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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 1976年发现了仇恨（II）羧酸盐[RH2（RCOO）4]的抗肿瘤活性。但是，相对于顺铂（NH3）2cl2，其毒性相当高，使其无法获得临床认可。这类dirhodium（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，或与蛋白质的氨基酸残基结合。较早的研究表明，硫酸烷基盐与含有氨基酸半胱氨酸等游离硫醇（-SH）的反应导致dirhodium络合物的分解，破坏RH-RH键并释放CO2。已经提出，与酶的活性中心或附近的自由硫醇基（例如DNA聚合酶）的这种反应可导致酶失活。这种观点与铑（II）羧酸盐的毒性作用平行。 Pnematikakis等。研究的复合物（II）乙酸菜（II）[RH2（CH3COO）4]与L-半胱氨酸，半胱氨酸甲基酯和D-青霉素（3,3'-二甲基半胱氨酸）之间形成，使用IR和EPR光谱方法，使用IR和EPR光谱方法，并结束了这些复合物（ii）的结论（ii）（ii）（ii）。但是，没有有关这些复合物中RH（II）离子（即金属配体键距离）周围局部结构的细节。