Methylation

METHYLATION, the introduction of the methyl radical (CH₃) into chemical compounds. Powerful methylating agents include: 1) diazomethane CH₂N₂ for phenols and bases; C₆H₅OH + CH₂N₂ = C₆H₅OCH₃ + N₂; 2) methyl iodide CH₃I, which attaches to amines with particular ease: R-NH₂ + CH₃I = R-NH-HI; 3) dimethyl sulfate SO₂(OCH₃)₂; 4) p-toluenesulfonic acid methyl ester C₆H₄(CH₃)-SO₂OCH₃. Methylation is of great importance in preparative organic chemistry, both in the laboratory and in industrial manufacturing, for example, in the technology of aniline dyes and medicinal substances. Methylation is also highly significant for elucidating the structure of certain classes of organic substances, such as carbohydrates. In the organism, methylation processes have long been known in warm-blooded animals: the formation of methyl telluride from tellurous acid (Hofmeister); the presence of methylated aminobutyric acid (formed from glutamic acid) in the urine of dogs poisoned by phosphorus; the methylation of nitrogenous substances introduced into the organism, such as pyridine and nicotinic acid; the formation of sarcosine NH(CH₃)-CH₂-COOH from glycocoll NH₂-CH₂-COOH; and the increased excretion of creatine and creatinine when feeding guanidinoacetic acid: HN=C(NH₂)-NH-CH₂-COOH (guanidinoacetic acid) → HN=C(NH₂)-N(CH₃)-CH₂-COOH (methylguanidinoacetic acid) = creatine. Evidence that methylation processes occur in the animal organism is also provided by the constant presence of methylated nitrogenous compounds such as creatine, methyl- and dimethylguanidine, adrenaline, trimethylamine, choline, betaine, carnitine, methylated purines, etc. According to Stuber, Russman, and Takahashi, methylation processes in animals are influenced by thyroid iodine: animals deprived of the thyroid gland lose the ability to methylate guanidinoacetic acid but regain this property upon the administration of thyroid preparations or iodine. Friedmann found that the substitution of hydrogen in the NH₂ group of fatty acid amino acids with methyl hinders their oxidation in the organism and makes them more resistant to putrefaction. Conversely, the methylation of aromatic compounds promotes their combustion in the organism (Fromherz and Hermanns, Ellinger and Matsuoka). Methylation processes are more vigorous in cold-blooded animals and plants than in warm-blooded ones (Ackermann). In plants, the methylation of amino acids occurs particularly frequently, leading to the formation of various betaines and alkaloids. Alongside methylation processes, the cleavage of methyl groups is also observed in the organism, for example, from methylpurines and choline.