Osmium(II) and ruthenium(II) arene maltolato complexes: Rapid hydrolysis and nucleobase binding

Density functional calculations show that aquation of [Os(eta(6)-arene)(XY)Cl](n+) complexes is more facile for complexes in which XY=an anionic O,O-chelated ligand compared to a neutral N,N-chelated ligand, and the mechanism more dissociative in character. The O,O-chelated XY=maltolato (mal) [M(eta(6)-p-cym)(mal)Cl] complexes, in which p-cvm=p-cymene, M=Os-II (1) and Run (2). were synthesised and the X-ray crystal structures of I and 2-2H(2)O determined. Their hydrolysis rates were rapid (too fast to follow by NMR spectroscopy). The aqua adduct of the Os-II complex 1 was 1.6 pK(a) units more acidic than that of the Ru-II complex 2. Dynamic NMR studies suggested that O,O-chelate ring opening occurs on a millisecond timescale in coordinating proton-donor solvents, and loss of chelated mal in aqueous solution led to the formation of the hydroxo-bridged dimers [(eta(6)-p-cyrn)M(mu-OH)(3)M(eta(6)-p-cym)](+). ne proportion of this dimer in solutions of the Os-II complex 1 increased with dilution and it predominated at micromolar concentrations, even in the presence of 0.1 M NaCl (conditions close to those used for cytotoxicity testing). Although 9-ethylguanine (9-EtG) binds rapidly to Os-II in 1 and more strongly (log K=4.4) than to Ru-II in 2 (log K=3.9), the Os-II adduct [Os(eta(6)-p-cym)(mal)-(9EtG)](+) was unstable with respect to formation of the hydroxo-bridged dimer at micromolar concentrations. Such insights into the aqueous solution chemistry of metal-arene complexes under biologically relevant conditions will aid the rational design of organometallic anticancer agents.