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(eta(6)-C6H5(CH2)(3)OH)(XY)Cl](+/0) (1-13) bearing the hemilabile eta(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(eta(6)-arene-O-kappa(1))(XY)](n+). Complexes 1C-13C of formula [Os(eta(6):kappa(1)-C6H5(CH2)(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.