一类新型大环内酯衍生物的合成及其生物活性研究

为了寻找高效、广谱的杀虫、杀菌剂,以去糖基或部分去糖基的多杀菌素为母体进行结构修饰,合成了8种大环内酯酰化衍生物,其结构经1H NMR,13C NMR和MS表征.对合成的化合物进行了生物活性测试.结果表明,这类化合物对鳞翅目、鞘翅目、双翅目、半翅目及线虫等害虫有较好的杀灭活性,其中化合物3e在100 mg/L浓度下对桃蚜的24 h杀灭率达到100%,化合物3f和3h在上药量为200μg时对假单胞菌有一定的抑制作用.     

有机光敏剂结构与性能调控及其光诊疗应用

光动力治疗(Photodynamic Therapy,PDT)作为一种新兴的高效治疗方式,具有毒性低、非侵入性和可控等优点,已被广泛用于增生性皮肤疾病和肿瘤等疾病治疗.然而,已开发的PDT光敏剂在实际生物应用中仍面临诸多挑战,如:肿瘤乏氧环境降低治疗效果,光敏剂靶向性差易造成对正常组织的损伤.为了解决上述问题,研究者们开发了许多有效改善有机光敏剂治疗效果的方法.在此,主要综述了有机光敏剂的结构与性能调控策略.此外,对有机光敏剂在抗肿瘤、抗菌治疗以及余辉成像中的应用进行了介绍.最后,对有机小分子光敏剂的设计策略进行了总结与展望,以期促进该领域的发展.     

唾液酸酶和唾液酸糖基转移酶的结构、功能与催化反应研究进展

唾液酸酶和唾液酸糖基转移酶在生物体内许多重要的生理过程中发挥着不可或缺的作用.一般而言,唾液酸酶可以断裂糖缀合物末端与唾液酸残基相连接的糖苷键而水解唾液酸糖缀合物;唾液酸糖基转移酶以CMP-Neu5Ac为底物将唾液酸残基转移至新的糖基受体上.综述了与唾液酸相关的酶的分类、结构与催化反应机理;唾液酸酶和唾液酸糖基转移酶催化反应在有机合成中的应用;以及唾液酸酶的检测方法.对未来与唾液酸相关的酶的研究与应用进行了展望.     

光敏剂在癌症诊断和治疗中的研究新进展

光敏剂在特定波长的光照射下,产生荧光和单线态氧,已广泛应用于癌症的诊断和治疗.当前的研究热点是如何提高光敏剂的肿瘤选择性,尤其是光敏剂的靶向输送和特异性激活两方面.本文系统评述了提高光敏剂肿瘤选择性的方法及其在癌症诊断和治疗中的应用.引用文献56篇.     

靶标性酞菁类光敏剂的光动力疗法研究进展

光动力治疗（Photodynamic therapy,PDT）作为一种有别于传统癌症治疗方式的新型疗法,近些年来受到了科学家们越来越多的关注.它凭借着自身创伤性小,毒性低微,适用性好,可协同手术治疗以及可重复治疗等独特优势,在许多肿瘤的治疗方面有着广泛的应用.本文简要概述了光动力疗法的原理以及光敏剂的发展历程,并对理想光敏剂的特点作了总结.目前,以酞菁类化合物为主的第三代光敏剂已经成为光动力疗法的研究热点,然而如何提高光敏剂分子的靶向性达到精准的光动力治疗仍然是亟待解决的问题.因此,主要综述了近年来靶向性酞菁类光敏剂的研究进展,并对未来光敏剂的重点研究方向做出了展望.从目前来看,如何克服癌症低氧微环境的限制,发展Type I型不依赖氧的体系以及光穿透力强的靶向光敏剂在光动力治疗方面存在着巨大的潜质,有望成为新一代十分优良的光动力疗法用光敏剂.     

糖基异硫氰酸酯的合成及其应用

作为一类重要的有机合成中间体,糖基异硫氰酸酯广泛地应用于具有生理活性化合物的制备。本文对糖基异硫氰酸酯的结构、制备方法,以及作为中间体在糖基硫脲、糖基杂环、胍基糖苷、糖基缀合物等重要化合物的合成中的应用作了较详尽阐述。在对这些研究现状进行分析的基础上,对该研究领域下一步的发展方向提出了我们的观点。     

卟啉类第二代光敏剂的发展

本文对目前用于光动力治疗的以卟啉为基础的第二代光敏剂进行了综述, 这些光敏剂中的大部分已进入临床或临床前试验, 光物理性质研究表明它们是很有前途的光动力药物. 本文同样介绍了连接生物分子和硼烷的卟啉衍生物, 作为光疗剂, 它们具有非常光明的前途.     

