Structure and Reactivity of a Chromium(V) Glutathione Complex¹

Abstract

Chromium(V) glutathione complexes are among the likely reactive intermediates in Cr(VI)-induced genotoxicity and carcinogenicity. The first definitive structure of one such complex, [Cr(V)O(LH(2))(2)](3)(-) (I; LH(5) = glutathione = GSH), isolated from the reaction of Cr(VI) with excess GSH at pH 7.0 (O'Brien, P.; Pratt, J.; Swanson, F. J.; Thornton, P.; Wang, G. Inorg. Chim. Acta 1990, 169, 265-269), has been determined by a combination of electrospray mass spectrometry (ESMS), X-ray absorption spectroscopy (XAS), EPR spectroscopy, and analytical techniques. In addition, Cr(V) complexes of GSH ethyl ester (gamma-Glu-Cys-GlyOEt) have been isolated and characterized by ESMS, and Cr(III) products of the Cr(VI) + GSH reaction have been isolated and characterized by ESMS and XAS. The thiolato and amido groups of the Cys residue in GSH are responsible for the Cr(V) binding in I. The Cr-ligand bond lengths, determined from multiple-scattering XAFS analysis, are as follows: 1.61 A for the oxo donor; 1.99 A for the amido donors; and 2.31 A for the thiolato donors. A significant electron withdrawal from the thiolato groups to Cr(V) in I was evident from the XANES spectra. Rapid decomposition of I in aqueous solutions (pH = 1-13) occurs predominantly by ligand oxidation with the formation of Cr(III) complexes of GSH and GSSG. Maximal half-lives of the Cr(V) species (40-50 s at [Cr] = 1.0 mM and 25 degrees C) are observed at pH 7.5-8.0. The experimental data are in conflict with a recent communication (Gaggelli, E.; Berti, F.; Gaggelli, N.; Maccotta, A.; Valensin, G. J. Am. Chem. Soc. 2001, 123, 8858-8859) on the formation of a Cr(V) dimer as a major product of the Cr(VI) + GSH reaction, which may have resulted from misinterpretation of the ESMS and NMR spectroscopic data.

Reductive activation of hexavalent chromium by human lung epithelial cells: Generation of Cr(V) and Cr(V)-thiol species

“…Similar lines in the g = 5 region have been reported following the reduction of Cr(VI) by GSH [53]. We observed broader lines in this region following extended incubation of Cr(III) with GSH ( Fig.…”

“…Levina et al [53] reported a similar spectrum for GSH plus Cr(VI) at pH 7.0, and for a Cr(V)-GSH complex dissolved in water for two min. Their signal for the Cr(V)-GSH complex (g = 1.996) diminished by 7 min as the GSH-Cr(V) complex decomposed, whereas the intensity of the g = 1.986 signal increased [53]. They reported that all ESR signals from this Cr(V)-GSH complex disappeared after 10 min, indicating instability in aqueous solution.…”

“…2 are due to Cr(V), analogous studies were conducted with isotopically pure 53 Cr (stable isotope) as Na 2 53 CrO 4 . Because 53 Cr has a nuclear spin of I = 3/2, Cr(V) signals will be split into four lines (separation of 17.4 G), typical for the hyperfine coupling for 53 Cr(V) [44].…”

“…Because 53 Cr has a nuclear spin of I = 3/2, Cr(V) signals will be split into four lines (separation of 17.4 G), typical for the hyperfine coupling for 53 Cr(V) [44]. With 53 Cr, both the g = 1.979 and g = 1.985 components of the Cr(V) signal ( …”

“…The Cr(III)-histidine complex may be similar in structure to the Cr(III)-GSH in which non-thiol residues (e.g. γ-Glu of GSH or GSSG) provide the ligands for Cr(III) [53]. The cellular signal at g = 1.94 is likely due to iron-sulfur complexes (usually oxidized) and can be seen in cells and tissues incubated without Cr(VI) [54].…”