CN112480377B - 一种以精氨酸为侧链的共轭聚合物的制备方法及其应用 - Google Patents

一种以精氨酸为侧链的共轭聚合物的制备方法及其应用 Download PDF

Info

Publication number
CN112480377B
CN112480377B CN202011392834.3A CN202011392834A CN112480377B CN 112480377 B CN112480377 B CN 112480377B CN 202011392834 A CN202011392834 A CN 202011392834A CN 112480377 B CN112480377 B CN 112480377B
Authority
CN
China
Prior art keywords
arginine
conjugated polymer
compound
fluorene
carbonyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202011392834.3A
Other languages
English (en)
Other versions
CN112480377A (zh
Inventor
冯丽恒
李瑞鹏
赵晓瑜
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanxi University
Original Assignee
Shanxi University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanxi University filed Critical Shanxi University
Priority to CN202011392834.3A priority Critical patent/CN112480377B/zh
Publication of CN112480377A publication Critical patent/CN112480377A/zh
Application granted granted Critical
Publication of CN112480377B publication Critical patent/CN112480377B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G61/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G61/12—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule
    • C08G61/122—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides
    • C08G61/123—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides derived from five-membered heterocyclic compounds
    • C08G61/126—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides derived from five-membered heterocyclic compounds with a five-membered ring containing one sulfur atom in the ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G61/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G61/12—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule
    • C08G61/122—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides
    • C08G61/123—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides derived from five-membered heterocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/10—Definition of the polymer structure
    • C08G2261/12—Copolymers
    • C08G2261/124—Copolymers alternating
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/10—Definition of the polymer structure
    • C08G2261/14—Side-groups
    • C08G2261/143—Side-chains containing nitrogen
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/10—Definition of the polymer structure
    • C08G2261/18—Definition of the polymer structure conjugated
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/30—Monomer units or repeat units incorporating structural elements in the main chain
    • C08G2261/31—Monomer units or repeat units incorporating structural elements in the main chain incorporating aromatic structural elements in the main chain
    • C08G2261/314—Condensed aromatic systems, e.g. perylene, anthracene or pyrene
    • C08G2261/3142—Condensed aromatic systems, e.g. perylene, anthracene or pyrene fluorene-based, e.g. fluorene, indenofluorene, or spirobifluorene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/30—Monomer units or repeat units incorporating structural elements in the main chain
    • C08G2261/32—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain
    • C08G2261/322—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain non-condensed
    • C08G2261/3223—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain non-condensed containing one or more sulfur atoms as the only heteroatom, e.g. thiophene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/30—Monomer units or repeat units incorporating structural elements in the main chain
    • C08G2261/32—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain
    • C08G2261/324—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain condensed
    • C08G2261/3246—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain condensed containing nitrogen and sulfur as heteroatoms

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明提供了一种以精氨酸为侧链的共轭聚合物的制备方法及其应用。该聚合物以Fmoc‑L‑精氨酸为原料，经溴取代反应得到化合物((2,7‑二溴‑9H‑芴‑9‑甲氧基)羰基)‑L‑精氨酸；将化合物((2,7‑二溴‑9H‑芴‑9‑甲氧基)羰基)‑L‑精氨酸和化合物4,7‑二(5‑三甲基锡噻吩基‑2‑)2,1,3‑苯并噻二唑经stille偶联反应得到聚合物聚((2‑(5‑(7‑(噻吩‑2‑基)苯并[c][1,2,5]噻二唑‑4‑基)噻吩‑2‑基)‑9H‑芴‑9‑甲氧基)羰基)‑L‑精氨酸(PFLB)。该聚合物具有优异的活性氧和活性氮产生能力，可高效杀伤革兰氏阳性菌。其制备方法操作简单，反应条件温和，在抗菌治疗方面有较高的应用价值。

