STRUCTURAL STUDIES OF RHODIUM(II)-ACETATE COMPLEXES WITH CYSTEINE AND ITS DERIVA

乙酸铑(II)-半胱氨酸及其衍生物配合物的结构研究

• 批准号: 8170260
• 负责人: FARIDEH JALILEHVAND
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170260
• 关键词: Acetates; Amino Acids; Binding; Carbon Dioxide; Cisplatin; Complex; Computer Retrieval of Information on Scientific Projects Database; Cysteine; DNA; DNA biosynthesis; DNA-Directed DNA Polymerase; Enzymes; Funding; Grant; Institution; Ions; Lead; Ligands; Metals; Methods; Nucleotides; Penicillamine; Proteins; Reaction; Relative (related person); Replication-Associated Process; Research; Research Personnel; Resources; Rhodium; Source; Structure; Sulfhydryl Compounds; Toxic effect; United States National Institutes of Health; base; carboxylate; mecysteine; prevent; solid state

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The antitumor activity of rhodium(II) carboxylates, [Rh2(RCOO)4], was discovered in 1976; however, its rather high toxicity relative to cisplatin, Pt(NH3)2Cl2, has prevented it from becoming clinically approved. This class of dirhodium(II) compounds can interact with both DNA and proteins: they can form complexes with the DNA nucleotide bases, interrupting the DNA replication process, or bind to the amino acid residues of proteins. Earlier studies suggest that reaction of rhodium(II) carboxylates with free thiol (-SH) containing groups, such as aminoacid cysteine, results in decomposition of the dirhodium complex, breaking the Rh-Rh bond and releasing CO2. It has been proposed that such a reaction with free thiol group(s) at or near the active center of an enzyme, such as DNA polymerase, can lead to inactivation of the enzyme; this view is in parallel with the toxicity effects of the rhodium(II) carboxylates. Pnematikakis et al. investigated complexes formed between rhodium(II) acetate, [Rh2(CH3COO)4], with L-cysteine, cysteine methyl-ester and D- penicillamine (3,3'-dimethyl cysteine) in the solid state, using IR and EPR spectroscopic methods, and concluded that these ligands form (N,S)- bound monomeric Rh(II) complexes. However, no details about the local structure around Rh(II) ions in these complexes, i.e. metal-ligand bond distances, is available.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 1976 年发现了羧酸铑 (II) [Rh2(RCOO)4] 的抗肿瘤活性；然而，其相对于顺铂 Pt(NH3)2Cl2 的较高毒性使其无法获得临床批准。这类二铑(II)化合物可以与DNA和蛋白质相互作用：它们可以与DNA核苷酸碱基形成复合物，中断DNA复制过程，或者与蛋白质的氨基酸残基结合。早期研究表明，羧酸铑 (II) 与含有游离硫醇 (-SH) 的基团（例如氨基酸半胱氨酸）反应会导致二铑络合物分解，破坏 Rh-Rh 键并释放 CO2。已经提出，在酶（例如DNA聚合酶）的活性中心处或附近与游离硫醇基团的这种反应可以导致酶失活；这一观点与羧酸铑(II)的毒性作用是一致的。 普内马蒂卡基斯等人。使用红外和 EPR 光谱研究了醋酸铑 (II)、[Rh2(CH3COO)4] 与固态 L-半胱氨酸、半胱氨酸甲酯和 D-青霉胺（3,3'-二甲基半胱氨酸）之间形成的络合物方法，并得出结论，这些配体形成 (N,S)-结合的单体 Rh(II) 配合物。然而，没有关于这些配合物中 Rh(II) 离子周围局部结构的详细信息，即金属-配体键距。