The coordination chemistry and anticancer activity of organo-ruthenium(II), -iridium(III) and -rhodium(III) complexes with sulfonyl-substituted thiourea ligands

Some half-sandwich compounds with a variety of ligands and metal centres have shown promising anticancer activity. Herein we report a series of reactions between the sulfonylthiourea ligands -TolSO NHC(S)NHPh, EtSO NHC(S)NHPh and CH SO NHC(S)NHPh and [(η - -cymene)RuCl ] , [(η -arene)RuCl (PR )] (arene = benzene or -cymene), [Cp*MCl (PR )] or [Cp*RhCl ] (M = Ir(III), Rh(III)), Cp* = η -pentamethylcyclopentadienyl, PR = triphenylphosphine (PPh ), tris(2-cyanoethyl)phosphine (tcep) and 1,3,5-triaza-7-phosphaadamantane (pta) and their corresponding piano stool complexes. Single crystal X-ray diffraction structure determinations indicated that the resulting linkage isomer of the complex, , (coordination S,N placing the sulfonyl group near the coordination sphere) or (coordination S,N , placing the sulfonyl group away from the coordination sphere), is directly related to the steric bulk around the metal centre. to isomerisation of the complex [(η - -cymene)Ru{ -TolSO NC(S)N(PPh )}] (1aL1) was observed by H and P{ H} NMR spectroscopy. DFT calculations suggested this to be the result of the conversion from the initially formed kinetically favourable to the thermodynamically favourable isomer. Computational investigation of non-covalent interactions using the reduced density gradient also revealed a chalcogen bond present between the thiourea sulfur and sulfonyl oxygen atoms of complex 1aLa. The antiproliferative activity of several complexes was determined against human cancer cells, which revealed a correlation between potency and lipophilic properties of the ancillary ligands for a series of Ru(II) -cymene complexes.