基于金属的神经退行性疾病治疗策略*

本文综述了金属离子在神经退行性疾病中的重要作用以及针对该类疾病金属治疗药物的研究进展。以老年痴呆症和帕金森氏症为代表,结合本课题组的初步研究结果,讨论了金属离子在蛋白质聚集与氧化应激反应中的重要作用,暗示金属螯合策略应成为治疗该类疾病的首选策略,并介绍了数种已用于或即将用于临床实验的金属螯合制剂;还介绍了烷基化神经退行性疾病相关蛋白的金属结合位点,可以显著抑制该蛋白质聚集体的形成和活性氧的产生,这可能是继螯合策略后一种更有发展潜力的神经退行性疾病治疗方法。     

金属蛋白研究中几个值得注意的动向

本文叙述了金属蛋白和金属酶研究中近年来几个值得注意的发展动向，即与金属离子相关的疾病（特别是神经退行性疾病）、金属离子在蛋白质的折叠、聚集和装配中的作用，金属伴侣分子、金属蛋白的设计和构建、金属蛋白与DNA相互作用。     

过渡金属离子与神经退行性疾病

介绍过渡金属离子在神经退行性疾病中的作用和生物学意义,以及一种可能的金属作用下的神经退行性疾病致病机理。重点介绍铜离子在老年痴呆症、家族性肌萎侧索硬化症、克雅氏症等疾病的致病机理方面的作用。     

金属离子在生命过程中的作用机制

生命活动是一系列错综复杂的生物反应,包含着元素的获取、作用、代谢等生理过程。文章重点从机体组织构成、生长发育、能量和物质的新陈代谢、生物和神经信号的传递等不同生命活动中金属离子所起的作用及其作用机制进行了综述。结果表明金属离子在许多生命活动中起到了至关重要的作用。文章为生物元素调节、金属药物研制和疾病防治等应用提供了一定的理论基础。     

姜黄素抑制金属离子诱导的丝素蛋白构象转变及其作用机理

以丝素蛋白(SF)为神经退行性疾病相关蛋白的模型蛋白, 分析了姜黄素(Curcumin)对Zn(Ⅱ)和Cu(Ⅱ)离子诱导的丝素蛋白构象转变的干预作用及其作用机理, 试图探讨姜黄素在神经退行性疾病中的预防与治疗作用. 结果表明, 姜黄素可通过与Cu(Ⅱ)和Zn(Ⅱ)离子络合, 干预金属离子诱导的丝素蛋白构象转变, 并且所形成的络合物Cu(Ⅱ)-Curcumin可抑制丝素蛋白的构象转变, 但是Zn(Ⅱ)-Curcumin络合物不具有这种能力. 因此, 基于姜黄素对于金属离子诱导的丝素蛋白构象转变具有良好的干预作用, 可以将姜黄素作为神经退行性疾病预防和治疗的潜在候选药物.     

铜锌超氧化物歧化酶的突变与神经退行性紊乱的生物无机化学

本文简单介绍了铜锌超氧化物歧化酶的结构、功能及其相互关系,较为详细地讨论了与神经退行性紊乱,尤其是与肌萎性脊髓侧索硬化症有关的铜锌超氧化物歧化酶突变体的生物无机化学的研究进展,提出由该酶突变而引起的蛋白质局部结构变化和金属离子缺失,以及由此导致的氧化损伤和聚集作用可能是导致神经退行性紊乱的主要原因之一.     

