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

Abstract

Density functional calculations show that aquation of [Os(η 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(η6-p-cym)(mal)Cl] complexes, in which p-cym=p-cymenc, M = OsII (1) and RuII (2), were synthesised and the X-ray crystal structures of 1 and 2·2 H2O determined. Their hydrolysis rates were rapid (too fast to follow by NMR spectroscopy). The aqua adduct of the OsII complex 1 was 1.6 pK a units more acidic than that of the RuII 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 [(η6-p-cym)M(μ-OH)3M(η6-p- cym)]+. The 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 OsII in 1 and more strongly (log K = 4.4) than to Ru II in 2 (log K = 3.9), the OsII adduct [Os(η6-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. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.