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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 \( \left[ {{\text{Rh}}^{\text{III}}_{ 2} \left( {\text{HA}} \right)_{ 4} } \right]^{ 2- } \) 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 RhIII center, and the RhIII··RhIII 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 RhIII–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.

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Abbreviations

CPMAS:

Cross-polarization magic angle spinning

ESI-MS:

Electrospray ionization mass spectrometry

EXAFS:

X-ray absorption fine structure

XANES:

X-ray absorption near-edge structure

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Acknowledgements

We are grateful to Mr. Wade White at the instrumentation facility at the Department of Chemistry, University of Calgary, for his assistance in measuring the ESI-mass spectra. Special thanks to Dr. Glenn Facey for useful discussions and measuring the solid state 13C CPMAS NMR spectra at the NMR facility at the Department of Chemistry, University of Ottawa. A.E.G acknowledges University of Calgary Eyes High, and Faculty of Science Dean’s Open Competitions Doctoral Scholarships. This work was financially supported by the Natural Science and Engineering Research Council of Canada (NSERC), Canadian Foundation for Innovation (CFI), the Province of Alberta (Department of Innovation and Science) and the University of Calgary (URGC SEED Grant). X-ray absorption data collection was carried out at the Stanford Synchrotron Radiation Lightsource (SSRL; Proposal no. 3637). Use of the SSRL, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract no. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH.

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Correspondence to Farideh Jalilehvand.

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775_2017_1524_MOESM1_ESM.pdf

Supplementary material 1 (PDF 1897 kb) ESI-mass spectra of RhIII-GSH solid (2), and the Rh2(AcO)4–glutathione solution mixture at 0 and 80 V measured in (−) and (+) ion modes; separate contributions of different scattering paths in the EXAFS spectra of compound 2; S K-edge XANES spectrum of RhIII-GSH solid (2) and the Rh(III) N-acetylcysteine compound (3). For the Rh2(AcO)4–glutathione reaction at the pH of mixing (acidic) see Appendix 1, with UV–Vis and ESI-mass spectra for the Rh2(AcO)4-glutathione solution

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Enriquez Garcia, A., Jalilehvand, F. Aerobic reactions of antitumor active dirhodium(II) tetraacetate Rh2(CH3COO)4 with glutathione. J Biol Inorg Chem 23, 231–239 (2018). https://doi.org/10.1007/s00775-017-1524-6

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  • DOI: https://doi.org/10.1007/s00775-017-1524-6

Keywords

  • Glutathione
  • Dirhodium(II) tetraacetate
  • O2 reduction
  • Structure
  • Spectroscopy