铋膜电极差分脉冲溶出伏安法测定苹果和梨中的铅含量

随着科学技术的飞速发展和人民生活水平的不断提高，人们开始更多地关注自身健康，生命科学已经成为当今最活跃的研究领域之一。铅是一种污染重金属，它对机体的毒性作用越来越被人们所关注。铅通过皮肤、消化道、呼吸道进入体内多种器官，对神经、血液、消化、心脑血管、泌尿等多个系统造成损害，严重影响体内的新陈代谢，阻塞金属离子代谢通道而造成低钙、低锌、低铁，并导致补充困难，出现神经系统病症、代谢障碍。     

荧光共轭聚合物金属离子传感的机理研究

含金属离子识别单元[2,2′-联吡啶(bpy)、1,10-菲洛啉(phen)等]的荧光共轭聚合物金属离子传感的机理主要是引入金属离子所引起的聚合物主链构象的变化或是电子能级的变化.本文报导了两种属于这类荧光共轭聚合物的芴共聚物P1和P2在溶液中和固体薄膜状态下的金属离子传感性质,并研究了这类荧光共轭聚合物金属离子传感的机理.聚合物P1和P2分别是有20°二面角的bpy和平面的phen与芴交替共聚而成.研究发现P1、P2与金属离子络合后能够使吸收光谱红移,荧光猝灭,同时P2表现出更灵敏的金属离子传感性质.尤其是P2在固体状态下的高灵敏金属离子传感性质为金属离子荧光传感器的应用提供一种新的思路.P2的金属离子识别单元是平面的phen,在与离子响应过程中不需要发生构型转变,从而可以说明这类主链含金属离子识别单元的聚合物在与金属离子作用时,金属离子配位诱导聚合物电子能级的改变是金属离子传感的决定性因素.     

纳米材料修饰电极在重金属离子检测中的应用

本文介绍了近年来纳米材料修饰电极在重金属离子检测中的研究现状,分析了这些修饰电极的特点,重点阐述了纳米材料在重金属离子检测中的重要作用,列举了一些纳米材料修饰电极在重金属离子检测中的应用,最后对纳米材料修饰电极用于重金属离子的检测研究进行了简要评述和展望。     

金属调控蛋白的结构、性质及应用

金属调控蛋白是微生物体内通过转录抑制或激活机制严格控制金属离子摄入、外排和储存的特异性金属离子结合蛋白,对维持体内适宜的金属离子浓度和平衡起着举足轻重的作用。本文综述了目前主要的七大家族金属调控蛋白的调控机制和拓扑结构,详细介绍了金属离子结合区域的结构特征和金属-配体的配位构型。基于金属-配体的配位构型,重点讨论了每类金属调控蛋白对目标金属离子特异性选择的机理。此外,本文还介绍了金属调控蛋白在重金属离子检测和吸附方面的应用,拓展了金属调控蛋白的研究和应用领域,同时为生物无机化学的研究方向开辟了新的思路。     

Physical organic chemistry on the brain

The challenges to obtaining chemical-scale information on the molecules of neuroscience are considerable. Most targets are complex integral membrane proteins that are not amenable to direct structural characterization. However, by combining the tools of organic synthesis, molecular biology, and electrophysiology, rational and systematic structure-function studies can be performed in what we have termed physical organic chemistry on the brain. Using these tools, we have probed hydrophobic effects, hydrogen bonding, cation-pi interactions, and conformational changes associated with channel gating. The insights gained provide important guidance for drug discovery efforts targeting ion channels and neuroreceptors and mechanistic insights for the complex proteins of neuroscience.     

In vivo visible light-triggered drug release from an implanted depot

Controlling chemistry in space and time has offered scientists and engineers powerful tools for research and technology. For example, on-demand photo-triggered activation of neurotransmitters has revolutionized neuroscience. Non-invasive control of the availability of bioactive molecules in living organisms will undoubtedly lead to major advances; however, this requires the development of photosystems that efficiently respond to regions of the electromagnetic spectrum that innocuously penetrate tissue. To this end, we have developed a polymer that photochemically degrades upon absorption of one photon of visible light and demonstrated its potential for medical applications. Particles formulated from this polymer release molecular cargo in vitro and in vivo upon irradiation with blue visible light through a photoexpansile swelling mechanism.     

Analytical chemistry and inorganic chemistry — an unhappy marriage?

