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

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Wang, Fuyi, Weidt, Stefan, Xu, Jingjing, Mackay, C. Logan, Langridge-Smith, Pat R. R. and Sadler, P. J.. (2008) Identification of clusters from reactions of ruthenium arene anticancer complex with glutathione using nanoscale liquid chromatography fourier transform ion cyclotron mass spectrometry combined with 18O-labeling. Journal of The American Society for Mass Spectrometry, Vol.19 (No.4). pp. 544-549. ISSN 1044-0305

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Official URL: http://dx.doi.org/10.1016/j.jasms.2007.12.002

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-GIU-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-TCR 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 (OH2)-O-18 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.

Item Type: Journal Article
Subjects: Q Science > QC Physics
Q Science > QD Chemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Ruthenium compounds, Antineoplastic agents, Mass spectrometry, Fourier transform spectroscopy, Liquid chromatography, Nanochemistry, Glutathione
Journal or Publication Title: Journal of The American Society for Mass Spectrometry
Publisher: Springer New York LLC
ISSN: 1044-0305
Date: April 2008
Volume: Vol.19
Number: No.4
Number of Pages: 6
Page Range: pp. 544-549
Identification Number: 10.1016/j.jasms.2007.12.002
Status: Peer Reviewed
Publication Status: Published
Funder: Research Councils UK (RCUK), Zhongguo ke xue yuan [Chinese Academy of Sciences], Oncosense Ltd.
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URI: http://wrap.warwick.ac.uk/id/eprint/30205

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