Aerobic reactions of antitumor active dirhodium(II) tetraacetate Rh2(CH3COO)4 with glutathione.

Abstract

The aerobic reaction between glutathione (H3A) and dirhodium(II) tetraacetate, Rh2(AcO)4 (AcO-=CH3COO-), in aqueous solution (pH 7.4) breaks up the direct RhII-RhII bond and its carboxylate framework, as evidenced by UV-Vis spectroscopy. After purifying the reaction product using size exclusion chromatography, electrospray ionization mass spectrometry (ESI-MS) of the solution showed binuclear [Formula: see text] and [Formula: see text] ions. Evaporation yielded a solid compound, [Formula: see text], for which Rh K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy revealed~2 Rh-O (2.08±0.02 Å) and~4 Rh-S (2.33±0.02 Å) bond distances around each RhIII center, and the RhIII··RhIII distance 3.11±0.02 Å, close to that in dirhodium(III) complexes with three bridging thiolates connecting [Formula: see text] units. The 13C CPMAS NMR spectrum of the RhIII-glutathione complex showed a change ∆δ C>6ppm in the chemical shift of the COO- signal, indicating some carboxylate coordination to the Rh(III) ions. This study shows that under aerobic conditions glutathione enables oxidation of Rh2(AcO)4 and thus reduces its antitumor efficiency. The reaction of Rh2(AcO)4 with glutathione was investigated by ESI-MS, UV-Vis, 13C NMR and X-ray absorption spectroscopy, revealing that glutathione breaks down the carboxylate framework enabling oxidization of the [Formula: see text] core to Rh(III) dimeric units, bridged by three thiolates.