摘要
尽管含量甚微,铜以不同的浓度和化学形态广泛存在于地球地壳、地表、深水甚至空气中。铜是最先被人类使用的金属之一,最早的文物可追溯到一万年前。现在,世界的精铜产量每年超过了一万六千吨。铜是生命必需微量元素,主要是因为它的氧化还原灵敏性,能够作为许多酶的必需辅助因子,如细胞色素c氧化酶和超氧(化)物歧化酶。在某些动物中(如章鱼、蜗牛、蜘蛛、牡蛎)铜-血蓝蛋白代替血红蛋白起到氧气运输的功能。但是,当铜在身体或组织过量存在,这些氧化还原活性也使Cu+/Cu2+离子对成为活性氧簇形成的强效催化剂。在铜过载或中毒的情况下,螯合疗法是一种治疗手段。不同的化学分子已经作为螯合剂被临床应用,或正在临床实验或研究当中。值得注意的是,螯合疗法也被建议用于治疗一些神经退行性疾病或心血管疾病。这个综述在简明介绍铜的动态平衡和某些稳态失衡的案例后,对主要的螯合剂(正在用的或有潜力的)进行了描述;对其在溶液中、甚至在金属或配体竞争剂存在的情况下及生理条件下的化学性质进行了讨论。同时概述了西方主要国家法律对螯合剂使用及铜在食品、药物、化妆品中的限度规范。
关键词: 双功能配体,铜螯合剂,铜代谢,铜超载,神经退行性疾病,青霉胺,钼酸盐,曲恩汀
Current Medicinal Chemistry
Title:Copper Chelators: Chemical Properties and Bio-medical Applications
Volume: 21 Issue: 33
Author(s): M. Tegoni, D. Valensin, L. Toso and M. Remelli
Affiliation:
关键词: 双功能配体,铜螯合剂,铜代谢,铜超载,神经退行性疾病,青霉胺,钼酸盐,曲恩汀
摘要: Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons / year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu+/Cu2+ a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined.
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Cite this article as:
Tegoni M., Valensin D., Toso L. and Remelli M., Copper Chelators: Chemical Properties and Bio-medical Applications, Current Medicinal Chemistry 2014; 21 (33) . https://dx.doi.org/10.2174/0929867321666140601161939
DOI https://dx.doi.org/10.2174/0929867321666140601161939 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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