recrystallizing and drying in vacuum after the reaction is completed, so as to obtain the 4-amino phenylhydrazine crystal.
  5. 5. The method according to claim 4, wherein the ratio of the amount of the solution of methyl 4-aminobenzoate and the amount of the solution of hydrazine hydrate is 6.0 g/30.0 mL.
  6. 6. The method according to claim 1, wherein the ratio of the N, N-bis (4-formylphenyl) aniline to 4-aminophenylhydrazine used in the step 1 is 1.0 mmol:2.0 mmol.
  7. 7. The preparation method according to claim 6, wherein the specific step of the step 1 is to dissolve N, N-bis (4-formylphenyl) aniline and 4-aminophenylhydrazine in ethanol, reflux the solution at 80 ℃ for 8 hours under nitrogen atmosphere, filter the precipitate, and recrystallize the precipitate with absolute ethanol to obtain triphenylamine derivative TPAB powder.
  8. 8. The method according to claim 1, wherein in the step 2, the molar ratio of triphenylamine derivative TPAB to Cu (NO 3 ) 2 ) is 1 (1-3).
  9. 9. The preparation method according to claim 8, wherein the specific step of the step 2 is that the triphenylamine derivative TPAB obtained in the step 1 is dissolved in ethanol, then Cu (NO 3 ) 2 powder is added, stirring is carried out for 24 hours at room temperature, rotary evaporation drying is carried out, the obtained product is dissolved in CHCl 2 , then the three times of extraction is carried out by using CHCl 2 and water in a volume ratio of 1:1, the purified solution is dried by rotary evaporation, and further drying is carried out under vacuum, thus obtaining the compound photosensitizer TPAB-Cu 2+ .
  10. 10. Use of the compound photosensitizer TPAB-Cu 2+ prepared by the preparation method of any one of claims 1-9 in the preparation of a product for type I photodynamic sterilization in a resistant bacteria infection microenvironment and/or for detecting hydrogen sulfide levels in an infection microenvironment.

Description

Preparation method and application of I-type compound photosensitizer with hydrogen sulfide detection performance Technical Field The application relates to the biomedical field, in particular to a preparation method and application of an I-type compound photosensitizer with hydrogen sulfide detection performance. Background The skin serves as the largest protective barrier for the human body and plays a key role in maintaining life safety. But skin is extremely susceptible to physical damage and bacterial infection due to prolonged exposure to complex external environments. To promote healing of infected wounds, antibiotics are often used to kill bacteria. However, overuse and abuse of antibiotics has led to the emergence of multi-drug resistant (MDR) bacteria, such as methicillin-resistant staphylococcus aureus (MRSA). These MDR bacteria have evolved a variety of antibiotic resistance mechanisms, and more importantly, the formation of bacterial biofilms constitutes a physical and biochemical barrier, significantly impeding antibiotic diffusion, further exacerbating antibiotic resistance. Due to the lack of effective drugs, MDR bacterial infection can hinder wound healing and is susceptible to rapid deterioration, leading to serious complications such as shock, sepsis and pneumonia, constituting a significant health risk. Recent studies have shown that novel nanomedicines (e.g., silver nanoparticles and metal oxide nanoparticles) can effectively kill MDR bacteria. However, concerns remain regarding the potential biotoxicity and long-term retention of these materials. Photodynamic therapy (PDT) based on small organic molecule photosensitizers provides a promising therapeutic strategy for the treatment of wounds infected by MDR bacteria, with advantages including biosafety, non-invasiveness and time-space selectivity. During conventional PDT, photosensitizers convert ambient oxygen molecules into Reactive Oxygen Species (ROS) under light, directly killing bacteria by oxidizing MDR bacteria's lipids, proteins and DNA. Photosensitizers are classified into type I and type II photosensitizers, the type I photosensitizers generate ROS (O 2- ·and·oh) mainly through electron transfer or hydrogen extraction processes, and the type II photosensitizers convert oxygen in a ground state into singlet oxygen mainly through energy transfer processes (1O2). Recent studies have also shown that photosensitizers can possess microenvironment response characteristics through precise molecular design, enabling non-invasive monitoring of treatment progression. However, despite the significant advantages of PDT for the treatment of MDR bacterial wound infections, several challenges remain to be resolved. On the one hand, most of the existing small molecule photosensitizers have oxygen dependence (type II photosensitizers), and the infected microenvironment is usually in an anoxic state, and furthermore, the formation of biofilms can further aggravate the anoxic state, which can significantly reduce the therapeutic effect of the oxygen-dependent photosensitizers. On the other hand, the synthesis of small molecule photosensitizers with both high selectivity and high sensitivity remains an important challenge due to the complexity of the infectious microenvironment, and synthesis of microenvironment-responsive photosensitizers often requires complex and harsh reaction conditions. Therefore, there is a need to develop a functional photosensitizer that overcomes the limitation of low-oxygen environments and enables accurate monitoring of key biomarkers in an infected microenvironment using innovative and simple and efficient synthetic strategies. Disclosure of Invention The application aims to provide a preparation method of a compound photosensitizer TPAB-Cu 2+ and application of the compound photosensitizer in detecting hydrogen sulfide levels in a wound infection microenvironment, so as to solve the problems of strong photosensitizer oxygen dependence, insufficient microenvironment response specificity and sensitivity and complex and harsh molecular synthesis process in the existing photodynamic therapy. In order to achieve the above object, the present application adopts the following technical scheme: In a first aspect, the present application provides a type I compound photosensitizer TPAB-Cu 2+ having hydrogen sulfide detection properties, comprising the steps of: step 1, dissolving TPA-CHO and MN in a solvent, refluxing in an inert atmosphere, filtering, and recrystallizing to obtain TPAB powder; And 2, dissolving TPAB obtained in the step 1 in a solvent, then adding Cu (NO 3)2, stirring at room temperature, drying, purifying and drying to obtain the compound photosensitizer TPAB-Cu 2+. Further, the preparation method of the TPA-CHO comprises the steps of dissolving triphenylamine in a solvent, dropwise adding POCl 3 at 0 ℃, stirring at room temperature until the color turns red, heating for reaction, cooling, neutralizing, filt