新型利巴韦林衍生物的合成

以1-(2,3,5-三乙酰基-β-D-呋喃核糖基)-1,2,4-三氮唑-3-甲酸甲酯为原料,经水解和氨化反应得中间体1-(β-D-呋喃核糖基)-1,2,4-三氮唑-3-碳酰肼(3);以3为母体与芳香醛反应,对三氮唑3-位上碱基进行改性,合成了6种Sch iff碱利巴韦林衍生物,其结构经1H NMR和IR表征,其中3种为新化合物。     

光敏剂存在下乙氧羰基甲烯对己烷的插入反应和己烷的光敏氧化

本文对光敏剂二苯甲酮存在下,重氮乙酸乙酯光解所产生的乙氧羰基甲烯对已烷的插入反应进行了研究,并与无光敏剂时的插入反应进行了比较.发现光敏剂的存在不影响插入产物性质和它们的分配比例.同时,发现作为三线态猝灭剂的氧的存在对这些反应也没有影响.这些实验结果表明,对己烷的插入反应是由单线态的乙氧羰基甲烯进行的.对在二苯甲酮存在下已烷被空气光氧化的产物进行了仔细的分离和鉴定.结果表明,得到的是2-位和3-位已基自由基偶联和氧化的产物,因此看来,伯位的已基自由基在进行偶联和氧化反应之前先要转位成热力学上比较稳定的仲位自由基。     

基于光敏剂的纳米诊疗载体构建的研究进展

光动力疗法是一种很有前景的癌症治疗方法,光敏剂作为其核心,在被一定波长的激发光照射下产生荧光,因此光敏剂具有荧光成像诊断的潜力.然而光敏剂多是芳香共轭结构的疏水分子,存在易聚集结晶和溶解度差的问题.本文综述了近五年有关改善光敏剂缺陷,提高光敏剂对癌症的治疗和诊断的研究成果.具体从肿瘤微环境、肿瘤靶向性和改善荧光淬灭三个...     

Photophysical properties of glucoconjugated chlorins and porphyrins and their associations with cyclodextrins

Glucoconjugated analogues of the meta-hydroxyphenyl porphyrin (m-THPP) and meta-hydroxyphenyl chlorin (m-THPC) has been recently synthesized. The characteristics of their triplet states have been determined with regard to their involvement in the photodynamic (PDT) efficiency. In the case of porphyrin derivatives, triplet quantum yields (Phi(T)) were ranging from 0.42 to 0.55 and triplet life times (tau(T)) from 1 to 5 micros. High reaction rate constants (k(q)) with molecular oxygen (k(q): 1.2-1.6 x 10(9)s(-1)) have been found. The triplet lifetimes of chlorin derivatives were about four times higher than those of porphyrins whereas the Phi(T) and k(q) values remained quite similar. Singlet oxygen yields of glucosylated and non-glucosylated porphyrins and chlorins were not significantly different within experimental errors (Phi(Delta)((1)O(2)): 0.41-0.58). Furthermore, it has been shown that glucoconjugated photosensitizers could undergo associations with the methyl-beta-cyclodextrin (Me-beta-CD) which exhibit high triplet lifetimes and singlet oxygen yields ranging from 0.27 to 0.48.     

具有强可见光吸收的富勒烯-Bodipy衍生物作为光催化剂在硫醚光催化氧化中的应用

以氟硼吡咯染料（Bodipy）做为光吸收天线,富勒烯作为分子内自旋转换单元,分别利用前者的强吸光以及后者的高效系间窜越的优点,制备了吸收波长灵活可调、无重原子、具有强可见光吸收能力、长寿命三重激发态（92.1 μs）的二元（Dyad）、三元化合物（Triad）做为有机三重态光敏剂;其中Triad具有宽谱带可见光吸收能力,提高了光敏剂参与的分子间能量转移或电子转移过程的效率。与传统的Ru（Ⅱ）配合物等三重态光敏剂相比,光催化硫醚氧化的反应时间大大缩短。通过吉布斯自由能的计算、活性氧物种的捕获实验、电子顺磁共振等方法,证明了在光催化氧化硫醚的反应过程中,同时存在超氧负离子自由基和单线态氧两个活性物种,从而加快了光催化氧化反应速率。该研究结果将对新型有机三重态光敏剂的分子结构设计以及在光催化有机合成反应中的应用起到一定的促进作用。     

可双光子激发的聚集诱导发光光敏剂及其生物医学应用

综合评述了双光子激发的聚集诱导发光(AIE)光敏剂的研究进展, 重点讨论了双光子激发的AIE光敏剂的设计思路及在生物医学中的应用, 并对其发展前景进行了展望.     

