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 Rh^II–Rh^II 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 Rh2IIIHA42- and Rh2IIIHA54- ions. Evaporation yielded a solid compound, Na2Rh2IIIHA4·7H2On, 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 Rh^III center, and the Rh^III··Rh^III distance 3.11 ± 0.02 Å, close to that in dirhodium(III) complexes with three bridging thiolates connecting Rh2III units. The ¹³C CPMAS NMR spectrum of the Rh^III–glutathione complex showed a change ∆δC > 6 ppm 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.Graphical Abstract: 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 Rh24+ core to Rh(III) dimeric units, bridged by three thiolates. [ABSTRACT FROM AUTHOR]

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