Ligand Exchange/Scrambling Study of Gold(I)-Phosphine Complexes in the Solid Phase by DESI-MS Analysis
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J. Am. Soc. Mass Spectrom. (2019) DOI: 10.1007/s13361-019-02319-y
RESEARCH ARTICLE
Ligand Exchange/Scrambling Study of Gold(I)-Phosphine Complexes in the Solid Phase by DESI-MS Analysis Syed G. T. Kazimi,1 Mohammad S. Iqbal,2 Christopher C. Mulligan,3 C. Frank Shaw III,3 Fozia Iram,4 Ashley R. Stelmack,3 Ian S. Campbell5 1
Department of Chemistry, University of Sargodha, Sargodha, 40100, Pakistan Department of Chemistry, Forman Christian College, Lahore, 54600, Pakistan 3 Department of Chemistry, Illinois State University, Normal, IL 61790-4160, USA 4 Department of Chemistry, LCW University, Lahore, 54600, Pakistan 5 Department of Chemistry and Physics, Florida Gulf Coast University, Fort Myers, FL 33965-6565, USA 2
Abstract. 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 MSbased 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-acetylβ-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. Keywords: Gold complexes, Auranofin, Ligand exchange, Ligand scrambling, DESI-MS, Ambient mass spectrometry Received: 10 April 2019/Revised: 4 July 2019/Accepted: 10 August 2019
Introduction
G
old complexes are known to exhibit medicinal properties, [1, 2] and their modern clinical use dates back to 1929. Various gold(I) thiolates including sodium aurothiomalate and auranofin, (2,3,4,6-tetra-O-acetyl-β-1-D-glucopyranosato-S)triethylphosphine gold(I), have been used to treat conditions Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s13361-019-02319-y) contains supplementary material, which is available to authorized users. Correspondence to: Mohammad Iqbal; e-mail: [email protected]
such as rheumatoid arthritis. Auranofin is now under clinical trials as an anti-cancer drug, and it has also shown great promise for treatment of parasitic diseases [3]. Numerous other gold(III) species exhibiting anti-tumor activity are also currently under investigation as therapeutics
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