Hydrogen Bonding and Anticancer Properties of Water-Soluble Chiral p-Cymene Ru^II Compounds with Amino-Oxime Ligands

An investigation into the effects of hydrogen bonding on the aggregation tendency of ruthenium compounds [(η6-p-cymene)Ru(κNHR,κNOH)Cl]Cl {R = Ph (1a), Bn (1b)} and [(η6-p-cymene)Ru(κ2NH(2-pic),κNOH)][PF6]2 (1c), [(η6-p-cymene)Ru(κNHBn,κNO)Cl] (2b), and [(η6-p-cymene)Ru(κNBn,κ2NO)] (3b) has been performed by means of concentration-dependence 1H NMR chemical shift and DOSY experiments. The synthesis and full characterization of new compounds 1c, [(η6-p-cymene)Ru(κNPh,κ2NO)] (3a) and 3b are also reported. The effect of the water-soluble ruthenium complexes 1a-c on cytotoxicity, cell adhesion, and cell migration of the androgen-independent prostate cancer PC3 cells have been assessed by MTT, adhesion to type-I-collagen, and recovery of monolayer wounds assays, respectively. Interactions of 1a-c with DNA and human serum albumin have also been studied. Together, the properties reported herein suggest that ruthenium compounds 1a-c have considerable potential as anticancer agents against advanced prostate cancer. The ability of water-soluble, chiral arene RuII compounds with amino-oxime ligands to aggregate in solution by means of hydrogen bonding is described. The compounds do not interact with plasmid (pBR322) DNA but display strong cytotoxic and antimetastatic effects in vitro against androgen-unresponsive human prostate cancer PC3 cell line.