Nmethylations

Nmethylations refers to the introduction of a methyl group onto a nitrogen atom in an organic molecule. It encompasses N-methylation of amines and related nitrogen-containing substrates. In chemistry and biochemistry, N-methylation can modify basicity, steric profile, and biological activity.

In synthetic chemistry, common routes include alkylation with methylating agents such as methyl iodide or dimethyl sulfate, which can yield mono-, di-, or trimethylated amines and, in excess, quaternary ammonium salts. Reductive methylation, using formaldehyde and a reducing agent (e.g., sodium cyanoborohydride), enables selective installation of one or two methyl groups. The Eschweiler–Clarke methylation (formaldehyde and formic acid) is another widely used method that introduces methyl groups on nitrogen.

Biology employs Nmethylation through methyltransferase enzymes that transfer a methyl group from S-adenosyl-L-methionine to nitrogen atoms. Examples include N-methylation of protein side chains such as lysine or arginine and RNA base methylation such as N6-methyladenosine. These modifications regulate gene expression, protein function, RNA processing, and chromatin dynamics. Some Nmethylations are reversible, and dysregulation is linked to disease.

Applications and considerations: N-methylation is a common strategy to modulate drug properties and binding characteristics. Regioselectivity, chemoselectivity, and avoidance of over-methylation are key concerns in synthesis, while in biology the specificity and scope of methyltransferases determine sites and extent of modification.