Trithiolato-bridged dinuclear ruthenium(II) complexes [Ru₂(p-cym)₂(SR)₃]Cl (p-cym = p-cymene, R = benzyl derivatives) are regarded as the most cytotoxically potent metal(II) arene antineoplastics, but are oftentimes limited by their poor solubility in aqueous media. Thus, we designed bisphosphonate-functionalized ligands for use in a modular two-step complexation process to synthesize six trithiolato-bridged dinuclear ruthenium(II) and osmium(II) arene complexes bearing one to three bisphosphonate-benzylmercaptane derived ligands. In addition to improved aqueous solubility the high affinity of bisphosphonates towards apatite structures found in bone and bone metastases may grant selective targeting properties to functionalized organometallics. The complex stabilities and hydroxyapatite binding behavior were determined by UV/Vis spectroscopy. The bisphosphonate functionalization decreases antiproliferative activity in vitro, which was correlated to lower cellular accumulation, due to the different lipophilic profiles of the drug candidates.

三硫醇桥联双核钌 (II) 配合物 [Ru ₂ ( p -cym) ₂ (SR) ₃ ]Cl ( p -cym =  p- 伞花烃，R = 苄基衍生物）被认为是最具细胞毒性的金属 (II) 芳烃抗肿瘤剂，但通常因其在水性介质中的溶解度差而受到限制。因此，我们设计了用于模块化两步络合过程的双膦酸盐官能化配体，以合成六种三硫醇桥联的双核钌 (II) 和锇 (II) 芳烃配合物，这些配合物带有一到三个双膦酸盐-苄硫醇衍生的配体。除了提高水溶性外，双膦酸盐对骨和骨转移中发现的磷灰石结构的高亲和力可以赋予功能化有机金属选择性靶向特性。复合物稳定性和羟基磷灰石结合行为通过紫外/可见光谱测定。双膦酸盐官能化降低抗增殖活性由于候选药物的亲脂性不同，这与较低的细胞积累有关。