符合经典构效关系的抗肿瘤铂类药物

综述了自顺铂、卡铂后符合经典构效关系的铂类抗肿瘤药物的发展概况，按载体配基和离去基团的结构特征进行了分类，总结了各类配合物的构效关系和临床进展，其中重点对手性二胺配体的铂(Ⅱ)配合物进行了介绍。并讨论了顺铂、卡铂、奥沙利铂的作用机理。     

非经典铂类抗肿瘤药物研究

本文综述了非经典铂类抗肿瘤药物的发展概况,介绍了具有口服活性的铂(Ⅳ)配合物,具有空间位阻的铂(Ⅱ)配合物,反式铂(Ⅱ、Ⅳ)配合物,多核铂(Ⅱ)配合物和含有铂-硫键的铂(Ⅱ)配合物,并总结了这几类新型铂配合物的抗肿瘤机理,克服顺铂的耐药性机理及其临床进展。     

顺铂,碳铂与鸟苷,L—蛋氨酸反应动力学比较研究

自发现顺铂具有抗癌活性以来,人们一直致力于它的抗癌机理研究。很多结果表明顺铂与蛋白质核苷酸(DNA)作用时主要与DNA中鸟嘌呤的N_7配位,通过形成链内交联作用造成DNA损伤。顺铂在显示抗癌活性的同时,也表现出较强的毒副作用,有文献认为毒性可能与形成Pt—S键抑制生物体内的巯基酶有关。     

抗肿瘤多核铂配合物的研究

多核铂配合物作为非经典铂抗肿瘤药物,其抗肿瘤机制与现有铂类抗肿瘤药物不同,因而在克服现有铂类抗肿瘤药物耐药性方面有着巨大的潜力。本文综述了多核铂类抗肿瘤药物的研究进展,以连接铂原子的桥配体结构的不同,可分为六大类:以烷基二胺及其衍生物为桥的多核铂配合物、以含氮杂环为桥的多核铂配合物、以羧酸根为桥的多核铂配合物、以卤素离子为桥的多核铂配合物、以含硫配体为桥的多核铂配合物及以其他配体为桥的多核铂配合物。本文还介绍了这几类多核铂配合物的抗肿瘤机理及在克服顺铂耐药性机理方面的研究进展。     

顺铂和反铂与红细胞膜糖蛋白的相互作用

用凝胶电泳法、荧光分光度法和圆二色谱研究顺铂和反铂与人红细胞膜糖蛋白的作用结果表明，顺铂在糖蛋白上的结合量明显高于反铂，顺铂对糖蛋白构象的影响也大于反铂，这提示顺铂的抗癌作用可能与膜糖蛋白的作用有关。     

铂(Ⅱ)配合物跨人红细胞膜传递的动力学研究

顺铂(cis-DDP)和顺式1,1-环丁烷二羧基二胺合铂(Ⅱ)(即卡铂,CBDCA)具有良好的抗癌活性,其主要靶分子均为DNA。但这些配合物与DNA作用前必须首先通过细胞膜。离体肿瘤对顺铂的摄入要比卡铂快得多,海拉细胞(Helas-3)摄入顺铂的速度要比摄入K_2PtCl_4或K_2PtCl_6慢。Binks等研究了鼠小肠摄取顺铂和卡铂的动力学机理,指出这两种配合物     

顺铂耐药的分子机制

顺铂被广泛用于多种类型的实体肿瘤的临床治疗.DNA是顺铂的主要靶点,顺铂结合会导致DNA损伤并诱发细胞凋亡.然而,顺铂化疗常常受到内在的和获得性的耐药性的限制.在过去30多年里,大量的研究致力于对顺铂耐药性的理解,并且提出了几种导致顺铂耐药性的分子机制.这些机制显示顺铂的耐药性具有多因素特征.本文系统描述和讨论了顺铂的耐药性机制,包括细胞内药物积累的减少,药物去活作用的增强,DNA修复作用,DNA损伤反应和凋亡通路的变化以及一些间接信号通路的调控影响.     