Description

一种以精氨酸为侧链的共轭聚合物的制备方法及其应用
技术领域
本发明属于生物医药领域，具体涉及一种以精氨酸为侧链的共轭聚合物的制备方法及其应用。
背景技术
细菌感染是困扰人类的一类高发性疾病，细菌病原体对人类健康构成重大威胁。金黄色葡萄球菌是一种高度多功能机会致病菌，其致病机制多样，发病机理复杂，其广泛的分布在自然界和人体皮肤及各个与外界相通的体腔，为最常见的化脓菌之一，也是导致医院内感染的主要病原菌之一，常引起局部化脓感染，也可引起肺炎、伪膜性肠炎、心包炎等，甚至败血症、脓毒症等全身感染。近年来，美国疾病控制中心报告，由金黄色葡萄球菌引起的感染占第二位，仅次于大肠杆菌，是目前最难以对付的病菌之一。金黄色葡萄球菌尽管本领域已知的方法是应用抗生素进行治疗，但是由于人类滥用抗生素，导致耐药性菌株不断出现，从而使抗生素的治疗效果迅速下降。随着耐药菌的广泛出现，细菌耐药问题日益严重。另一方面，抗生素的研发周期长、难度大、前期投入高，而且合成的药物毒副作用强，传统的抗生素已经不能满足人们的需要，人们亟需一种新型的抑菌治疗方法。光动力抗菌疗法是基于光动力反应的抗菌方法，由光敏剂、光、氧分子三者相互作用后，通过光动力反应产生活性氧(ROS)，作用于病原菌的不同分子结构(如脂质、蛋白质、酶和DNA)，对病原菌造成不可逆性损害，从而达到灭菌目的的治疗方法。因此，合成一种高效光动力抗菌的聚合物是本发明的宗旨。
发明内容
本发明的目的是提供一种以精氨酸为侧链的共轭聚合物，其对革兰氏阳性菌具有高效光动力杀伤，该光敏剂具有近红外光发射，同时具有优异的活性氧和活性氮产生能力，是一类潜在的应用于病原菌杀伤的有机光敏试剂。本发明的有机光敏剂所采用的制备方法操作简单，条件温和，在抗菌治疗方面有较高的应用价值。
为达到上述目的，本发明采用了以下技术方案：
一种以精氨酸为侧链的共轭聚合物，其结构式为：
Figure BDA0002811483310000021
一种以精氨酸为侧链的共轭聚合物的制备方法，具体包括以下步骤：
步骤1：将Fmoc-L-精氨酸、铁粉与液溴混合，再加入氯仿和乙酸，避光室温反应；反应完成后，经柱色谱分离得白色固体，即化合物((2,7-二溴-9H-芴-9-甲氧基)羰基)-L-精氨酸；
步骤2：在氮气气体保护下，将化合物((2,7-二溴-9H-芴-9-甲氧基)羰基)-L-精氨酸、化合物4,7-二(5-三甲基锡噻吩基-2-)2,1,3-苯并噻二唑与四三苯基磷钯溶于DMF中，加热回流反应；反应完成后，经透析处理得深红色固体，即共轭聚合物PFLB。
进一步，所述步骤1中Fmoc-L-精氨酸、铁粉与液溴的摩尔比为1﹕0.05～0.1﹕2～5。
进一步，所述步骤1中避光室温反应的时间为8-16h。
进一步，所述步骤2中化合物((2,7-二溴-9H-芴-9-甲氧基)羰基)-L-精氨酸、化合物4,7-二(5-三甲基锡噻吩基-2-)2,1,3-苯并噻二唑与四三苯基磷钯的摩尔比为1﹕1﹕0.05～0.1。
进一步，所述步骤2中加热回流的反应温度为100-120℃，反应时间为40-56h。
一种以精氨酸为侧链的共轭聚合物在抗菌领域中的应用。
本发明提供的共轭聚合物溶解在DMSO中，用水稀释后再使用。
与现有技术相比，本发明具有以下有益效果：
本发明提供的共轭聚合物由Fmoc-L-精氨酸、噻吩、苯并噻二唑单元共聚而成，其较强的共轭效应使得其有极强的光响应能力，该聚合物具有近红外光发射，同时具有优异的活性氧、活性氮产生能力。当聚合物在细菌感染部位作用时，由于偏酸性的环境，精氨酸上的胍基会带正电荷，更有利于其与细菌的接触。在光照条件下，聚合物会产生活性氧，从而刺激精氨酸产生活性氮，达到对细菌高效杀伤的目的。因而该聚合物是一种潜在高效杀伤病原菌的抗菌剂。这种杀伤方式与抗生素相比，不容易诱导细菌耐药性，且开发周期相对于抗菌药物短，因而可以在临床抗菌治疗当中具有很大的潜在应用价值。
