Identification of clusters from reactions of ruthenium arene anticancer complex with glutathione using nanoscale liquid chromatography Fourier transform ion cyclotron mass spectrometry combined with (18)O-labeling

Fuyi Wang, Stefan Weidt, Jingjing Xu, C Logan Mackay, Pat R R Langridge-Smith, Peter J Sadler

Research output: Contribution to journalArticlepeer-review

Abstract

Reactions of the anticancer complex [(eta(6)-bip)Ru(en)Cl](+) (where bip is biphenyl and en is ethylenediamine) with the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly; GSH), the abundant intracellular thiol, in aqueous solution give rise to two ruthenium cluster complexes, which could not be identified by electrospray mass spectrometry (ESI-MS) using a quadrupole mass analyzer. Here we use Fourier transform ion cyclotron mass spectrometry (nanoLC-FT-ICR MS) to identify the clusters separated by nanoscale liquid chromatography as the tetranuclear complex [{(eta(6)-bip)Ru(GSO(2))}(4)](2-) (2) and dinuclear complex [{(eta(6)-bip)Ru(GSO(2))(2)}(2)](8-) (3) containing glutathione sulfinate (GSO(2)) ligands. Use of (18)OH(2) showed that oxygen from water can readily be incorporated into the oxidized glutathione ligands. These data illustrate the power of high-resolution MS for identifying highly charged multinuclear complexes and elucidating novel reaction pathways for metallodrugs, including ligand-based redox reactions.
Original languageEnglish
Pages (from-to)544-549
Number of pages6
JournalJournal of the American Society for Mass Spectrometry
Volume19
Issue number4
DOIs
Publication statusPublished - 2008

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