The coordination chemistry and anticancer activity of organo-ruthenium(<scp>ii</scp>), -iridium(<scp>iii</scp>) and -rhodium(<scp>iii</scp>) 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 <i>p</i>-TolSO₂NHC(S)NHPh, EtSO₂NHC(S)NHPh and CH₃SO₂NHC(S)NHPh and [(η⁶-<i>p</i>-cymene)RuCl₂]₂, [(η⁶-arene)RuCl₂(PR₃)] (arene = benzene or <i>p</i>-cymene), [Cp*MCl₂(PR₃)] or [Cp*RhCl₂]₂ (M = Ir(III), Rh(III)), Cp* = η⁵-pentamethylcyclopentadienyl, PR₃ = triphenylphosphine (PPh₃), 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, <i>i.e.</i>, <i>proximal</i> (coordination <i>via</i> S,N_(sulfonated) placing the sulfonyl group near the coordination sphere) or <i>distal</i> (coordination <i>via</i> S,N_{(non-sulfonated)}, placing the sulfonyl group away from the coordination sphere), is directly related to the steric bulk around the metal centre. <i>Proximal</i> to <i>distal</i> isomerisation of the complex [(η⁶-<i>p</i>-cymene)Ru{<i>p</i>-TolSO₂NC(S)N(PPh₃)}] (1aL1) was observed by ¹H and ³¹P{¹H} 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 <i>in vitro</i> 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) <i>p</i>-cymene complexes.