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(η^6^‐p‐cym)(mal)Cl] complexes, in which p‐cym=p‐cymene, M=Os^II^ (1) and Ru^II^ (2), were synthesised and the X‐ray crystal structures of 1 and **2⋅**2 H~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 p__K__~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 [(η^6^‐p‐cym)M(μ‐OH)~3~M(η^6^‐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 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(η^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.