附图说明
图1为本发明抗菌剂PFLB在水中的紫外吸收光谱图。
图2为本发明抗菌剂PFLB在水中的荧光发射光谱图。
图3为本发明抗菌剂PFLB的活性氧产生能力研究图。
图4为本发明抗菌剂PFLB的活性氮产生能力研究图。
图5为本发明抗菌剂PFLB在不同浓度下对金黄色葡萄球菌的抗菌性能研究图。
具体实施方式
以下给出本发明的具体实施例，用来对本发明的构成进行进一步说明。
实施例1
一种以精氨酸为侧链的共轭聚合物(PFLB)的制备
1、在50mL的圆底烧瓶中加入Fmoc-L-精氨酸(500mg,1.26mmol)、铁粉(7mg,0.126mmol)、液溴(1000mg,6.3mmol)，之后再加入15mL氯仿和3mL乙酸，避光室温反应12h，反应完成后，加入30mL蒸馏水，用乙酸乙酯萃取3次，用无水硫酸钠干燥有机相，旋除溶剂，经柱色谱分离(甲醇/二氯甲烷＝1/7,v/v)，得白色固体((2,7-二溴-9H-芴-9-甲氧基)羰基)-L-精氨酸231mg，产率33.1％。1H NMR(600MHz,CD3OD)δ7.87(s,1H),7.83(s,1H),7.74(d,J＝7.9Hz,2H),7.57(d,J＝7.1Hz,2H),4.43(s,1H),4.40(s,1H),4.29(d,J＝5.9Hz,1H),4.17(d,J＝2.5Hz,1H),3.20(s,2H),1.92(d,J＝8.3Hz,2H),1.67(s,2H)；HRMS-ESIfor C21H22Br2N4O4(m/z)555.0060[M+H]+。
2、在50mL的圆底烧瓶中加入((2,7-二溴-9H-芴-9-甲氧基)羰基)-L-精氨酸(100mg,0.18mmol)，4,7-二(5-三甲基锡噻吩基-2-)2,1,3-苯并噻二唑(113mg,0.18mmol)，抽真空通氮气三次，加入10mL DMF，再加入四三苯基磷钯(20mg,0.018mmol)，110℃下回流反应48h。反应完全后，用丙酮进行透析，最终得聚合物PFLB 30mg。1H NMR(600MHz,(CD3)2SO)δ8.24–8.14(m,2H),8.04(s,1H),7.95(s,2H),7.79(d,J＝2.2Hz,2H),7.26(d,J＝47.9Hz,3H),7.10(s,3H),6.68(s,1H),6.57(s,1H),5.32(s,2H),4.24(dd,J＝17.8,7.9Hz,2H),3.09(d,J＝6.0Hz,2H),2.02–1.96(m,2H),1.47(dd,J＝14.0,4.8Hz,2H)；Mn＝5036,Mw＝7845,PDI＝1.56.
实施例2
聚合物(PFLB)的紫外吸收和荧光发射光谱测试
配制3.9mmolL-1的PFLB的DMSO溶液5mL，准确移取77.5μL，超声溶于922.5μL的水中，配成300μmol L-1的PFLB的溶液。稀释至15倍后，准确移取1.5mL浓度为20μmol L-1的PFLB的溶液至四通比色皿中，然后在HITACHI UH5300紫外吸收仪上测定。再准确移取2.00mL的浓度为20μmol L-1的PFLB的水溶液至比色皿中，然后在HITACHI F-4600荧光仪上测定，激发狭缝宽度为10.0nm，发射狭缝宽度为10.0nm。测试是在室温和外界大气压下进行。紫外吸收和荧光发射光谱测试结果分别见图1和图2。由图1可知：聚合物(PFLB)的最大吸收峰为500nm。由图2可知：当激发波长为500nm时，聚合物(PFLB)的荧光发射为683nm。
