卟啉类光敏剂的研究进展

光动力疗法(photodynamic therapy,PDT)自问世以来,已成为治疗癌症的重要方法。作为PDT中最重要的因素,光敏剂(PS)的研究越来越受到重视。介绍了卟啉类光敏剂的发展过程,大致分为三代:第一代以血卟啉及其衍生物为主,第二代主要为结构明确的卟啉类化合物,第三代光敏剂为第二代光敏剂与功能性分子结合的产物。最后例举了部分近年来已药用的卟啉类光敏剂。     

[2, 7, 12, 18-四甲基-3, 8-二(-1-羟基乙基)-13, 17-二羧基乙基]-卟啉的改进合成

在酸性条件下,氯化血红素(Ⅰ)与还原性铁粉作用生成原卟啉(Ⅱ),通过HBr-冰醋酸加成不经提纯直接加入NaOH溶液,OH-取代仲位Br制得[2,7,12,18-四甲基-3,8-二(1-羟基乙基)-13,17-二羧基乙基]-卟啉(血卟啉,Ⅲ),反应总产率达到90.6%。探讨了脱铁过程中反应温度、时间、还原剂用量等因素对原卟啉(Ⅱ)合成的影响,反应时间和pH对血卟啉(Ⅲ)合成的影响。结果表明,当氯化血红素和铁粉的摩尔比为1∶1、反应温度为110℃时,原卟啉的产率最高达98.3%;当pH=10,反应时间为6 h时,血卟啉的产率最高达92.1%。通过IR、MS和1HNMR对产物结构进行了表征。     

美加净爱萝莉系列防晒剂抗光毒作用观察

小鼠皮下注射氯丙嗪和腹腔注射血卟啉衍生物(HPD)后,黑光灯(长波紫外线灯)照射24小间均可引起光毒反应,表现为鼠耳红、肿、局部组织坏死甚至脱落,而鼠耳局部涂擦美加净爱萝莉系列防晒剂对由氯丙嗪和HPD所引起的光毒反应均有防治作用,尤以防晒霜效果更佳。     

硼氢化-氧化法制备[2,7,12,18-四甲基-3,8-二(-2-羟基乙基)-13,17-二甲氧基羰基乙基]-卟啉

以氯化血红素(Ⅰ)为原料,经过脱铁、酯化、反马氏加成得到[2,7,12,18-四甲基-3,8-二(2-羟基乙基)-13,17-二甲氧基羰基乙基]-卟啉(异血卟啉二甲酯,Ⅳ)。在合成原卟啉二甲酯(Ⅲ)的过程中,采用了超声激励法,并且对反应条件进行了优化,产率达到91.6%;然后通过BH3-THF络合物同原卟啉二甲酯3,8-位乙烯基的反马氏加成合成了[2,7,12,18-四甲基-3,8-二(2-羟基乙基)-13,17-二甲氧基羰基乙基]-卟啉,并对加成体系进行适当优化,产率达到64.3%。通过1HNMR、MS、UV-vis和IR测试技术对产物结构进行了表征。     

D-A型卟啉衍生物作为光敏剂的影响因素

近年来,染料敏化太阳能电池(Dye-sensitized solar cell,DSSC)作为一种新型模拟自然界光合成原理的光伏电池得到了迅速发展,光敏剂的性能决定DSSC对光的利用。概述了卟啉衍生物作为光敏剂所具有的独到的结构优势,卟啉环上有多个可修饰的位点,且对光的利用率高,同时讨论了D-A型卟啉衍生物作为光敏剂的影响因素。     

四(4-氨基苯基)卟啉及其金属配合物的合成方法改进

以对硝基苯甲醛、吡咯为原料,戊酸为溶剂,经缩合反应合成得到四(4-硝基苯基)卟啉(TNPP),以此为基础经过还原得到四(4-氨基苯基)卟啉(TAPP),并进一步与金属盐反应合成得到金属配合物。利用紫外可见光谱、红外光谱、元素分析、质谱及核磁共振氢谱对卟啉及其金属配合物进行了结构表征,确定合成产物为目标产物。通过合成方法的改进,提高了四(4-氨基苯基)卟啉(TAPP)及其金属配合物的产率,产率与目前的文献值相比较从30%提高至38%,为进一步研究氨基卟啉类有机金属材料提供了新的合成思路和方法。     

光活性二茂铁衍生物的研究进展

具有光活性的二茂铁基功能材料以其独特的结构和性质而备受关注。光活性二茂铁衍生物是光动力疗法(Photodynamic Therapy,PDT)治疗癌症的主要成分,因其在杀死癌细胞的同时对机体毒害小,选择性好,可重复治疗等优点备受关注。含有共轭体系的二茂铁衍生物易发生非对称极化,表现出很大的非线性光学(nonlinear optics,NLO)光学响应,是优秀的光电学材料。综述了光活性二茂铁衍生物在PDT和非线性光学中的最新研究进展,并对研究方向进行了展望。     

