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

The aerobic reaction between glutathione (H 3 A) and dirhodium(II) tetraacetate, Rh 2 (AcO) 4 (AcO − = CH 3 COO − ), 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 Rh 2 III HA 4 2 - and Rh 2 III HA 5 4 - ions. Evaporation yielded a solid compound, Na 2 Rh 2 III HA 4 · 7 H 2 O n , 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 Rh 2 III units. The 13 C CPMAS NMR spectrum of the Rh III –glutathione complex showed a change ∆ δ C > 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 Rh 2 (AcO) 4 and thus reduces its antitumor efficiency. Graphical Abstract The reaction of Rh 2 (AcO) 4 with glutathione was investigated by ESI-MS, UV–Vis, 13 C NMR and X-ray absorption spectroscopy, revealing that glutathione breaks down the carboxylate framework enabling oxidization of the Rh 2 4 + core to Rh(III) dimeric units, bridged by three thiolates.