实施例3
聚合物(PFLB)产生活性氧能力测试
取50μL 10.0mM的2,7-二氯荧光素二乙酸盐(DCFH DA)乙醇溶液，加入450μL乙醇稀释，再加入2.0mL 0.01M NaOH水溶液后室温避光活化30min。活化后加入10mL1×PBS缓冲溶液，混合后的2,7-二氯二氢荧光素(DCFH)溶液最终浓度为40μM。在比色皿中加入990mL活化的DCFH(40μM)溶液和10μL聚合物(PFLB)(1mM)的水溶液，混合均匀后，将所得溶液在白光(1.0mW/cm2)下照射5min，每分钟记录激发波长为488nm的DCFH溶液在500-700nm的荧光发射光谱，空白组为未添加任何待测活化的DCFH溶液(40μM)，在相同光照处理后用同样的方法检测其荧光发射光谱。所得测试结果见图3，说明本发明聚合物可以产生活性氧。
实施例4
聚合物(PFLB)产生活性氮能力测试
取2μL 5.0mM的3-氨基,4-氨基甲基-2',7'-二荧光素-二乙酸酯(DAF-FM DA)的DMSO溶液，加入400μL 0.001M氢氧化钠水溶液后室温避光活化30min。活化后加入1600μL 1×PBS缓冲溶液，混合后的3-氨基,4-氨基甲基-2',7'-二荧光素(DAF-FM)溶液最终浓度为5.0μM。在比色皿中加入900μL活化的DAF-FM(5.0μM)溶液和100μL聚合物(PFLB)(0.1mM)的水溶液，混合均匀后，将所得溶液在白光(50mW/cm2)下照射60min，每5分钟记录激发波长为460nm的DAF-FM溶液在480-800nm的荧光发射光谱，空白组为未添加任何待测活化的DAF-FM溶液(5.0μM)，在相同光照处理后用同样的方法检测其荧光发射光谱。所得测试结果见图4，说明该发明聚合物可以产生活性氮。
实施例5
聚合物(PFLB)对金黄色葡萄球菌的杀菌效果测试：
1)金黄色葡萄球菌(ATCC6358)的培养：
超净台开紫外灯消毒20～30min，超净台表面用75％酒精擦净，将灭菌的50mL离心管、NB培养基、1×PBS以及金黄色葡萄球菌的菌液拿到超净台中。取出一支50mL离心管，吸取10mL NB液体培养基到50mL无菌离心管中，再加入20μL金黄色葡萄球菌的菌种，37℃下，180rpm震荡培养10小时左右。
2)对金黄色葡萄球菌的杀菌率测试：
在超净台中，将在NB液体培养基中培养10小时左右的金黄色葡萄球菌吸取2mL菌液进行离心(7100rpm,2min)对金黄色葡萄球菌进行沉淀，将沉淀的金黄色葡萄球菌用1×PBS洗涤后离心沉淀，重复两次后，弃去上清液，将菌液重新悬浮于1×PBS中，调OD600为1.0。取100μL菌液(OD600＝1.0)和一定量的抗菌剂PFLB(最终浓度分别为2.5μM、5.0μM、7.5μM、10.0μM)在1.5mL离心管中作用，用无菌1×PBS将体积补充到500μL，并在暗处37℃下孵育20min，光照组白光50mW/cm2照射20min。空白组不加药。孵育结束后，稀释3.5×104倍后吸取100μL菌液均匀涂布于90mm NB固体培养基，37℃培养16h后计数菌落形成单位。图5为聚合物(PFLB)对金黄色葡萄球菌的杀菌性能测试结果，由图5可知，聚合物(PFLB)能高效的杀伤金黄色葡萄球菌，杀菌率高达95％以上。
本发明不局限于上述实施方式，任何人应得知在本发明的启示下作出的与本发明具有相同或相近的技术方案，均落入本发明的保护范围之内。

