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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 研究中心，而研究中心不一定是研究者所在的机构。 铑（II）羧酸盐[Rh 2（RCOO）4]的抗肿瘤活性于1976年发现;然而，其相对于顺铂Pt（NH3）2Cl 2的相当高的毒性使其无法获得临床批准。这类二铑化合物可以与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。早期的研究表明，铑（II）羧酸盐与游离巯基（-SH）的反应，如氨基酸半胱氨酸，导致二铑络合物的分解，破坏Rh-Rh键并释放CO2。有人提出，在酶（如DNA聚合酶）的活性中心处或附近与游离巯基的反应可导致酶失活;这种观点与羧酸铑（II）的毒性效应平行。 Pnematikakis等人使用IR和EPR光谱方法研究了固态下乙酸铑（II）[Rh 2（CH 3COO）4]与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，并得出结论，这些配体形成（N，S）结合的单体Rh（II）络合物。然而，没有关于这些络合物中Rh（II）离子周围的局部结构的细节，即金属-配体键距。

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.