Mercury dealkylation

Photolysis of pentobarbitone (pentobarbital, 285) was achieved on a solution buffered to pH 11 with a low-pressure mercury lamp over 10 h. At this pH the mono anion was the main species present. The products identified were the dealkylated ethyl barbitone (286), the amide (294) and both diastereoisomers of the ureide (295). On more prolonged irradiation, there also appeared ethylhydroxybarbitone (287) and an unidentified dimeric compound. When ethylbarbitone (286) was photolysed in the same way, it gave (287) and 2-ethyl-2-hydroxymalonic acid. Finally, pentobarbitone was irradiated in molar sodium hydroxide solution, where the dianion would be the main form present, to give (295) with a small amount of (294) [175]. 

The above reactions in this section have been examples of addition alone or addition followed by elimination. Ligand reactions involving nucleophilic substitution are also known and these are of the dealkylation type. Lewis acids such as aluminum chloride or tin(IV) chloride have been used for many years in the selective demethylation of aromatic methyl ethers, where chelation is involved (Scheme 27). Similar cleavage of thioethers, specially using mercury(II) salts, is commonly used to remove thioacetal functions masking ketones (equation 27).104 In some cases, reactions of metal ions with thioether ligands result in isolation of complexes of the dealkylated organic moiety (equations 28 and 29).105-107... 

Thus, the toxicity of DMM is mediated by its dealkylation. Cleavage of the carbon-mercury bond generates MMM metabolites, which can form covalent bonds with cellular ligands with amphiphilic properties. The mercury center reacts with sulfur and sulfur-containing thiol groups of enzymes and thereby inhibits them. The metal center of DMM acts as a soft acid, and binds tightly to polarizable donor atoms in soft bases. Within cells, mercury may interact with a variety of proteins, particularly microsomal and mitochondrial enzymes. This can severely impair cell function. 

The autopsy of a man whose first symptoms of methylmercury poisoning occurred 26 years earlier revealed that the highest mercury levels (0.62-1.19 g Hg/g) were in the gyrus of the cerebral cortex, cerebellum, pallidum, and occipital pole of the brain (Takeuchi et al. 1989). Furthermore, total mercury levels (0.02-1.19 g/g) were much higher than methylmercury levels (approximately <0.01 g/g) in the brain. This finding supports the assumption by Suda et al. (1989) that ingested methylmercury is dealkylated to inorganic mercury in the brain. 

Studies of the mercury-photosensitised decomposition of 2-azetidinone and 4,4-dimethyl-2-azetidinone have been described the major products in the latter case were carbon monoxide, 2-methylpropene and 2,2-dimethylaziridine. Examples of photo-chemically induced N-dealkylation have again been reported. 

Microbial demethylations, or dealkylations, of organometallic forms are important reactions in detoxification mechanisms for some metals, such as mercury and tin. Bacterial detoxification of organomercurials is well established and involves the enzyme organomercurial lyase (OL)—a product of the merB gene—that enzymatically cleaves the Hg-C bond to form Hg, which is then reduced by the enzyme mercuric reductase (MR) to the less toxic Hg(0) (Equations (4) and (5)). The high volatility of Hg(0) results in it being rapidly removed to the atmosphere. 

Lack of isotopic exchange between organic and inorganic mercury derivatives in the Ottawa River sediments suggests that the changes in relative amounts arise from specific alkylation or dealkylation reactions. The methylation of lead ions in rivers by bacterial agency has been confirmed. ... 

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