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Alkylation introduces an alkyl group into a molecule. The new group may attach to carbon, nitrogen, oxygen, sulfur, or another suitable atom; the name alone does not specify the mechanism.

For example, an alkoxide can react with a suitable alkyl halide to form an ether by nucleophilic substitution, while Friedel-Crafts alkylation attaches an alkyl group to an aromatic ring through an electrophilic pathway. Competing elimination, multiple substitution, or rearrangement depends on the particular reacting partners.

Hiroko Koyama coauthored research on alkylation.^[ref]

Alkylation introduces an alkyl group into a molecule. The new group may attach to carbon, nitrogen, oxygen, sulfur, or another suitable atom; the name alone does not specify the mechanism.

Gerald M. Edelman reduced IgG disulfide bonds and used dissociating chemical solutions, including $6\mathrm{mol}{\mathrm{L}}^{-1}$ urea. Ultracentrifugal analysis showed a decrease in molar mass, supporting a multichain protein. In the comparison reproduced in his lecture, starch gel electrophoresis in urea separated serum IgG and a urinary protein from the same patient, alongside their reduced and alkylation-treated preparations. The untreated samples provided the treatment comparison; the urinary material provided a chain-identity comparison. The treated serum sample revealed heavy- and light-chain bands. Two-dimensional peptide mapping compared the urinary protein with the isolated immunoglobulin light chain. Together these readouts supported a shared chain identity.^[ref]

The controls address distinct alternatives. Treatment-dependent separation supports chains joined in the starting protein; a matching gel electrophoresis position alone would not uniquely identify a chain. Agreement of peptide mapping adds an independent chemical comparison. Neither readout gives atomic coordinates, and this patient's preparation does not establish a common protein primary structure for all antibodies.

Reduction targets protein disulfide bonds, while protein denaturation weakens the folded assembly. Neither operation is the proteolysis that cuts peptide bonds. This explains why chain separation and Papain digestion of IgG give different inventories: four intact chain backbones in the first case, three assembled fragments in the second.

Masaaki Suzuki coauthored research on alkylation.^[ref]

Alkylation introduces an alkyl group into a molecule. The new group may attach to carbon, nitrogen, oxygen, sulfur, or another suitable atom; the name alone does not specify the mechanism.

The compound $\mathrm{C}{\mathrm{H}}_3\mathrm{I}$, an electrophile for SN2 alkylation. The carbon is attacked as iodide leaves.

The first base equivalent removes O–H; the second removes the alpha C–H. The first equivalent of lithium diisopropylamide converts the carboxylic acid to its lithium carboxylate. A further equivalent removes the remaining hydrogen on the carbon between the two allyl groups, giving a carboxylic acid dianion:The second negative charge has enolate-like delocalization into the carboxyl group; lithium coordination and aggregation are not represented by this simple charge-bookkeeping structure. The carbon nucleophile attacks methyl iodide with C–I bond cleavage, forming the new C–Me bond. acid workup reprotonates the carboxylate, giving $F=\mathrm{H}{\mathrm{O}}_2\mathrm{C}-\mathrm{C}(\mathrm{Me})(\mathrm{L}{)}_2$. The two equivalents are therefore chemically necessary for the stated carbon alkylation rather than simply an arbitrary excess. A single equivalent is consumed predominantly by the much more acidic carboxylic proton. The product has formula ${\mathrm{C}}_9{\mathrm{H}}_{14}{\mathrm{O}}_2$ and still has two identical allyl groups, so this methylation does not create a stereocenter.

The malonate carbon receives two allyl groups. With $L=\mathrm{C}{\mathrm{H}}_2\mathrm{CH}=\mathrm{C}{\mathrm{H}}_2$, attached through its first carbon, the product issodium hydride removes a methylene proton from diethyl malonate; molecular hydrogen formation accompanies production of an enolate stabilized by resonance in chemistry. Its carbon attacks the bromomethylene carbon of allyl bromide in an SN2 reaction, expelling bromide. The monoalkylated malonate still has one hydrogen between the carbonyls. Excess base removes that hydrogen, and a second equivalent of allyl bromide produces a second carbon–carbon bond. The final malonate carbon has no remaining hydrogen and cannot undergo a third analogous deprotonation there.

The two alkenes are preserved because the substitution occurs at the primary carbon bearing bromine. Counting the introduced groups gives ${\mathrm{C}}_{13}{\mathrm{H}}_{20}{\mathrm{O}}_4$ for the diallylated diethyl ester. Its two identical allyl groups also mean that the central carbon is not a stereocenter. This stage is the alkylation portion of the malonic ester synthesis.

Researcher in RNA measurement. Herzog and collaborators developed thiol-linked alkylation for following RNA-expression dynamics, connecting a chemical labeling strategy with estimates of transcript production and persistence.^[ref]