In this work, two thiourea ligands bearing a phosphine group in one arm and in the other a phenyl group (T2) or 3,5-di-CF3 substituted phenyl ring (T1) have been prepared and their coordination to Au and Ag has been studied. A different behavior is observed for gold complexes, a linear geometry with coordination only to the phosphorus atom or an equilibrium between the linear and three-coordinated species is present, whereas for silver complexes the coordination of the ligand as P^S chelate is found. The thiourea ligands and their complexes were explored against different cancer cell lines (HeLa, A549, and Jurkat). The thiourea ligands do not exhibit relevant cytotoxicity in the tested cell lines and the coordination of a metal triggers excellent cytotoxic values in all cases. In general, data showed that gold complexes are more cytotoxic than the silver compounds with T1, in particular the complexes [AuT1(PPh3)]OTf, the bis(thiourea) [Au(T1)2]OTf and the gold-thiolate species [Au(SR)T1]. In contrast, with T2 better results are obtained with silver species [AgT1(PPh3)]OTf and the [Ag(T1)2]OTf. The role played by the ancillary ligand bound to the metal is important since it strongly affects the cytotoxic activity, being the bis(thiourea) complex the most active species. This study demonstrates that metal complexes derived from thiourea can be biologically active and these compounds are promising leads for further development as potential anticancer agents.

This work represents the first example of a gold-catalyzed formation of 1,3-thiazine/1,3-thiazinane by means of a catalytic approach and further uncommon isolation of the two tautomers. The developed protocol gives rise to a broad scope of 1,3-thiazine derivatives with excellent yields in short reaction times. Interestingly, different isomers could be obtained depending on the state of the compound, and in the crystal state the 1,3-thiazinane isomer is obtained, while in solution the 1,3-thiazine is the unique isomer. This work represents an interesting approach for the synthesis of potential biologically relevant molecules and a crucial precedent in tautomerism isolation and characterization.