Nmethylation

N-methylation, or N-methylation, is the transfer of a methyl group to a nitrogen atom within a molecule. In chemistry, it commonly converts amines into higher N-substituted amines, ranging from secondary amines to quaternary ammonium salts, and can modify other nitrogen-containing groups. Typical methyl donors include methyl iodide, dimethyl sulfate, and methyl triflate; reactions often proceed by SN2 on a primary amine or by formation of a quaternary ammonium salt with excess reagent. Reductive or transfer methods, such as reductive methylation of aldehydes or the Eschweiler–Clarke methylation (formaldehyde and formic acid), are used to install one or more methyl groups while tuning basicity and reactivity.

In biology, N-methylation is catalyzed by methyltransferase enzymes that transfer a methyl group from S-adenosylmethionine to nitrogen atoms in substrates. Protein N-methylation commonly targets lysine and arginine residues, influencing protein interactions, signaling, and gene regulation. Histone methyltransferases modify chromatin states, while arginine methyltransferases generate mono- or dimethylarginine. In nucleic acids, N-methylations occur on bases (for example, N7-methylguanine in RNA caps and N1- or N6-methyladenosine), affecting stability, translation, splicing, and repair. These enzymatic methylations can be reversible, with specific demethylases or repair pathways modulating the modifications.

The effects of N-methylation depend on the site and extent, altering basicity, hydrogen bonding, polarity, and molecular recognition. Dysregulated methylation is linked to disease, but targeted methylation is central to drug design and epigenetic regulation. Safety considerations for chemical N-methylation include handling hazardous methylating agents and controlling over-methylation or unintended quaternization.