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

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, [Cr(V)O(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)(OH(2))(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.