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(η6-C6H5(CH2)3OH)(XY)Cl]+/0 (1-13) bearing the hemilabile η6-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(η6-arene-O-κ1)(XY)] n+. Complexes 1C-13C of formula [Os(η6:κ1-C6H5(CH2)3OH/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.