顺-二氯二氨合铂(Ⅱ)与红细胞膜蛋白的相互作用

顺铂可与红细胞膜蛋白结合,并使膜收缩蛋白交联聚合,巯基是顺铂的可能结合部位,顺铂造成膜蛋白构象或在膜内组装的改变,这些结果支持了我们提出的顺铂作用的多靶分子模型。     

致癌机理的阐明和高选择性抗癌剂的合成

1979年, 戴乾圜提出的化学致癌机理的双区理论发现: 环境致癌剂均代谢成特定的双官能烷化剂, 并通过诱发DNA互补碱基交联而启动癌变. 戴乾圜当时解释互补碱基交联启动细胞癌变的根源时指出: DNA即基因的突变主要都是由缺乏互补模板的交联的互补碱对所诱发(易于依靠互补模板修复的单个碱基损伤只有远为次要的作用), 而突变的基因借逆转录机制经历潜伏期而引起细胞的深度突变即奇异染色体的产生和细胞的最后癌变. 致癌剂的致突变谱、癌细胞中奇异染色体的结构、逆转录机制在正常细胞中的广泛存在和致癌剂均能诱发DNA股间交联等, 都从实验上证明了双区理论所揭示的上述致癌过程的分子机理. 传统的抗癌剂都是基因毒性的, 即抗癌剂均具有强力的致癌、致畸胎、致不育和致突变的潜力. 作者首次将致癌剂的抗癌药效和基因毒性的差别, 定义为抗癌剂的选择性. 作者发现可以突破抗癌剂的随机筛选和偶然发现的方式, 借双区理论按照理论预想设计高选择性抗癌剂. 实践证明: 抗癌烷化剂本身或代谢后都是双官能烷化剂. 戴乾圜将双官能抗癌烷化剂在DNA碱基之间的交联, 划分为易于修复的股内或股间非互补碱基间的、不具致癌性的良性交联, 和难于修复的互补碱基间的、表现致癌性的恶性交联. 因此双区理论设计高选择性抗癌剂的理论观点认为: 应力求抑制恶性交联而强化良性交联. 在双区理论指导下合成了总称为双区铂系列的铂络合物, 其中一系列顺式二取代苯甲胺合二卤合铂(II)进行了细胞和动物药效学实验. 当时已知的主导性抗癌剂顺铂是癌细胞灭杀率和动物疗效最高的抗癌剂. 但若干双区铂对各种癌细胞的灭杀率均超过了顺铂, 文中援引的四个双区铂系各对小鼠肉瘤S₁₈₀的抑瘤率和小鼠白血病L₁₂₁₀的延寿率均分别超过顺铂, 而其毒性均远较顺铂为低. 毒性远低于顺铂而实验动物疗效超过顺铂的药物, 至今尚未见有其他实例. 根据双区理论和群论的预想设计, 对碳铂(卡铂)作了增加一个CH₂的最小结构修饰, 合成了新化合物顺式-二氨合环戊烷-1,1-二羧酸根合铂(II), 命名为铭铂. 铭铂的水溶性较碳铂高一倍, 油溶性远高于碳铂, 动物急性毒性较碳铂低一倍, 对快速生长的腹水型动物瘤株的疗效, 显著性地高于碳铂. 双区理论预想设计的铭铂的低基因毒性得到了实验的证明, 铭铂以对TA 102株回复突变度量的基因毒性较顺铂低200倍, 较碳铂低10倍, 对所有受试妊褥母鼠的子代均没有致畸胎作用. 铭铂用于临床以后, 世界上第一个按照预想合成的高选择性抗癌剂将在癌化疗上显示何等的效果, 则将拭目以待. 此外, 借双区理论解释了近来抗癌铂络合物的若干经验性研究, 并试行从选择性的角度予以评介.     

