Ligand Exchange/Scrambling Study of Gold(I)-Phosphine Complexes in the Solid Phase by DESI-MS Analysis
Only a few analytical techniques are available for the characterization of mechanochemical synthetic reaction products. We demonstrate here that DESI-MS is a powerful technique for this purpose, combining the selectivity of MS-based assays with the simplicity and in situ analysis capability of ambient ionization methods. In this work, we report that auranofin, a gold-based drug, and its precursor triethylphosphine gold(I) chloride undergo a complex array of ligand exchange/scrambling reactions with thiol-containing amino acids in the solid state. The products were readily characterized by DESI-MS analysis from the solid-phase reaction, clearly exhibiting ligand exchange and scrambling, with independent confirmation by solid state 13C-NMR. The thioglucose and triethylphosphine moieties exchanged with cysteine and its derivatives, whereas the glutathione replaced 2,3,4,6-tetra-o-acetyl-β-1-d-glucopyranose only. It was concluded that ligand exchange and scrambling reactions can be carried out in the solid state, and some of the unique products reported in this study can be conveniently prepared through mechanochemical synthesis in good yields (> 98%), as demonstrated by synthesis of (l-cysteinato-S)-triethylphosphine gold(I) from triethylphosphine gold(I) chloride and l-cysteine.
KeywordsGold complexes Auranofin Ligand exchange Ligand scrambling DESI-MS Ambient mass spectrometry
The authors would like to dedicate this work to the late C. Frank Shaw III and his research in metal-based therapeutics. SGTK acknowledges HEC Pakistan for a PhD scholarship award.
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