Synthesis of a <i>fac</i>-Tricarbonylrhenium(I) Complex with Pyrithione, Its Physicochemical Characterization, and Assessment of Biological Effects

Research on rhenium complexes containing <i>fac</i>-tricarbonyl fragments has been on the rise in recent decades. Some complexes of this type exhibit advantageous properties that can be utilized in diagnostic and therapeutic applications. Herein, we report on the synthesis, structural characterization, solution speciation, and biological activity with mode of action studies of a new <i>fac</i>-tricarbonylrhenium-(I) complex with pyrithione ligand <i>fac</i>-[Re-(CO)₃(pyrithionato)-(benzonitrile)] (<b>4</b>). In an attempt to prepare a stable rhenium-(I) complex with a pyrithionato ligand, several synthesis procedures were investigated and various products were discovered. In solution, the monodentate benzonitrile ligand can be replaced by a coordinating solvent molecule; however, the carbonyl ligands and pyrithione remain bound to the rhenium center. Complex <b>4</b> exhibited strong cytotoxic and antibacterial activity and effectively inhibited the growth of the HSV-2 virus. Additionally, complex <b>4</b> was also able to inhibit the cathepsin B enzyme (both its endo- and exopeptidase activities). <i>In silico</i> experiments confirmed that complex <b>4</b> can interact with cathepsin B near its active site, which may contribute to reduced enzymatic activity.