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.