Claims (7)

1.一种以精氨酸为侧链的共轭聚合物，其特征在于，结构式为：
Figure 450344DEST_PATH_IMAGE001
。
2.一种以精氨酸为侧链的共轭聚合物的制备方法，其特征在于，包括以下步骤：
步骤1：将Fmoc-L-精氨酸、铁粉与液溴混合，再加入氯仿和乙酸，避光室温反应；反应完成后，经柱色谱分离得白色固体，即化合物((2,7-二溴-9H-芴-9-甲氧基)羰基)-L-精氨酸；
步骤2：在氮气气体保护下，将化合物((2,7-二溴-9H-芴-9-甲氧基)羰基)-L-精氨酸、化合物4,7-二(5-三甲基锡噻吩基-2-)2,1,3-苯并噻二唑与四三苯基磷钯溶于DMF中，加热回流反应；反应完成后，经透析处理得深红色固体，即共轭聚合物PFLB。
3.如权利要求2所述的一种以精氨酸为侧链的共轭聚合物的制备方法，其特征在于，所述步骤1中Fmoc-L-精氨酸、铁粉与液溴的摩尔比为1﹕0.05~0.1﹕2~5。
4.如权利要求2所述的一种以精氨酸为侧链的共轭聚合物的制备方法，其特征在于，所述步骤1中避光室温反应的时间为8-16h。
5.如权利要求2所述的一种以精氨酸为侧链的共轭聚合物的制备方法，其特征在于，所述步骤2中化合物((2,7-二溴-9H-芴-9-甲氧基)羰基)-L-精氨酸、化合物4,7-二(5-三甲基锡噻吩基-2-)2,1,3-苯并噻二唑与四三苯基磷钯的摩尔比为1﹕1﹕0.05~0.1。
6.如权利要求2所述的一种以精氨酸为侧链的共轭聚合物的制备方法，其特征在于，所述步骤2中加热回流的反应温度为100-120℃，反应时间为40-56h。
7.一种如权利要求1所述的以精氨酸为侧链的共轭聚合物在制备抗菌剂中的应用。
CN202011392834.3A 2020-12-01 2020-12-01 一种以精氨酸为侧链的共轭聚合物的制备方法及其应用 Active CN112480377B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011392834.3A CN112480377B (zh) 2020-12-01 2020-12-01 一种以精氨酸为侧链的共轭聚合物的制备方法及其应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011392834.3A CN112480377B (zh) 2020-12-01 2020-12-01 一种以精氨酸为侧链的共轭聚合物的制备方法及其应用

Publications (2)

Publication Number Publication Date
CN112480377A CN112480377A (zh) 2021-03-12
CN112480377B true CN112480377B (zh) 2021-09-28

Family

ID=74938994

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011392834.3A Active CN112480377B (zh) 2020-12-01 2020-12-01 一种以精氨酸为侧链的共轭聚合物的制备方法及其应用

Country Status (1)

Country Link
CN (1) CN112480377B (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114870014B (zh) * 2022-05-18 2023-07-07 南京邮电大学 一种多功能抗肿瘤高分子药物及其制备方法和用途

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101519490A (zh) * 2009-04-02 2009-09-02 中国科学院长春应用化学研究所 含氨基酸或肽基团的水溶性聚合物及其制法和应用
EP2511290A1 (en) * 2011-04-15 2012-10-17 Centre National de la Recherche Scientifique Compounds binding to the bacterial beta ring
AU2012247051B2 (en) * 2002-09-06 2015-02-19 Cerulean Pharma Inc. Cyclodextrin-based polymers for therapeutics delivery
CN106083866A (zh) * 2016-07-07 2016-11-09 南京师范大学 一种精氨酸取代的酞菁衍生物及其合成方法和应用
CN108329460A (zh) * 2018-03-08 2018-07-27 山西大学 一种光动力杀菌聚合物及其制备方法和应用
CN110172156A (zh) * 2019-04-19 2019-08-27 华中科技大学 一种含有共轭聚合物的复合纳米粒子及其制备方法与应用
CN110408008A (zh) * 2019-07-04 2019-11-05 南京工业大学 具有空穴传输性能的带有氨基酸基团的两性离子共轭聚电解质的应用

