Synthesis of Cr(IV)-GSH, its identification and its free hydroxyl radical generation: A model compound for Cr(VI) carcinogenicity

Ke Jian Liu, Xianglin Shi, Nar S. Dalal

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65 Scopus citations


Current models of Cr(VI) carcinogenesis suggest an important role for Cr(IV) as an intermediate, toxic, carcinogenic species, but direct chemical evidence has been lacking. This is because Cr(IV) is a highly reactive oxidation state of Cr and few Cr(IV)-based compounds are known that can be used as a model compound containing a biological ligand. This study reports the isolation of such a stable Cr(IV) complex. The Cr(IV)-GSH complex has been synthesized through the reaction of Cr(VI) with GSH. Its electron paramagnetic resonance (EPR) spectrum exhibits g = 1.9629 and a peak-to-peak line width of 480 G in aqueous medium as well as in the powder form. Magnetic susceptibility measurements showed that the compound has a magnetic moment of 2.53 Bohr magneton per Cr, establishing that the Cr ion has two unpaired electrons, hence its identity as Cr(IV). The Cr(IV)-GSH complex is able to generate hydroxyl (.OH) radical in the presence of molecular oxygen in aqueous medium. Catalase inhibited the .OH radical generation while H2O2 enhanced it, indicating that the .OH radical was generated via a Fenton-like reaction, H2O2 being generated as an intermediate in the reduction of molecular oxygen. Metal ion chelators, deferoxamine and 1,10-phenanthroline, attenuated the generation of Cr(IV)-mediated .OH radical. In the case of deferoxamine, a deferoxamine-derived free radical was generated as shown by EPR measurements. The results imply that Cr(IV) may play an important role in the mechanism of Cr(VI)induced carcinogenesis and Cr(IV)-GSH can be used as a model compound to study the role of Cr(IV) in this mechanism.

Original languageEnglish
Pages (from-to)54-58
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Jun 9 1997

Bibliographical note

Funding Information:
We wish to thank Dr. Alex Smirnov, University of Illinois, for performing the magnetic susceptibility measurements. NSD thanks Florida State University for a partial support of this work. This research used the facilities of the EPR Center for the Study of Viable Systems at Dartmouth supported by the National Institute of Health Grant P41 RR11602-01A1.

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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