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-CH(CH)OH)(XY)Cl] () bearing the hemilabile η-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-arene--κ)(XY)] . Complexes of formula [Os(η:κ-CH(CH)OH/O)(XY)] are fully characterised, including the X-ray structure of cation . Tether-ring formation is reversible and pH dependent. Osmium complexes bearing picolinate N,O-chelates () catalyse the hydrogenation of pyruvate to lactate. Intracellular lactate production upon co-incubation of complex (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.