Osmium(ii) tethered half-sandwich complexes: pH-dependent aqueous speciation and transfer hydrogenation in cells.

Aquation is often acknowledged as a necessary step for metallodrug activity inside the cell. Hemilabile ligands can be used for reversible metallodrug activation. We report a new family of osmium(ii) arene complexes of formula [Os(η(6)-C(6)H(5)(CH(2))(3)OH)(XY)Cl](+/0) (1-13) bearing the hemilabile η(6)-bound arene 3-phenylpropanol, where XY is a neutral N,N or an anionic N,O(-) bidentate chelating ligand. Os-Cl bond cleavage in water leads to the formation of the hydroxido/aqua adduct, Os-OH(H). In spite of being considered inert, the hydroxido adduct unexpectedly triggers rapid tether ring formation by attachment of the pendant alcohol-oxygen to the osmium centre, resulting in the alkoxy tethered complex [Os(η(6)-arene-O-κ(1))(XY)] (n+). Complexes 1C-13C of formula [Os(η(6):κ(1)-C(6)H(5)(CH(2))(3)OH/O)(XY)](+) are fully characterised, including the X-ray structure of cation 3C. Tether-ring formation is reversible and pH dependent. Osmium complexes bearing picolinate N,O-chelates (9-12) catalyse the hydrogenation of pyruvate to lactate. Intracellular lactate production upon co-incubation of complex 11 (XY = 4-Me-picolinate) with formate has been quantified inside MDA-MB-231 and MCF7 breast cancer cells. The tether Os-arene complexes presented here can be exploited for the intracellular conversion of metabolites that are essential in the intricate metabolism of the cancer cell.