Methylate

Methylate refers to the process of adding a methyl group, CH3, to an organic substrate. The verb form to methylate is used to describe this modification. Methylation is a common transformation in chemistry and biology, used to alter reactivity, physicochemical properties, or biological activity.

In organic synthesis, methylation is achieved with methylating agents that transfer CH3+. Common agents include methyl iodide, dimethyl sulfate, and methyl triflate. Reactions proceed by electrophilic methylation of nucleophilic sites such as oxygen, nitrogen, or sulfur (O-, N-, S-methylation) or, less commonly, carbon centers under forcing conditions. Selectivity depends on nucleophilicity, sterics, and solvent; protecting-group strategies often rely on methylation to mask reactive sites.

Biological methylation: In biochemistry, methylation is carried out by methyltransferase enzymes using S-adenosyl-L-methionine (SAM) as the methyl donor. DNA methylation, typically at the 5-position of cytosine in CpG dinucleotides, is a key epigenetic modification affecting gene expression, development, and genome stability. RNA, proteins, and small molecules can also be methylated, influencing function and interactions. Methylation states are often dynamic and can be reversed by demethylases and related repair pathways.

Applications and significance: Methylation plays a crucial role in drug design, biosynthesis, and epigenetic research. It influences metabolism and pharmacokinetics through methylated metabolites and, in living systems, methylation patterns can change during development and disease.