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 $\left[ {{\text{Rh}}^{\text{III}}_{ 2} \left( {\text{HA}} \right)_{ 4} } \right]^{ 2- }$ and $\left[ {{\text{Rh}}^{\text{III}}_{ 2} \left( {\text{HA}} \right)_{ 5} } \right]^{ 4- }$ ions. Evaporation yielded a solid compound, $\left\{ {{\text{Na}}_{ 2} \left[ {{\text{Rh}}^{\text{III}}_{ 2} \left( {\text{HA}} \right)_{ 4} } \right] \cdot 7 {\text{H}}_{ 2} {\text{O}}} \right\}_{n}$, 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 ${\text{Rh}}_{2}^{\text{III}}$ units. The ¹³C 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 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 ${\text{Rh}}_{ 2}^{ 4+ }$ core to Rh(III) dimeric units, bridged by three thiolates.