Eradication of Gram‐Positive and Gram‐Negative Bacteria by Photosensitizers Immobilized in Polystyrene

Immobilization of photosensitizers in polymers opens prospects for their continuous and reusable application. Methylene blue (MB) and Rose Bengal were immobilized in polystyrene by mixing solutions of the photosensitizers in chloroform with a polymer solution, followed by air evaporation of the solvent. This procedure yielded 15–140 μm polymer films with a porous surface structure. The method chosen for immobilization ensured 99% enclosure of the photosensitizer in the polymer. The antimicrobial activity of the immobilized photosensitizers was tested against Gram‐positive and Gram‐negative bacteria. It was found that both immobilized photosensitizers exhibited high antimicrobial properties, and caused by a 1.5–3 log₁₀ reduction in the bacterial concentrations to their total eradication. The bactericidal effect of the immobilized photosensitizers depended on the cell concentration and on the illumination conditions. Scanning electron microscopy was used to prove that immobilized photosensitizers excited by white light caused irreversible damage to microbial cells. Photosensitizers immobilized on a solid phase can be applied for continuous disinfection of wastewater bacteria.     

电子转移光氧化反应在有机合成中的应用

电子转移光氧化反应与光敏化的单重态氧反应是光氧化反应的两个最重要的组成部分。电子转移光氧化是随着光诱导电子转移反应研究的广泛开展而得以迅速发展的。近年来,与光诱导电子转移反应有密切关联的过渡金属配合物的可见光催化反应也已成为研究热点。一些过渡金属配合物催化的电子转移光氧化反应也已出现。本文根据电子转移光氧化反应的不同机理,对这些反应进行分类,介绍了不同类型的电子转移敏化剂（包括氰基芳烃类光敏剂、鎓盐类阳离子光敏剂、过渡金属配合物类光敏剂以及有机染料类光敏剂）引发的电子转移光氧化反应,并讨论了各类电子转移光氧化反应中底物的各种活性中间体、反应中氧的活性形式、可能的反应途径以及在有机合成中的应用。     

Porphyrin and Nonporphyrin Photosensitizers in Oncology: Preclinical and Clinical Advances in Photodynamic Therapy

Photodynamic therapy (PDT) is now a well-recognized modality for the treatment of cancer. While PDT has developed progressively over the last century, great advances have been observed in the field in recent years. The concept of dual selectivity of PDT agents is now widely accepted due to the relative specificity and selectivity of PDT along with the absence of harmful side effects often encountered with chemotherapy or radiotherapy. Traditionally, porphyrin-based photosensitizers have dominated the PDT field but these first generation photosensitizers have several disadvantages, with poor light absorption and cutaneous photosensitivity being the predominant side effects. As a result, the requirement for new photosensitizers, including second generation porphyrins and porphyrin derivatives as well as third generation photosensitizers has arisen, with the aim of alleviating the problems encountered with first generation porphyrins and improving the efficacy of PDT. The investigation of nonporphyrin photosensitizers for the development of novel PDT agents has been considerably less extensive than porphyrin-based compounds; however, structural modification of nonporphyrin photosensitizers has allowed for manipulation of the photochemotherapeutic properties. The aim of this review is to provide an insight into PDT photosensitizers clinically approved for application in oncology, as well as those which show significant potential in ongoing preclinical studies.     

