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.
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.
Wang
Fuyi
F
School of Chemistry, University of Edinburgh, Edinburgh, UK.
Weidt
Stefan
S
Xu
Jingjing
J
Mackay
C Logan
CL
Langridge-Smith
Pat R R
PR
Sadler
Peter J
PJ
D000970:Antineoplastic Agents / Q000737:chemistry*; D017357:Cyclotrons; D005978:Glutathione; D007553:Isotope Labeling / Q000379:methods*; D036103:Nanotechnology / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry*; D010103:Oxygen Isotopes; D017975:Ruthenium Compounds / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010103:Oxygen Isotopes; D017975:Ruthenium Compounds; D005978:Glutathione