Open AccessIdentification 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
Author(s) -
Fuyi Wang,
Stefan Weidt,
Jingjing Xu,
C. Logan Mackay,
Patrick R. R. LangridgeSmith,
Peter J. Sadler
Publication year - 2008
Publication title -
journal of the american society for mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.961
H-Index - 127
eISSN - 1879-1123
pISSN - 1044-0305
DOI - 10.1016/j.jasms.2007.12.002
Subject(s) - chemistry , mass spectrometry , fourier transform ion cyclotron resonance , ruthenium , glutathione , tripeptide , electrospray , ligand (biochemistry) , electrospray ionization , chromatography , organic chemistry , peptide , biochemistry , receptor , enzyme , catalysis
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.