Dithiaporphyrin derivatives as photosensitizers in membranes and cells

We synthesized a series of analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin (I) as potential photosensitizers for photodynamic therapy (PDT). The photosensitizers differ in the length of the side chains that bind the carboxyl to the phenol at positions 10 and 15 of the thiaporphyrin. The spectroscopic, photophysical, and biophysical properties of these photosensitizers are reported. The structural changes have almost no effect on the excitation/emission spectra with respect to I's spectra or on singlet oxygen generation in MeOH. All of the photosensitizers have a very high, close to 1.00, singlet oxygen quantum yield in MeOH. On the contrary, singlet oxygen generation in liposomes was considerably affected by the structural change in the photosensitizers. The photosensitizers possessing short side chains (one and three carbons) showed high quantum yields of around 0.7, whereas the photosensitizers possessing longer side chains showed smaller quantum yield, down to 0.14 for compound X (possessing side-chain length of 10 carbons), all at 1 microM. Moreover a self-quenching process of singlet oxygen was observed, and the quantum yield decreased as the photosensitizer's concentration increased. We measured the binding constant of I to liposomes and found Kb = 23.3 +/- 1.6 (mg/mL)-1. All the other photosensitizers with longer side chains exhibited very slow binding to liposomes, which prevented us from assessing their Kb's. We carried out fluorescence resonance energy transfer (FRET) measurements to determine the relative depth in which each photosensitizer is intercalated in the liposome bilayer. We found that the longer the side chain the deeper the photosensitizer core is embedded in the bilayer. This finding suggests that the photosensitizers are bound to the bilayer with their acid ends close to the aqueous medium interface and their core inside the bilayer. We performed PDT with the dithiaporphyrins on U937 cells and R3230AC cells. We found that the dark toxicity of the photosensitizers with the longer side chain (X, VI, V) is significantly higher than the dark toxicity of sensitizers with shorter side chains (I, III, IV). Phototoxicity measurements showed the opposite direction; the photosensitizers with shorter side chains were found to be more phototoxic than those with longer side chains. These differences are attributed to the relationship between diffusion and endocytosis in each photosensitizer, which determines the location of the photosensitizer in the cell and hence its phototoxicity.     

Synthesis of Polymer-bound Sensitizers and their Applications in the Preparation of Previtamin D3 from Tachysterol

Two kinds of polymer-bound photosensitizers were synthesized, in which anthracene acts as sensitizer moiety,polystyrene (PS) and poly(methyl methylacrylate) (PMMA) serve as solid phase supports, respectively. The photoisomerization of tachysterol to previtamin D3 was carried out with these polymer-bound photosensitizers in ethanol and toluene solutions. The experiment results demonstrate that these solid phase photosensitizers are efficient for the photoisomerization with good recycle property and can be simply separated from the reaction mixtures by filtration.     

多酸基光敏剂在染料敏化太阳能电池中的应用

染料敏化太阳能电池(dye-sensitized solar cells,简写为DSSCs)是由Michael Gr覿tzel等开发的第三代光伏电池,它具有低成本、制作简单、光学性能可调、光电转换效率高等优势。其中光敏剂是DSSCs的重要组成部分,通过吸收可见光将电子传递到半导体导带,对整个电池的电子循环至关重要。广泛采用的光敏剂为N719等贵金属配合物,但其价格非常昂贵,很难实现大规模产业化。因此寻找低成本的非贵金属光敏剂是该领域的一项挑战。多金属氧酸盐(简称多酸,Polyoxometalates,简写为POMs)是一类具有纳米尺寸的分子基纳米材料,是分子型无机类半导体材料。多酸的富氧表面可以被活化和修饰,吸收光谱可以覆盖可见区甚至近红外区,具有合适的氧化还原电势,良好的热稳定性和溶解性。近年来,一系列研究表明多酸可以作为光敏剂应用在DSSCs中。本文中,我们以课题组多年来在POMs和太阳能电池领域的研究工作积累以及国内外同行专家的研究工作为基础,对多酸基光敏剂在DSSCs中的应用进行了详细综述。首先我们阐述了DSSCs的研究意义、多酸的简介、多酸的能级测量及调控。之后我们重点综述了多酸作为DSSCs中的光敏剂和共敏剂的研究。最后,我们对多酸基光敏剂在DSSCs领域的发展前景进行了总结和展望。本文有望引起多酸化学、材料化学及新兴交叉学科领域研究者的广泛研究兴趣,并为太阳能电池光敏剂的研究提供新的思路。     

Novel Photosensitizers Based on Polysaccharides – Dextran Modified with Anthracene

Summary : Series of novel water-soluble photosensitizers based on dextran was synthesized and studied. Dextran was modified by covalent attachment of anthracene chromophores. Photophysical and photochemical properties of the photosensitizers in aqueous solutions were determined. Their applicability for sensitization of oxidation of polynuclear aromatics and degradation of pesticides was demonstrated. Removal of photosensitizers from the environment after their usage was discussed.