铂与社会

铂是一种重要的贵金属,是化工、能源、石油炼制上的常用催化剂,是冶金工业制备高温电阻温度计的必须材料,是制造白金首饰的基本原料.铂的化合物——顺铂更是目前结构最简单的抗癌药物.本文概述了铂的性质、应用和工业制法,介绍了白金首饰的类型和检验方法,顺铂的抗癌机理.     

Organometallic ruthenium-based antitumor compounds with novel modes of action

Both metal complexes and organic molecules are widely used for the treatment of various diseases including cancer - in addition to surgery and radiotherapy. Recent years have witnessed a surge of interest in the application of organometallic compounds to treat cancer and other diseases. Indeed, the unique properties of organometallic compounds, intermediate between those of classical inorganic and organic materials provide new opportunities in medicinal chemistry. In this review, based on the award lecture at ICBOMC’10, we describe a class of ruthenium(II)-arene complexes that are weakly cytotoxic in vitro, but show selective antimetastatic activity in vivo. These compounds, [Ru(η⁶-p-arene)Cl₂(pta)] termed RAPTA, interact strongly with proteins, with the ability to discriminate binding to different proteins, but show a relatively low propensity to bind DNA, which is considered to be the main target of many metal-based drugs. The basic RAPTA structure is quite stable in physiological environments, and studies have shown that aquation of the chloride bonds occurs, it may not be an essential step for anticancer drug activity - direct substitution with biomolecular targets is also possible. Based on the favorable physicochemical properties of RAPTA compounds, combined with their highly promising pharmacological properties, the structure represents an ideal scaffold for rational drug design. Thus far, strategies to overcome drug resistance, by interference with critical enzymes responsible for drug deactivation, and tumor targeting, by tethering to human serum albumin via hydrolyzable linkers, have been demonstrated. However, many more approaches can be envisaged. In any case, the net result are a type of hybrid compounds, that occupy a niche somewhere between classical cisplatin-type anticancer agents that are widely applied to many tumor types and targeted therapies based on organic structures used to inhibit specific enzymes. As such, should these compounds prove themselves in the clinic it is not inconceivable that they could be rapidly refined to form personalized chemotherapies.     

石墨炉内石墨探针表面上的原子化机理研究(Ⅴ)——锰的原子化机理

在石墨炉原子吸收光谱(GFAAS)法中,反应前后的化合物形态可以借助于X射线衍射(XRD)、俄歇电子能谱(AES)及化学分析光电子能谱(ESCA)等现代分析仪器来鉴定,本文综合利用上述分析方法,对锰化合物在石墨探针表面上于不同温度下的化学形态进行鉴定,结合元素的灰化和原子化曲线,详细地研究和阐述了锰的原子化机理。     

Thymol bioactivity: A review focusing on practical applications

Thymol is a natural volatile monoterpenoid phenol that is the main active ingredient of oil extracted from species Thymus vulgaris L., commonly known as thyme, and other plants such as Ocimum gratissimum L., Origanum L., Carum copticum L., different species of the genus Satureja L., Oliveria decumbens Vent, and many others. It is a versatile molecule with a wide variety of practical applications such as medical, dentistry, veterinary, food, and agrochemicals, among others. Its pharmacological applications have been the most investigated and reported, focusing on its prominent antimicrobial, antioxidant, anti-inflammatory, cicatrizing activities. Furthermore, it is noteworthy that the research on its agricultural applications has increased, highlighting its uses as a natural agrochemical and preservative to safeguard foods from pathogenic microorganisms both in sowing and storage, which could have a beneficial effect on human health and the environment. Research has also been reported on its activity as an insecticide, acaricide, and animal repellent. This review summarizes important aspects of thymol such as its bioavailability, synthesis, and biological activities, with special interest in practical applications.     

