The reactions of Cr(VI/V/IV) with a model thiolato complex [Zn(SR)2] (RSH = O-ethyl-l-cysteine), resembling a tetrahedral (2S,2N) Zn(II) binding site in zinc-finger proteins, have been studied in comparison with those of the free ligand. The stability of [Zn(SR)2] in aqueous solutions with pH 6−11 (25 °C, Ar-saturated) has been established by CD spectroscopy. Stoichiometries and products of the reactions of [Zn(SR)2] or RSH with [CrVIO4]2- or [CrVO(ehba)2]- (ehba = 2-ethyl-2-hydroxybutanoato(2−)) at pH 6.5−8.5 (25 °C, Ar) were studied by UV−vis and CD spectroscopies and by electrospray mass spectrometry. Disulfide (RSSR) is the only detectable oxidation product of both [Zn(SR)2] and RSH. In the case of RSH, relatively stable Cr(III) complexes, [CrIII(SR)3]0 and [CrIII(SR)2]+, are also formed and subsequently hydrolyzed to [CrIII(Cys)2]-. This is the first observation of a Cr(III)-facilitated hydrolysis of a cysteine ester. Ascorbate promotes the oxidation of [Zn(SR)2] by [CrVIO4]2-; this reaction leads to formation of RSSR and of the Cr(III)−thiolato complexes. Kinetics of the reactions of [Zn(SR)2] or RSH with [CrVIO4]2-, [CrVO(ehba)2]-, or [CrIVO(qa)(qaH)]- (qa = quinato(2−) = (1R,3R,4R,5R)-1,3,4,5-tetrahydroxycyclohexanecarboxylato(2−)) at pH 7.40 (25 °C, Ar) were studied by conventional and stopped-flow UV−vis spectrophotometry and by global kinetic analysis. Complexes of Cr(V) and Cr(IV) rapidly react with both the reductants, and reactions of Cr(V) pass through the Cr(IV) intermediates. By contrast with the reaction with RSH, the reaction of [CrVO(ehba)2]- with [Zn(SR)2] is not accompanied by a significant O2 consumption (measured by an oxygen electrode), suggesting the ability of [Zn(SR)2] to inhibit free radical reactions, similar to that of zinc metallothioneins. The mechanism of [Zn(SR)2] oxidation by Cr(VI/V/IV), including intramolecular formation of a disulfide bond, has been proposed. Implications of the results to the Cr(VI)-induced carcinogenesis and to the biological activity of Cr(III) are discussed.