Thermodynamic Analysis of Arsenic Methylation

Abstract

The Challenger mechanism for the methylation of arsenic is a repeating sequence of a two-electron reduction of pentavalent arsenic As(V) species to trivalent arsenic As(III) species followed by a methylation-oxidation reaction forming the successive methyl As(V) species. This unusual oxidation-reduction sequence prompted an examination of the thermodynamics of these reactions. Quantum chemical methods are employed to estimate the thermodynamic parameters for the methyl arsenic species. The sequence is thermodynamically favored at neutral pH for redox potentials with pe < 0 and methyl cation activities pCH3+ < -3 to -7 depending on the precise situation analyzed. The observed distribution of methyl arsenic species in human urine, which is remarkably constant across many studied populations, can be reproduced using an equilibrium model if the formation of TMA species is prevented. The estimated thermodynamic parameters are sufficiently accurate to evaluate questions of thermodynamic plausibility but not the precise details of speciation.

Microbial responses to environmental arsenic

“…Yet, the methylation pathway(s) proposed for prokaryotes are the same as those described in the early studies (Challenger 1951) on the subject with the fungus Scopulariopsis brevicaulis. The general picture is that methylation pathway(s) involve a series of steps in which the reduction of the pentavalent form of As is followed by the oxidative addition of a methyl group (Dombrowski et al 2005) thereby generating a growingly methylated series of As chemical species: methyl arsenite (MMA), dimethyl arsenate (DMA-V), dimethyl arsenite (DMA-III) and trimethyl arsine oxide (TMAO). While glutathione and other thiol-containing compounds participate in the reduction steps, anaerobic bacteria may use methylcobalamin as the electron donor (Krautler 1990;Stupperich 1993).…”

Arsenic Chemistry

“…The methylation of arsenic by microorganisms may be described with the Challenger mechanism (Bentley and Chasteen, 2002), 254-255; (Dombrowski et al, 2005). The mechanism consists of a series of reduction and oxidative methylation reactions (2.11-2.21, below) that begin with the reduction of inorganic As(V) to inorganic As(III) and end with the formation of trimethylarsine (Figure 2.2).…”

Microbial transformation of arsenic species in municipal landfill leachate

“…Observing MMA III and DMA V in the MMA V -spiked MLL demonstrates bacteria in MLL are capable of reducing a fraction of MMA V to MMA III and methylating to DMA V , which is consistent with Challenger's biomethylation of MMA V [11,12]. Nevertheless, further methylation of DMA V to trimethylarsine oxide (TMAO) was not observed in the DMA V -spiked MLL [26], suggesting transformation of DMA V to thiol-organoarsenic species is preferred over TMAO formation in MLL.…”

“…The reduction of iAs V to iAs III and further methylation generally increase its mobility and consequently its availability within the environment [8][9][10]. Challenger postulated iAs V biomethylation involved a repeated sequence of pentavalent arsenic reduction to trivalent arsenic, followed by oxidative methylation to methyl arsenic species [11,12].…”