Potentially Deadly Carcinogenic Chromium Redox Cycle Involving Peroxochromium(IV) and Glutathione

Abstract

Peroxochromium(IV) complexes are putative DNA-damaging and mutagenic agents in chromium(VI)-mediated carcinogenesis. The reaction between aquaethylenediaminebis(peroxo)chromium(IV) and glutathione at neutral pH exhibits a cyclic redox process displaying a persistent recycling of Cr(IV) and Cr(VI) with the intervention of chromium(V) intermediates. The coordination by a glutathione molecule triggers an autooxidation of the Cr(IV)-peroxo complex to Cr(VI) via an internal electron-transfer process followed by reduction to Cr(IV) via metastable chromium(V) intermediates. The cycle is repeated by the second peroxo species. The Cr(V) and -(IV) intermediates have been characterized as mono- and bisglutathionato complexes with or without a coordinated peroxo moiety. These intermediates are capable of damaging DNA, as evidenced by single strand breaks and DNA oxidation. The implication here is that the potential for a persistent, if not perpetual, deadly chromium carcinogenic cycle exists in the cellular milieu through the assistance of molecular oxygen and glutathione.

Magnetic Characterization of Hypervalent Chromium Intermediates in the Reduction of Chromium(VI) by Glutathione in Acidic Solutions

“…Therefore, we hypothesize that Cr(IV) intermediates accumulate and react with DNA and proteins forming adducts in which the metal is further reduced. Consistent with this framework, recently we reported the detection of a wide (peak-to-peak separation = 260 G) EPR signal at g 1.975 16 . This species was detected during the reaction of the complex aquaethylenediaminebis(peroxo)chromium(IV) hydrate (I) with GSH at neutral pH.…”

“…Moreover, the UV spectroscopy technique is not specific enough, especially when it is noted that these reactions produce more than one intermediate. In fact, in our 27 ESI-MS, cyclic voltammetry, EPR and HPLC studies of the reaction between aquaethylenediaminebis(peroxo)chromium(IV) hydrate (I) with GSH at neutral pH, we detected multiple intermediates of Cr(IV) and Cr(V) (mono and multi-ligated Cr-GSH species). Few workers, Bose 9 , Marin 27 , Liu 28 and Ramsey…”

Magnetic Characterization of Chromium Intermediates in the Reduction of Chromium (VI) by Glutathione in Acidic Solutions

“…Therefore, we hypothesize that Cr(IV) intermediates accumulate and react with DNA and proteins forming adducts in which the metal is further reduced. Consistent with this framework, we recently reported on the detection of a wide (peak-to-peak separation = 260 G) EPR signal with a g value of 1.975 [16]. This species was detected during the reaction of the complex aquaethylenediaminebis(peroxo)chromium(IV) hydrate (I) (Figure 1) with GSH at neutral pH.…”

“…Moreover, the UV spectroscopy technique is not specific enough, especially when it is noted that these reactions produce more than one intermediate. In fact, in our [16] ESI-MS, cyclic voltammetry, EPR, and HPLC studies of the reaction between aquaethylenediaminebis(peroxo)chromium(IV) hydrate (I) with GSH at neutral pH, we detected multiple intermediates of Cr(IV) and Cr(V) (mono and multi-ligated Cr-GSH species). Some researchers, including Bose et al [9], Marin et al [16], Liu et al [27], and Ramsey and Dalal [28], have paid attention to the potentially essential role of Cr(IV) in chromium carcinogenesis.…”

Organocatalytic conversion of cellulose into a platform chemical

“…The inefficiency of solid acid catalysts and the toxicity of heavy metals could diminish their impact. 9 Considering the ever-growing need for green chemistry, we sought a conversion process that uses benign and recyclable reagents, catalysts, and solvents, as well as mild reaction conditions. Here, we report on our discovery of such a process.…”