Structure and solution biospeciation on tricarbonylrhenium(I) complexes of mercaptopyrimidines with multifaceted biological activity.

In this study, we report the synthesis and detailed characterization of four novel bidentate (N, N) ligands incorporating a 2-(methylthio)pyrimidine moiety and their fac-tricarbonylrhenium(I) complexes (ReB1-ReB4 and ReB1Aq) with the general formula fac-[Re(CO)3(N,N)X]n+, with X = Cl- or H2O and n = 0 or 1. Designed to integrate biologically relevant functionalities, these complexes exhibited promising multifunctional bioactivity. Cytotoxicity assays demonstrated moderate activity (IC50 = 11-78 µM) on various human cancer cell lines, with certain derivatives showing notable selectivity toward the Colo205 line. Most of the chlorido complexes effectively inhibited the replication of Herpes simplex virus type 2, while ReB4 displayed significant antibacterial activity against Staphylococcus aureus, including methicillin-resistant strains (MIC = 12.5-25 µM), and demonstrated biofilm inhibition. Aqueous stability of these organometallic complexes was thoroughly investigated, and complexes ReB2 and ReB3 containing a pyrimidine and a thiazole ring, respectively, gradually decompose in aqueous media, correlating with a decline in anticancer activity. Ligand-exchange processes were observed, in which the chlorido co-ligands were replaced by water, thus affecting the solubility and lipophilicity. The aqua complex ReB1Aq exhibited a low chloride affinity, and the pKa of the coordinated water molecule was obtained to be ∼8. Its interaction with human serum albumin was investigated in detail and was found to be dominated by non-covalent interactions, indicating that no coordination bond formation occurs with the protein.