Title

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

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.

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Link to publisher version (DOI)

http://dx.doi.org/10.1021/tx010077g