硝基胍热解反应途径的量子化学研究

本文用MINDO/3方法研究了硝基胍热解反应的机理。研究结果表明, 硝基胍热解反应可经历两条途径得到主产物(N_2O、H_2O和NH_3)。这两条途径相互竞争, 但生成N_2O及H_2O的途径Ⅰ要容易进行, 是整个反应的启动步。     

（CH3）3NO存在下M（CO）5（M＋Fe,Ru,Os）的CO取代反应动力学研究

在(CH_3)_3NO存在下,PPh_3取代M(CO)_5(M=Fe,Ru,Os)中CO的反应速度遵循二级速度定律,分别与[M(CO)_5]和[(CH_3)_3NO]的一次方成正比,与[PPh_3]无关。反应速度按FeRu>Os的次序约减小4倍。 1 实验方法 典型的动力学实验中,将(CH_3)_3NO的C_2H_5OH溶液和PPh_3的己烷溶液分别用注射器加到体积合适的烧瓶中,再注入Fe(CO)_5并迅速震荡烧瓶,再取出一部分反应液立即注入充N_2     

Photophysical insights on quantum dots-zinc porphyrazine system studied in solution

The present study reports spontaneous interaction of a quantum dots, namely, CdS_xSe_1-x/ZnS (QD) with zinc porphyrazine (1) in toluene. It is observed from steady state fluorescence measurements that photoluminescence of QD suffers quenching by 1. Time resolved fluorescence measurements reveal small change in the lifetime of QD (16.10 ns) following it interaction with 1 (15.77 ns). The magnitude of k_q for QD-1 system, i.e., k_q ​= ​5.25 ​× ​10¹² ​L⋅mol⁻¹⋅sec⁻¹ (evaluated from the stern-volmer plot) establishes that photoexcited QD undergoes decay by 1 according to static quenching mechanism. The results emerging from above study confirm that QD-1 system may be judiciously applied as an energy storage material in near future.     

Deformation Potential Approach to the Calculation of Mobilities of Carriers and Conductivity of trans-Polymonocyanoacetylene

The deformation potential theory for one-dimensional organic polymer is studied. This approximation is then used to calculate the mobilities of carriers and the conductivity of trans-polymonocyanoacetylene (PMCA). The results of calculations are in fairly good agreement with experimental data.     

Overview on multicomponent ceramic composite materials used for efficient photocatalysis – An update

Water is an important item for the survival of humans, animals and plants in the planet earth. In the industrialized world, water pollution is raising every day, mainly in the textile, paper, medicine, and plastic production industries. Pollution from coloured compounds is primarily identified as being the major threat to wastewater. In the absence of any pre-treatment, substituted phenols, dyes and agricultural wastes seriously contaminate groundwater systems. For the removal of dyes from the industrial waste water, the following three traditional methods are used: chemical, physical and biological but, the cost of the methods little high. For alternation of these methods, now a days photocatalytic degradation method was used. Metal and metal oxide nanoparticles are excellent catalysts for reducing and degrading aqueous phase nitro compounds and aromatic dyes. Nanoparticles are commonly assembled into two types, i.e., organic (carbon nanoparticles) and inorganic (metal, semiconductor and magnetic nanoparticles) nanoparticles. In this review article we are mainly focused on the behaviour of different types of pure metal oxides and metal oxide@metal/metal oxide/carbon/polymer nanocomposites for the removal of various organic pollutants from water and their efficiency has been reported. As a result of their review the cerium-based metal oxides such as CdS/CeO₂, CeO₂/Y₂O₃, GQDs/CeO₂ and Ag/cellulose@CeO₂/QDs shows more degradation efficiency (above~95%) towards the organic pollutants when compared to other metal oxides.     

水溶性聚合物热稳定性研究进展

水溶性聚合物广泛应用于石油开采、水处理、造纸、印染以及医药等领域,该类聚合物热稳定性问题直接关系到其在高温环境下的应用性能,因此具有重要的研究意义和应用价值。本文选取了几类具有代表性的水溶性聚合物,详细综述了其热稳定性的研究进展,重点分析了不同类型的水溶性聚合物的热降解机理,并探讨了分子结构和外添加剂对热稳定性能的影响,最后对其发展前景进行了展望。