Dirhodium(II) carboxylates, with formula Rh2(µ-RCOO)4, have shown remarkable anticancer properties, and are considered as potential chemotherapeutics. Their mechanism of action has not been fully explored, but a few mechanisms have been suggested, including the inhibition of DNA replication by direct DNA binding, and the inhibition of transcription due to redox reactions with thiol groups on T7-RNA polymerase. It is known that thiol-containing enzymes are irreversibly inhibited by dirhodium(II) carboxylates, leading to the breakdown of their paddlewheel structure. Recently, we investigated the reactions of Rh2(CH3COO)4 with glutathione, L-cysteine and its derivatives, and structurally characterized the products as multi-nuclear Rh(III) complexes with bridging thiolate groups. These findings motivated us to further study the interaction of Rh2(CH3COO)4 with the other S-containing amino acid, methionine (HMet). Earlier studies suggest that methionine can only coordinate to the axial positions of Rh2(CH3COO)4 via its thioether group. However, upon heating the reaction mixture close to body temperature, we found that a new stable half-paddlewheel complex, Rh2(CH3COO)2(Met)2, can be formed (see Figure). In this structure, two methionine ligands have displaced two of the acetate groups and coordinate in a tridentate manner. Cell viability studies, alongside X-ray fluorescence microscopy (XFM) studies, showed no toxicity and poor uptake of this complex, as compared with the parent compound, Rh2(CH3COO)4, probably due to its occupied axial positions. Colocalization with Zn and P in the elemental maps suggests that Rh2(CH3COO)4 mainly targets the nucleus of the cell. The information derived from this research presented at this conference, will shed some light into the metabolic fate of dirhodium(II) complexes in presence of thioether-containing biomolecules, and emphasize on the importance of available axial positions for their cytotoxic properties.

Disruption of the anticancer activity of dirhodium(II) tetraacetate by amino acid methionine

2019 Spring National Meeting

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