超声波激励法改进合成[2,7,12,18-四甲基-3,8-二(-1-羟基乙基)-13,17-二甲氧基羰基乙基]-卟啉

以氯化血红素(1)为原料,经过加成和取代反应制得血卟啉(2)。然后在超声波激励下,以血卟啉(2)作为原料,浓硫酸作为催化剂,甲醇既作溶剂又作反应剂,合成了[2,7,12,18-四甲基-3,8-(-1-羟基乙基)-13,17-二甲氧基羰基乙基]-卟啉(血卟啉二甲酯,3),两步反应总产率达到74.8%。探讨了反应时间、催化剂用量以及超声功率对血卟啉二甲酯(3)合成的影响,并且将超声波激励法与加热搅拌法进行了比较。实验结果表明,同加热搅拌法相比,超声激励法反应时间更短,产率更高,副产物更少。产物结构通过1 H NMR、MS和IR测试技术进行了表征。     

蓝桉叶挥发油化学成分分析研究

采用乙醚为溶剂提取云南产蓝桉干叶的挥发油,经气相-质谱联用仪分析,得到57种组分,确定了其中54个化合物的结构,主要成分是1,8-桉叶素(68.61%),α-蒎烯(10.24%),别香橙烯(5.27%),乙酸松油酯(4.05%),香橙烯(1.45%),(-)-蓝桉醇(1.26%),α-松油醇(1.02%)等。采用峰面积归一法计算各组分的相对含量,所鉴定成分占总馏出峰面积的99.69%。     

酰胺基卟啉化合物的制备、表征及热分析

5-(4-氨基)苯基-10,15,20-三苯基卟啉(MATPP)与棕榈酸在CH2Cl2中直接反应,得到一种新型不对称酰胺基卟啉5-(4-棕榈酸酰亚胺基)苯基-10,15,20-三苯基卟啉(PITPPH2),利用紫外-可见光谱、红外光谱、核磁共振氢谱、元素分析等测试方法对化合物的结构加以确认。热分析表明,卟啉PITPPH2从200℃开始分解,具有较高的热稳定性。     

Absorption and fluorescence spectral properties of hematoporphyrin in liposomes,micelles, and nanoparticles

A model photosensitizer, hematoporphyrin (Hp), encapsulated in various nanocarriers was investigated for both absorption and fluorescence properties. The generation of singlet oxygen upon light activation was also studied. The absorption intensity of nanoencapsulated hematoporphyrin was stronger and exhibited a red-shift of the Soret and Q absorption bands compared to the non-encapsulated hematoporphyrin. The fluorescence spectral changes were similar to the absorption spectral pattern. The generation of singlet oxygen for encapsulated hematoporphyrin upon light activation differed significantly from the free form hematoporphyrin, and the yield of singlet oxygen production was found in the following order: liposomes > micelles ≈ nanoparticles > free Hp. Under the current studied conditions, the use of nanocarriers significantly improve the photophysical properties of hematoporphyrin in aqueous solutions, and the liposome was the optimum system than either the micelle or the nanoparticle.     

Photochemical investigations into cellulosic materials I. Free radical generation in cellulose by photosensitized excitation

UV irradiation of cellulose, both in photosensitized and unphotosensitized experiments results in chain scission and radical generation on the glucosidic cycle, as observed by ESR spectroscopy. It was shown that sensitizers of the benzoin and benzophenone family induce radicals very efficiently on cellulose. The results obtained with several benzoin derivatives and benzophenone are discussed in connection with the ESR spectra, in terms of the primary processes involved during the photolysis of these compounds in cellulose. Features relevant to photografting are derived from these experiments.     

硫杂蒽酮类光引发剂的电子自旋共振研究

本文采用ESR手段对五种硫杂蒽酮类光引发剂2-甲基硫杂蒽酮(MTX)2,4-二甲基硫杂蒽酮(DMTX)、1,2,4-三甲基硫杂蒽酮(TMTX)、2-甲氧基硫杂蒽酮(MOTX),2-戊氧基硫杂蒽酮(AOTX)和三乙胺引发体系进行了研究,提出了该类光引发剂和三乙胺暗反应的机理。     

In situ detection of hindered amine stabilizer consumption in polymer through oxidation by indirect electron spin resonance

The stabilization mechanisms of hindered amine stabilizers (HAS) involve various oxidation products of the piperidine structure. Thus, we propose a novel method, based on electron spin resonance (ESR) spectroscopy, to check in situ the consumption of the total piperidyl species (intact HAS and all of its byproducts) in polypropylene (PP) films through photooxidation. First, the concentration of nitroxyl radicals produced upon irradiation in stabilized PP has been measured by direct ESR analysis. Then, the changes of concentration of the overall stabilizing species have been detected by indirect ESR, after conversion of the overall HAS derivatives into nitroxyl-free radicals by exposure of photooxidized PP to peracetic acid vapor at room temperature. Results were compared with those obtained by the conventional Fourier transform infrared method in the particular case of [2,2,6,6-tetramethyl piperidinyl]sebacate, and the reliability of both techniques was discussed. Thus, we assume that indirect ESR experiments consist of a easy, accurate, and very sensitive method to monitor the time evolution of a low-molecular weight HAS–NH concentration in PP upon photooxidation. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 1107–1114, 1998     

