Organometallic complexes have the potential to behave as catalytic drugs. We investigate here Rh(III) complexes of general formula [(Cp(x))Rh(N,N')(Cl)], where N,N' is
ethylenediamine (en),
2,2'-bipyridine (bpy),
1,10-phenanthroline (phen) or N-(2-aminoethyl)-4-(trifluoromethyl)benzenesulfonamide (TfEn), and Cp(x) is pentamethylcyclopentadienyl (Cp*), 1-phenyl-2,3,4,5-tetramethylcyclopentadienyl (Cp(xPh)) or 1-biphenyl-2,3,4,5-tetramethyl cyclopentadienyl (Cp(xPhPh)). These complexes can reduce
NAD(+) to
NADH using
formate as a hydride source under biologically-relevant conditions. The catalytic activity decreased in the order of N,N-chelated
ligand bpy > phen > en with Cp* as the η(5)-donor. The en complexes (1-3) became more active with extension to the Cp(X) ring, whereas the activity of the phen (7-9) and bpy (4-6) compounds decreased. [Cp*Rh(bpy)Cl](+) (4) showed the highest catalytic activity, with a TOF of 37.4±2h(-1). Fast hydrolysis of the chlorido complexes 1-10 was observed by (1)H NMR (<10min at 310K). The pKa* values for the aqua adducts were determined to be ca. 8-10. Complexes 1-9 also catalysed the reduction of
pyruvate to
lactate using
formate as the hydride donor. The efficiency of the transfer hydrogenation reactions was highly dependent on the nature of the chelating
ligand and the Cp(x) ring. Competition reactions between
NAD(+) and
pyruvate for reduction by
formate catalysed by 4 showed a preference for reduction of
NAD(+). The antiproliferative activity of complex 3 towards A2780 human
ovarian cancer cells increased by up to 50% when administered in combination with non-toxic doses of
formate, suggesting that transfer hydrogenation can induce reductive stress in
cancer cells.