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

doi:10.1006/bbrc.1997.6277

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

Toxicology and Cancer Biology

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

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 language	English
Pages (from-to)	54-58
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	235
Issue number	1
DOIs	https://doi.org/10.1006/bbrc.1997.6277
State	Published - 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.

Funding

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.

Funders	Funder number
National Institutes of Health (NIH)	P41 RR11602-01A1
National Center for Research Resources	P41RR011602
Florida State University

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1006/bbrc.1997.6277

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

abstract = "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.",

author = "Liu, {Ke Jian} and Xianglin Shi and Dalal, {Nar S.}",

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.",

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AU - Liu, Ke Jian

AU - Shi, Xianglin

AU - Dalal, Nar S.

N1 - 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.

PY - 1997/6/9

Y1 - 1997/6/9

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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