Some observations on the mechanism of action of retarders in rubber vulcanization. A new class of retarder

Attempts have been made to demonstrate the involvement of free radicals in the benzthiazolesulfenamide-accelerated vulcanization of natural rubber. Free radicals were only detected by ESR in reaction mixtures containing the retarder N-nitrosodiphenylamine (NDPA). In addition, NDPA was the only compound found, from the vulcanization accelerator and retarders tested, to affect the free-radical polymerization of methyl methacrylate. A purely ionic mechanism for sulfur vulcanization of natural rubber accelerated by benzthiazolesulfenamide derivatives has therefore been assumed and used to help in the design of new vulcanization retarders. A new class of retarder has been discovered, consisting of hydrocarbylthio derivatives of trisalkylsulfonyl methane. These retarders are believed to be the first vulcanization retarders to act by cleavage of a carbon–sulfur bond.     

Distance measurement between Tyr10 and Met35 in amyloid beta by site-directed spin-labeling ESR spectroscopy: implications for the stronger neurotoxicity of Abeta42 than Abeta40

The neurotoxicity of the 42-mer and 40-mer amyloid beta peptides (Abeta42 and Abeta40) is closely related to the radicalization at both Tyr10 and Met35. Abeta42 is more neurotoxic than Abeta40. Our previous structural analyses of Abeta42 suggested that Tyr10 and Met35 are brought closer together by the turn at positions 22 and 23, and the S-oxidized radical cation at position 35, which is the ultimate toxic radical species, can be produced effectively through oxidation by the phenoxy radical at position 10. To verify this idea, their separation was measured by site-directed spin labeling (MTSSL) by using ESR spectroscopy. Among the three kinds of Abeta42 derivatives, which are doubly or singly spin-labeled at position 10 and 35, only 10,35-MTSSL-Abeta42 showed a clear dipole coupling in continuous-wave ESR; this suggests that the intramolecular spin labels at position 10 and 35 in Abeta42 are located within approximately 15 A. In contrast, 10,35-MTSSL-Abeta40 did not give such signals. The distance between Tyr10 and Met35 in 10,35-MTSSL-Abeta40, which was successfully measured by pulsed ESR spectroscopy was 30 A long. The difference in the distance between Abeta42 and Abeta40 could explain in part the stronger neurotoxicity of Abeta42 compared to Abeta40.     

Computations of ESR coupling constants in organic radicals. III. Nitro Derivatives of the Benzyl Radical

We compute the ESR coupling constants and the geometries of ten nitro derivatives of the benzyl radical. We consider the three mononitrobenzyls, the six dinitrobenzyls and 2,4,6-trinitrobenzyl. The computations are based on the use of the Gaussian 82 Program Package with the STO-3G basis set. There are no experimental data available.     

Electrochemical and ESR study of the CH bond activation. Electrocatalytical oxidation with participation of radical cation of phenazine-di-N-oxide

The mechanism of oxidation of organic substrates (cyclohexanol, ethanol, methanol, tetrahydrofurane, triethylether of orthoformic acid, dioxane, toluene and cyclohexane) in the presence of a mediator, electrochemically generated radical cation of phenazine-di-N-oxide, has been studied by the methods of ESR electrolysis and cyclic voltammetry. The study was carried out at Au, Pt and glass carbon electrodes in acetonitrile, as well as in methanol and its deuterated derivatives (CH₃OD, CD₃OD) used as a solvent and a substrate simultaneously. The effect of temperature, acids, water, oxygen, the nature of solvent, substrate and supporting electrolyte on the shape and intensity of ESR signal and cyclic voltammograms (CV) has been studied. ESR spectra of radical intermediates were revealed: one intermediate with g-factor 2.0023 in CH₃OH and CH₃OD and two intermediates with g-factors 2.0023 and 2.0036 in CD₃OD. The obtained results were explained by the overall two-electron mechanism of the electrochemical oxidation of the substrate via formation of the complex of substrate with the radical cation of phenazine-di-N-oxide.     

Computations of ESR Coupling Constants in Organic Radicals. II. Nitro derivatives of the phenyl radical

We compute the ESR coupling constants and the geometries of a set of nitro derivatives of the phenyl radical. We consider the three mononitrophenyls, the six dinitrophenyls and 2,4,6-trinitrophenyl. The computations are based on the use of the Gaussian 82 Program Package with the STO-3G basis set. There are no experimental data available.