Summary Analytical chemistry is a discipline which has a large impact in other fields of chemistry and natural sciences as well as in technology and society. Traditionally, analytical chemistry has been grouped together with inorganic chemistry to such an extent that they are often viewed as a single discipline. While this has been beneficial for the development of both inorganic and analytical chemistry, it is increasingly important that the need of analytical education by the organic and biochemists as well as by chemical engineers is clearly recognized. The tightening environmental protection requires the analyst to be conversant with more sensitive, more accurate, and more reliable techniques in novel chemical surroundings, but at the same time he has to have as thorough knowledge in every field of chemistry as possible.     

Simple high-performance liquid chromatographic method for the concurrent determination of the amine metabolites vanillylmandelic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, dihydroxyphenylacetic acid and homovanillic acid in urine using electrochemical detection

A simple method for the concurrent analysis of the noradrenaline metabolites vanillylmandelic acid and 3-methoxy-4-hydroxyphenylglycol, the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid, and the serotonin metabolite 5-hydroxyindoleacetic acid in human urine is described. Following organic extraction of the metabolites from acidified urine, they are separated by single-step gradient elution high-performance liquid chromatography on a reversed-phase column. Detection and quantification are achieved with an electrochemical detector using a carbon-paste electrode; samples can be injected at 40-min intervals. Optimisation of analytical parameters is described, and examples of the application of the method in the fields of clinical chemistry and clinical neuroscience are given. This provides a convenient method for the concurrent study of the metabolism of three major biogenic amines, and is readily adaptable for studies on cerebrospinal fluid and brain tissue.     

Green chemistry: state of the art through an analysis of the literature

Abstract

The literature of green chemistry has undergone a dramatic increase in the new millennium. Besides that, in ad hoc journals, papers of this type are published in journals of general, organic, and catalytic chemistry. The high proportion of communications within this area indicates that this is a hot topic. These reports mainly concern more environment-friendly synthetic methods, based on better catalytic systems, less harmful solvents and, more rarely, “alternative” physical techniques. Although the compliance with the green chemistry postulates is still partial, a trend in this direction is recognizable. For example, the number of preparative papers that introduce an environmental assessment is rapidly increasing.     

元素周期表与化学教育 ——纪念门捷列夫元素周期表发表150周年

元素周期表的发表是化学知识领域的里程碑,其在化学,尤其是无机化学的学习和研究中的贯穿指导作用和重要性为大家所共识。本文讨论了元素周期表在大学无机化学中的教育作用和开展方式,提出周期表的应用要将化学史与化学教育有机结合。在此基础上,展望周期表未来的发展。     

卟啉及金属卟啉的应用

卟啉和金属卟啉类化合物在仿生化学、催化、太阳能利用、特种材料、医学和分析化学等方面有着越来越重要的作用和应用。本文作一简单介绍。     

Internet上的有机化学软件

综述了Internet上近年来的新的六大类型的有机化学软件的基本内容、特点与网址。     

Atom probe tomography - a high throughput screening tool for atomic scale chemistry

The objective of this paper is to examine the challenges and opportunities in high throughput screening of atomic scale chemistry via a technique known as atom probe tomography. While there are numerous methods that exist in the field of throughput screening, even at the nanoscale, most of the effort is on screening properties , rather than chemistry and/or structure. In this overview, we discuss the role atom probe tomography can have as a high throughput screening tool of atomic scale chemistry. Particular emphasis on the study of organic/ biological materials is given along with the needs and challenges to make atom probe tomography more widespread in the field of combinatorial chemistry.     

超分子中分子间弱要互作用力的研究方法概述

随着超分子化学研究的深入,对分子间弱相互作用力的研究越来越爱到世界科学界的重视,对其本质的研究已成为超分子化学急待解决的问题,本文介绍了超分子体系弱相互作用力的种类及其理论和实验研究方法。