DIRECTED RADIATION SENSITIZERS FORM RH AND PT DIMERS

这项研究的目的是：a)关联辐射敏化 通过在S中加入Rg和铂二聚体，鼠伤寒杆菌细胞的范围 由循环建立的单电子和双电子还原势 伏安法；b)合成一系列设计的铑和铂二聚体 以提供一个和两个电子还原电势的范围，以及 为数不多的铑和铂二聚体的电化学表征 商业上可用的，用于随后的敏化剂测试；c)确定 所选二聚体的增感效率受氧气和 羟基自由基和水合电子的特定清除剂。 敏化剂效率与一次和一次之间的预测相关性 已有双电子还原电势的报道。然而， 还原电位作为金属辐射预测指标的重要性 敏化作用尚未被研究，因此本研究的目标是 建议的工作。在一个相关的系统中对还原电位的处理 金属络合物家族需要谨慎选择材料。这个 四羧酸盐和嘧啶桥联的Rh和Plt家族 二聚体物种在这里是Chasen。轴向配体的变化可能会影响 通过对其他生物的诱导效应的变化而产生的还原潜力 络合物--含有Sigma-和pi-给体组合的配体 效果。Rh2(CH3CO2)4二聚体中轴胺配体的变化 因此，将对系统进行探索。此外，Rh(II)和Pt(II)二聚体 倾向于高价操纵，预计会伴随而来 还原电位的变化。因此，铂(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药物。 哺乳动物体内的药物。最终，临床益处可能会实现。 对于这些复合体中的某些作为组合的通道代理与 放射疗法。这种可能性的模型是顺铂，也就是 最初被证明是细菌系统中的辐射敏感剂，并且 现在在一些临床癌症试验中建议增强局部肿瘤 当与放射治疗相结合时，控制。

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.