Disproportionation of a model chromium(V) complex causes extensive chromium(III)-DNA binding in vitro

Authors

Aviva Levina, University Of Sydney
Peter A. Lay, University Of Sydney
Nicholas E. Dixon, University of WollongongFollow

RIS ID

19874

Publication Details

Levina, A., Lay, P. A. & Dixon, N. E. (2001). Disproportionation of a model chromium(V) complex causes extensive chromium(III)-DNA binding in vitro. Chemical Research in Toxicology, 14 (8), 946-950.

Abstract

The first direct evidence for the role of Cr(V) complexes in the formation of potentially mutagenic Cr(III)-DNA adducts has been obtained. A model complex for the stabilized Cr(V) species formed in Cr(VI)-treated cells, [(CrO)-O-V(ehba)2](-) [ehba = 2-ethyl-2-hydroxybutanoato-(2-)], rapidly disproportionates in HEPES buffers at pH 7.4 [3 Cr(V) --> 2 Cr(VI) + Cr(III)], and the formed Cr(III) species undergo efficient ionic binding to DNA, followed by slower covalent binding. The extent of Cr(III)-DNA binding significantly exceeds that caused by [Cr-III(OH2)(6)](3+) or by the Cr(III) products of Cr(VI) reductions under similar conditions. The Cr(III)-DNA binding can be dramatically reduced by the ability of the reaction medium (e.g., phosphate buffer) to form complexes with Cr(III) during and after the disproportionation reaction. A mechanism of Cr(III)-DNA binding caused by Cr(V) disproportionation has been proposed on the basis of stoichiometric and kinetic studies.