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2012247051B2 (en) * 2002-09-06 2015-02-19 Cerulean Pharma Inc. Cyclodextrin-based polymers for therapeutics delivery
CN101519490A (zh) * 2009-04-02 2009-09-02 中国科学院长春应用化学研究所 含氨基酸或肽基团的水溶性聚合物及其制法和应用
EP2511290A1 (en) * 2011-04-15 2012-10-17 Centre National de la Recherche Scientifique Compounds binding to the bacterial beta ring
CN106083866A (zh) * 2016-07-07 2016-11-09 南京师范大学 一种精氨酸取代的酞菁衍生物及其合成方法和应用
CN108329460A (zh) * 2018-03-08 2018-07-27 山西大学 一种光动力杀菌聚合物及其制备方法和应用
CN110172156A (zh) * 2019-04-19 2019-08-27 华中科技大学 一种含有共轭聚合物的复合纳米粒子及其制备方法与应用
CN110408008A (zh) * 2019-07-04 2019-11-05 南京工业大学 具有空穴传输性能的带有氨基酸基团的两性离子共轭聚电解质的应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Conjugated Polyelectrolyte–Silver Nanostructure Pair for Detection and Killing of Bacteria;Xiaoyu Wang et al.;《Adv. Mater. Technol》;20170518;第2卷;1700033(1-10) *
含胍基抗菌聚合物的合成及应用;张浩 等;《化学进展》;20190321;第31卷(第5期);第681-689页 *
胍类抗菌聚合物的构建及应用;彭开美 等;《化学学报》;20160809;第74卷;第713-725页 *

Also Published As

Publication number Publication date
CN112480377A (zh) 2021-03-12

Similar Documents

Publication Publication Date Title
Zhang et al. Killing three birds with one stone: Near-infrared light triggered nitric oxide release for enhanced photodynamic and anti-inflammatory therapy in refractory keratitis
CN115433367B (zh) 一种卟啉类cof材料及制备方法和应用
KR20060111536A (ko) 생물학적 활성 메틸렌 블루 유도체(２)의 개발
Zhdanova et al. Synthesis and photodynamic antimicrobial activity of amphiphilic meso-arylporphyrins with pyridyl moieties
Özkan et al. A [5] Rotaxane‐Based Photosensitizer for Photodynamic Therapy
CN112480377B (zh) 一种以精氨酸为侧链的共轭聚合物的制备方法及其应用
CN111187299B (zh) 一种基于噻吩并[3,4-b]噻吩的有机光敏剂及制备方法和应用
CN108329460B (zh) 一种光动力杀菌聚合物及其制备方法和应用
Sun et al. Tertiary amines convert 1O2 to H2O2 with enhanced photodynamic antibacterial efficiency
Yan et al. Antimicrobial photodynamic therapy for the remote eradication of bacteria
CN113425850B (zh) 光敏抗菌的改性卟啉金属有机骨架材料及其制备方法
CN108467475B (zh) 一种环状聚合物及其制备方法和应用
Wang et al. Bioactive AIEgens tailored for specific and sensitive theranostics of Gram-positive bacterial infection
CN111943868B (zh) 一种含二乙胺的吖嗪联肼类化合物及其制备方法与应用
Fan et al. Synthesis and photothermal/photodynamic antimicrobial activities of phthalocyanines tetra-substituted by morpholinyl moieties
Pujari et al. Design and synthesis of metalloporphyrin nanoconjugates for dual light-responsive antimicrobial photodynamic therapy
CN106035351B (zh) 一种负载光敏剂的聚合物胶束的制备方法及该胶束在浮游细菌、细菌生物被膜杀灭中的应用
Liang et al. A highly sensitive magnetic nano-fluorescent probe for singlet oxygen detection and screening of natural photosensitizers
CN116354954A (zh) 一种靶向溶酶体的aie探针及其制备方法与应用
CN116726194A (zh) 一种卟啉-抗生素超分子纳米颗粒和制备方法及其应用
CN107789623B (zh) 哌嗪取代硅酞菁及其在光热治疗中的应用
CN111187226B (zh) 一种特异性杀伤革兰氏阴性菌的化合物及制备方法和应用
Liu et al. Nanomaterials as carriers to improve the photodynamic antibacterial therapy
CN113214297B (zh) 基于聚集诱导发光型的有机硼光敏剂及其对治疗多重耐药菌感染的应用
CN113292576B (zh) 一类基于三苯胺的光热小分子及其制备方法和应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant