Here, we report our initial investigations into the coordination chemistry of symmetric diacylated thiourea ligands ((RCONH)2CS) (R = Me, Et or Ph) acting as both mono and dianionic ligands with platinum(II), palladium(II) and gold(III) metal centres. Initial investigations were centred on mixed ligand bis(triphenylphosphine) (PPh3) complexes which were prepared by reactions between cis-[PtCl2(PPh3)2] and (RCONH)2CS. A subsequent series of mixed ligand complexes from the diethyl-diacylthiourea ligand ((CH2CH2CONH)2CS) with [PtCl2(dppe)] (dppe = Ph2PCH2CH2PPh2), [PdCl2(phen)] (phen = 1,10-phenanthroline), [AuCl2(anp)] (anp = cyclometallated 2-anilinopyridyl) and [PtCl2(COD)] (COD = 1,5-cyclooctadiene) were also prepared. The complexes were characterized by a combination of common techniques (MS, NMR and SC-XRD) which determined that the ligands coordinated to the metal centres in an unexpected S,N bidentate chelate manner in all instances. The complexes showed a small degree of aqueous instability as a result of hydrolysis. Computational techniques (NCI, EDA and HS) were used to analyse complexes whose solid state structure was able to be determined crystallographically. The presence of a chalcogen bond between the thiourea sulfur and acyl oxygen atoms was revealed which dominates the molecular structure. The cyclometallated 2-anilinopyridyl gold(III) complex 1f demonstrates intermolecular dimerism in the solid state. Hirshfeld surface analysis was used to determine the percentage contribution of inherent intermolecular interactions to crystal packing and the specific contacts responsible for spatial orientations in 1a, 1b, and 1f.

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 p-TolSO2NHC(S)NHPh, EtSO2NHC(S)NHPh and CH3SO2NHC(S)NHPh and [(eta 6-p-cymene)RuCl2]2, [(eta 6-arene)RuCl2(PR3)] (arene = benzene or p-cymene), [Cp*MCl2(PR3)] or [Cp*RhCl2]2 (M = Ir(iii), Rh(iii)), Cp* = eta 5-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.e., proximal (coordination via S,N(sulfonated) placing the sulfonyl group near the coordination sphere) or distal (coordination via S,N(non-sulfonated), placing the sulfonyl group away from the coordination sphere), is directly related to the steric bulk around the metal centre. Proximal to distal isomerisation of the complex [(eta 6-p-cymene)Ru{p-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 in vitro 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) p-cymene complexes.

A series of sulfonyl-substituted thiourea platinum(II) complexes bearing ancillary phosphine ligands were prepared by the reaction between cis-[PtCl2(PR3)2] (PR3 = triphenylphosphine, tris(2-cyanoethyl)phosphine and 1,3,5-triaza-7-phosphaadamantane) and either p-TolSO2NHC(S)NHPh or EtSO2NHC(S)NHPh, in a refluxing Et3N/methanol mixture. The mixed ligand complexes, bearing a single phosphine and pyridine, were also prepared by the reactions between cis-[PtCl2(COD)] (COD = cyclooctadiene), pyridine and p-TolSO2NHC(S)NHPh or EtSO2NHC(S)NHPh. For each complex, the thiourea ligand binds as a dianion through the S and NPh groups in the distal isomer with a remote NSO2R group. Only in the case of the reaction between the complex [PtCl2(PPh3)2] and TolSO2NHC(S)NHCH(CH3)3) was the proximal isomer formed on account of the bulky t-butyl substituent on the thiourea. X-ray structures and computational analysis revealed another reason for this preferential distal isomer formation is most likely due to the presence of a stabilising chalcogen bond, which is otherwise unavailable in the proximal isomer.

Reactions between the phosphorylthiourea ligands (EtO)2PONHC(S)NHPh (L1), (EtO)2PONHC(S)NHCH(CH3)3) (L2) and (EtO)2PONHC(S)NHCH2CH3 (L3) and cis-[PtCl2(PPh3)2] gave complexes in which the ligands bind to the platinum(II) centre as dianionic ligands. For ligands L1 and L3, the ligand binds through the thiourea sulfur and the N-alkyl nitrogen atoms, giving the distal isomer. In contrast, the ligand L2, on account of the bulky t-butyl substituent on the ligand, coordinates via the sulfur and N-phosphoryl nitrogen atoms, giving the proximal isomer. The identities of the isomers were confirmed by single crystal X-ray analysis and 31P{1H} NMR spectroscopy. The latter showing that the appearance or absence of 3J(PP) couplings between the ligand and ancillary ligands provides indicative isomeric information. Further reactions between the ligand L1 and a series of bis-phosphine, triphenylarsine and triphenylstibine platinum(II) starting complexes gave the corresponding products also as the distal linkage isomer. Computational analysis reveals a possible chalcogen bond non-covalent interaction that may be responsible for the preference for the distal isomer.

Reactions of the complexes cis-[PtCl2(PPh3)(2)], [PtCl2(dppp)] (dppp = Ph2P(CH2)(3)PPh2), [MCl2(dppe)] (dppe = Ph2P(CH2)(2)PPh2, M = Ni, Pd), [PdCl2(bipy)] (bipy = 2,2' -bipyridine) and [AuCl2(bp)] (bp = cyclometallated 2-benzylpyridine) with p-TolSO(2)NHC(S)NHPh and Et3N in refluxing methanol gave a series of new thiourea complexes containing the ligand bound as a dianion through the S and the NPh groups. The related thioureas RSO2NHC(S)NHPh (R = Me, Et) and p-TolSO(2)NHC(S)NHCH2CH=CH2 were also reacted with cis-[PtCl2(PPh3)(2)] to form the corresponding complexes [Pt{RSO2NC(S)NPh}(PPh3)(2)] and [Pt{TolSO(2)NC(S)NCH2CH=CH2} (PPh3)(2)] respectively. X-ray structure determinations were carried out on the thiourea MeSO2NHC(S)NHPh and its platinum complex [Pt{MeSO2NC(S)NPh}(PPh3)2], as well as [Pt{TolSO(2)NC(S)NPh}(PPh3)(2)]. Both complexes form the distal isomer with a remote NSO2R group, and no evidence was observed for isomerisation of these platinum complexes in solution. The palladium complexes [Pd{TolSO(2)NC(S)NPh}L-2] [L-2 = Ph2PCH2CH2PPh2 (dppe), or 2,2'-bipyridine (bipy)] undergo decomposition in solution to form the sulfide-bridged aggregates [Pd3S2(L-2)(3)](2+), identified by ESI MS and P-31 NMR.