Influence of the Spacer Length on the <i>in Vitro</i> Anticancer Activity of Dinuclear Ruthenium−Arene Compounds

Water-soluble dinuclear Ru−arene complexes were synthesized and found to exert promising cytotoxic effects in human cancer cells, which could be increased to an IC50 of 0.29 μM by increasing the spacer length between the metal centers. Cytotoxicity could be correlated with lipophilicity (log P values) and water solubility. The most potent dinuclear compound, 1,12-bis{chlorido[3-(oxo-κO)-2-methyl-4-pyridinonato-κO4](η6-p-isopropyltoluene)ruthenium}dodecane, is at least 2−3 orders of magnitude more active than the mononuclear analogue chlorido[3-(oxo-κO)-2-methyl-4-pyronato-κO4](η6-p-isopropyltoluene)ruthenium.水溶性双核钌-芳烃配合物经合成后被发现对人类癌细胞具有可观的细胞毒活性；通过增大金属中心间的间隔臂长度，其半最大效应浓度（IC50）可低至0.29 μM。该细胞毒活性与其亲脂性（log P值）及水溶性密切相关。活性最强的双核配合物为1,12-双{氯代[3-(氧代-κO)-2-甲基-4-吡啶酮合-κO4](η⁶-对异丙基甲苯)钌}十二烷，其活性较单核类似物氯代[3-(氧代-κO)-2-甲基-4-吡喃酮合-κO4](η⁶-对异丙基甲苯)钌至少高出2~3个数量级。