Portal de Periódicos da CAPES

Solution Structures of Chromium(VI) Complexes with Glutathione and Model Thiols

2003; American Chemical Society; Volume: 43; Issue: 1 Linguagem: Inglês

10.1021/ic034901v

1520-510X

Aviva Levina, Peter A. Lay,

Radioactive element chemistry and processing

Chromium(VI) complexes of the most abundant biological reductant, glutathione (γ-Glu-Cys-Gly, I), are among the likely initial reactive intermediates formed during the cellular metabolism of carcinogenic and genotoxic Cr(VI). Detailed structural characterization of such complexes in solutions has been performed by a combination of X-ray absorption fine structure (XAFS) and X-ray absorption near-edge structure (XANES) spectroscopies, electrospray mass spectrometry (ESMS), UV−vis spectroscopy, and kinetic studies. The Cr(VI) complexes of two model thiols, N-acetyl-2-mercaptoethylamine (II) and 4-bromobenzenethiol (III), were used for comparison. The Cr(VI)−thiolato complexes were generated quantitatively in weakly acidic aqueous solutions (for I and II) or in DMF solutions (for II) or isolated as a pure solid (for III). Contrary to some claims in the literature, no evidence was found for the formation of relatively stable Cr(IV) intermediates during the reactions of Cr(VI) with I in acidic aqueous solutions. The Cr(VI) complexes of I−III exist as tetrahedral [CrO3(SR)]- (IVa) species in the solid state, in solutions of aprotic solvents such as DMF, or in the gas phase (under ESMS conditions). In aqueous or alcohol solutions, reversible addition of a solvent molecule occurs, with the formation of five-coordinate species, [CrO3(SR)L]- (IVb, probably of a trigonal bipyramidal structure, L = H2O or MeOH), with a Cr−L bond length of 1.97(1) Å (determined by XAFS data modeling). Complex IVb (L = H2O) is also formed (in an equilibrium mixture with [CrO4]2-) at the first stage of reduction of Cr(VI) by I in neutral aqueous solutions (as shown by global kinetic analysis of time-dependent UV−vis spectra). This is the first observation of a reversible ligand addition reaction in Cr(VI) complexes. The formation of IVb (rather than IVa, as thought before) during the reactions of Cr(VI) with I in aqueous solutions is likely to be important for the reactivity of Cr(VI) in cellular media, including DNA and protein damage and inhibition of protein tyrosine phosphatases.