Transfer hydrogenation catalysis in cells

Hydrogenation reactions in biology are usually carried out by enzymes with nicotinamide adenine dinucleotide (NAD(P)H) or flavin mononucleotide (FAMH(2))/flavinadenine dinucleotide (FADH(2)) as cofactors and hydride sources. Industrial scale chemical transfer hydrogenation uses small molecules such as formic acid or alcohols (e.g. propanol) as hydride sources and transition metal complexes as catalysts. We focus here on organometallic half-sandwich Ru(II) and Os(II) η(6)–arene complexes and Rh(III) and Ir(III) η(5)–Cp(x) complexes which catalyse hydrogenation of biomolecules such as pyruvate and quinones in aqueous media, and generate biologically important species such as H(2) and H(2)O(2). Organometallic catalysts can achieve enantioselectivity, and moreover can be active in living cells, which is surprising on account of the variety of poisons present. Such catalysts can induce reductive stress using formate as hydride source or oxidative stress by accepting hydride from NAD(P)H. In some cases, photocatalytic redox reactions can be induced by light absorption at metal or flavin centres. These artificial transformations can interfere in biochemical pathways in unusual ways, and are the basis for the design of metallodrugs with novel mechanisms of action.