| Abstract
| - Kinetics of disproportionation of 1 (reaction 1) and of plasmid DNA cleavage induced by 1 (reaction 2) have been studied in aqueous buffer solutions at pH 6.0−8.0, [NaClO4] = 1.0 M, and 37 °C. The first detailed mechanism of the reaction 1 has been proposed on the basis of a kinetic model. Reaction 2 is likely to be promoted by complexation of 1 with the phosphate backbone of DNA. Chromium(IV) intermediates are formed in reaction 1; however, they do not play an important role in reaction 2.
- Complex 1, [CrVO(ehba)2]- (ehba = 2-ethyl-2-hydroxybutanoate(2−)) is the most studied model compound ofrelevance to the biological activity of Cr(V) with regard to Cr-induced cancers. The first detailed kinetic study ofdisproportionation of 1 under neutral pH conditions (pH 6.0−8.0, [NaClO4] = 1.0 M, 37 °C) is reported. Kineticdata were collected by stopped-flow and conventional UV−vis spectroscopies and processed by the global analysismethod. The disproportionation, which follows the stoichiometry 3Cr(V) → 2Cr(VI) + Cr(III) (1), leads to releaseof 5 mol of H+/3 mol of Cr(V). Reaction 1 is accelerated by phosphate, but is not affected by acetate, HEPES,or Tris buffers. Initial rates of Cr(V) decay are directly proportional to [Cr(V)]0 (0.020−1.0 mM); they increasewith an increase in the pH values and decrease in the presence of a large excess of ehba ligand. The first directevidence for the formation of Cr(IV) intermediates in reaction 1 has been obtained; however, their UV−vis spectralproperties were different from those of the well-characterized Cr(IV)−ehba complexes. The Cr(III) products ofreaction 1 in phosphate buffers differ from those in the other buffers. A mechanism is proposed for reaction 1 onthe basis of kinetic modeling. Influences of the reaction time and conditions on the extent of plasmid DNAcleavage induced by 1 have been studied under conditions corresponding to those of the kinetic studies. Acomparison of the kinetic and DNA cleavage results has shown that direct interaction of 1 with the phosphatebackbone of DNA is the most likely first step in the mechanism of DNA cleavage in neutral media. Small additionsof Mn(II) ((0.01−0.1)[Cr(V)]0) did not affect the rate and stoichiometry of reaction 1, but suppressed the formationof Cr(IV) intermediates (presumably due to the catalysis of Cr(IV) disproportionation). However, much higherconcentrations of Mn(II) ((0.1−1.0)[Cr(V)]0) were required to inhibit DNA cleavage induced by 1. Thus, contraryto previous reports (Sugden, K. D.; Wetterhahn, K. E. J. Am. Chem. Soc. 1996, 118, 10811−10818), inhibitionby Mn(II) does not indicate a key role of Cr(IV) in Cr(V)-induced DNA cleavage.
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