DIRECTED RADIATION SENSITIZERS FROM RH AND PT DIMERS

来自 RH 和 PT 二聚体的定向辐射敏化剂

• 批准号: 3184062
• 负责人: ROBERT C RICHMOND
• 金额: $ 12.57万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184062
• 关键词: ligands; nucleic acid chemical synthesis; pyrimidine dimers; radiation sensitivity; radiopharmacology; radiosensitizer

The intent of this study is to: a) correlated the radiation sensitization by rhodium and platinum dimers in S, typhimurium cells with the range of one and two-electron reduction potentials established by cyclic voltammetry; b) synthesize a family of rhodium and platinum dimers designed to provide a range of one and two electron reduction potentials, and electrochemically characterize the few rhodium and platinum dimers commercially available, for subsequent sensitizer testing; c) determine for selected dimers the sensitizer efficiency as affected by oxygen and specific scavengers of the hydroxyl radical and the hydrated electron. Predictive correlations between sensitizer efficiency and one- and two-electron reduction potentials have been reported. However, the importance of reduction potential as a predictor of metal-induced radiation sensitization has not yet been studied, hence the objectives of this proposed work. The manipulation of reduction potentials within a related family of metal complexes requires carful selection of material. The family of tetracarboxylate- and pyrimidine-bridged rhodium and platinum dimer species is chasen here. Variatin of axial ligands may effect reduction potential by variation of inductive effects upon other complex-ligands containing a combination of sigma- and pi-donating effects. Variation of axial ammine ligands in the Rh2(CH3CO2)4 dimer system witll therefore be explored. Further, the Rh(II) and Pt(II) dimers lend themselves to high valemce manipulations, with expected concomitant variation of reduction potentials. Therefore, Pt(III) dimers, Rh (III) dimers, and mixed Rh(II)/Rh(III) dimers will be synthesized and tested for radiation sensitization. These metal dimers may find use as radiation sensitizers and antitumor drugs in mammalian systems. Ultimately, clinical benefit may be realized for certain of these complexes as combined modality agents interfaced with radiation therapy. The model for this possibility is cisplatin, that was initially shown to be a radiation sensitizer in bacterial systems and is now suggestive in a few clinical cancer trials as enhancing local tumor control when combined with radiation therapy.

本研究的目的是：a）将辐射增敏与辐射增敏相关， 铑和铂二聚体在鼠伤寒沙门氏菌细胞中的作用范围为 单电子和双电子还原电位建立循环 伏安法; B）合成一族铑和铂二聚体， 以提供一个和两个电子还原电位的范围，和 电化学特性的几个铑和铂二聚体 用于随后的敏化剂测试; c）确定 所选二聚体的敏化效率受氧的影响， 羟基自由基和水合电子的特定清除剂。 敏化剂效率与一个和一个之间的预测相关性 已经报道了双电子还原电势。 但 还原电位作为金属感生辐射预测因子重要性 敏感性尚未研究，因此，这一目标 提议的工作。 还原电位的操作在一个相关的 金属配合物家族需要仔细选择材料。 的 四羧酸和嘧啶桥连的铑和铂族 二聚体在这里是chasen。 轴向配体变化可能影响 通过对其他物质的感应作用的变化而产生的还原电位 含有σ-和π-供体的组合的络合配体 方面的影响. Rh_2（CH_3CO_2）_4二聚体中轴向氨配体的变化 因此，将对系统进行探索。 此外，Rh（II）和Pt（II）二聚体 使他们能够进行高价值的操纵，并预期伴随着 还原电位的变化。 因此，Pt（III）二聚体、Rh（III） 二聚体和混合Rh（II）/Rh（III）二聚体将被合成并测试 辐射敏化 这些金属二聚体可用作辐射增敏剂和抗肿瘤剂。 哺乳动物系统中的药物。 最终，可实现临床获益 对于某些作为联合方式试剂的这些复合物， 放射治疗 这种可能性的模型是顺铂， 最初显示为细菌系统中的辐射敏化剂， 现在在一些临床癌症试验中提示， 与放射治疗相结合。