Catalytic anticancer metallodrugs active at low doses could minimize side-effects, introduce novel mechanisms of action that combat resistance and widen the spectrum of anticancer-drug activity. Here we use highly stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, [Os(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to achieve a highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways. Reduction is shown both in aqueous model systems and in human cancer cells, with non-toxic concentrations of sodium formate used as a hydride source. The catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to overexpress a deformylase enzyme. Transfer-hydrogenation catalysts that generate reductive stress in cancer cells offer a new approach to cancer therapy.

低剂量活性的催化抗癌金属药物可以最大限度地减少副作用，引入对抗耐药性的新作用机制并扩大抗癌药物活性的范围。在这里，我们使用高度稳定的手性半夹心有机金属 Os( II ) 芳烃磺酰二胺配合物，[Os(arene)(TsDPEN)] (TsDPEN, N -( p-甲苯磺酰基）-1,2-二苯基乙二胺），以实现丙酮酸的高度对映选择性还原，丙酮酸是代谢途径中的关键中间体。在水性模型系统和人类癌细胞中都显示出还原，其中无毒浓度的甲酸钠用作氢化物源。催化机制产生对卵巢癌细胞与非癌性成纤维细胞（卵巢和肺）的选择性，后者通常用作健康增殖细胞的模型。甲酸前体N-甲酰甲硫氨酸被探索为 PC3 前列腺癌细胞中甲酸的替代物，已知其过表达去甲酰基酶。在癌细胞中产生还原性应力的转移氢化催化剂为癌症治疗提供了一种新方法。