Mechanism of multi‐metal(loid) methylation and hydride generation by methylcobalamin and cob(I)alamin: a side reaction of methanogenesis

Abstract

a Metal(loid)s are subject to many transformation processes in the environment, such as oxidation, reduction, methylation and hydride generation, predominantly accomplished by prokaryotes. Since these widespread processes affect the bioavailability and toxicity of metal(loid)s to a large extent, the investigation of their formation is of high relevance. Methanogenic Archaea are capable of methylating and hydrogenating Group 15 and 16 metal(loid)s arsenic, selenium, antimony, tellurium, and bismuth due to side reactions between central methanogenic cofactors, methylcobalamin (CH 3 Cob(III)) and cob(I)alamin (Cob(I)). Here, we present systematic mechanistic studies on methylation and hydride generation of Group 15 and 16 metal(loid)s by CH 3 Cob(III) and Cob(I). Pentavalent arsenical species showed neither methylation nor reduction as determined by using a newly developed oxidation state specific hydride generation technique, which allows direct determination of tri-and pentavalent arsenic species in a single batch. In contrast, efficient methylation of trivalent species without a change in oxidation state indicated that the methyl transfer does not proceed via a Challenger-like oxidative methylation, but via a non-oxidative methylation. Our findings also point towards a similar mechanism for antimony, bismuth, selenium, and tellurium. Overall, we suggest that the transfer of a methyl group does not involve a free reactive species, such as a radical, but instead is transferred either in a concerted nucleophilic substitution or in a caged radical mechanism. For hydride generation, we propose the intermediate formation of hydridocobalamin, transferring a hydride ion to the metal(loid)s.

Impact of Microorganisms on Arsenic Biogeochemistry: A Review

“…This suggests that either microorganisms have the ability to reduce As(III) or use other methylation pathways for methylation directly using As(V). Although several methylation pathways have been proposed (Mestrot et al 2013;Wu 2005;Wuerfel et al 2012), the current state of knowledge is still not able to explain the occurrence of methyl As of different chemical forms in nature and their linkage to the different enzymatic systems involved in microbial methylation; e.g. As(V) reductase, monomethylarsonic acid reductase, As(III) methyltransferase and monomethylarsonous acid methyltransferase (Wu 2005).…”

Selective hydride generation-cryotrapping-ICP-MS for arsenic speciation analysis at picogram levels: analysis of river and sea water reference materials and human bladder epithelial cells

“…Reports of HG-CT applications in connection with ICP-MS detection are surprisingly scarce. [11][12][13][14][15][16] The principal drawback of the HG-based approach is its limited selectivity, as the CT step can only distinguish four volatile As species, arsine and mono-, di-and trimethylarsine. Therefore, the selectivity of the analysis is aided by the HG step because some As species do not form hydrides under certain conditions.…”

The Methylation of Metals and Metalloids in Aquatic Systems

“…Additionally, it was demonstrated that methylation of As(V) did not occur and that methylation of As(III) did not involve oxidation, and was therefore similar in process to the methylation of Hg whereby the methyl group is added as a carbanion rather than a carbocation. While Weufel et al [10] were able to demonstrate the formation of higher methylated compounds, another study [11] suggested that the reaction pathway produces only monomethylated forms, which contrasts the environment where higher methylated forms are often more abundant. In addition to methylation of As, cobalamin has also been shown to methylate Sb [11].…”

“…In this case, it has been suggested that methylation may involve cobalamin and therefore involve a different mechanism whereby a carbanion or a radical from methylcobalamin is added to As III in the presence of mediating enzymes [4,7]. Methanogenic Achaea, for example, were shown to methylate a variety of metalloids of Groups 15 and 16 (As, Se, Sb, Te, and Bi) [10]. The mechanism was attributed to side reactions with methylcobalamin.…”

“…Therefore, the various pathways of methylation are entirely distinct and which pathway dominates is a function of the differences in the speciation and oxidation state of the metal and metalloid in aquatic systems. For example, there is some evidence for the methylation of As and other metalloids in anoxic sediments via the cobalamin pathway [5,10,11]. In contrast to metal cations, the metalloids are present in environmental solutions mostly as an oxyanion of a weak acid, and therefore their form depends on pH.…”