DMTMM chloride | CAS 3945-69-5 | ≥95% (contains 15% H2O)

DMTMM (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; DMT-MM; the Kunishima reagent) is a triazine-based condensing agent for amide and ester bond formation, prepared from 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM). It is a pre-formed active reagent: a carboxylic acid forms a 2-acyloxy-4,6-dimethoxytriazine active ester, which then acylates an amine or alcohol to give the amide or ester, with water-soluble triazine and morpholinium by-products. Its defining feature is that it operates in protic and aqueous media — water, methanol and other lower alcohols — without solvent drying and without a separate carbodiimide, making it attractive where carbodiimide/NHS preactivation or dry organic solvent conditions are inconvenient. DMTMM chloride is supplied as a crystalline hydrate, soluble in water and lower alcohols; store cold and dry.

Amide and ester formation in protic and aqueous media

• Condenses carboxylic acids with amines to amides and with alcohols to esters, and converts carboxylic acids to Weinreb amides, under mild conditions.
• Reactions proceed in water, methanol and other lower alcohols, and in hydrous organic solvents without drying — the key practical distinction from many peptide-coupling reagents.
• No separate carbodiimide or NHS-type additive is required; the water-soluble triazine and morpholinium by-products are removed by aqueous extraction, washing or dialysis.

Peptide synthesis

• Activates carboxylic acids for solution-phase and solid-phase peptide coupling, including reported use in sterically hindered peptidomimetic synthesis.
• Its water and alcohol compatibility allows peptide and amino-acid couplings to be run in protic media where carbodiimide/NHS chemistry or dry organic conditions are less convenient.

Bioconjugation and biomacromolecule modification

• Activates carboxyl groups on proteins, polysaccharides and synthetic polymers for amide coupling in water, supporting chemical modification and conjugation of biomacromolecules.
• Couples carboxyl-bearing polysaccharides to amine partners, including carrier proteins and microsphere supports for immunoassay and glycoconjugate research.
• It has been used for polymer-analogous conjugation, attaching amine-bearing ligands to carboxylated polymers in water.

Biopolymer and hydrogel functionalisation

• A widely used reagent for amidation of hyaluronan and other carboxylated polysaccharides in water, grafting amines and reactive handles such as norbornene, methacrylate or tyramine onto the backbone; for hyaluronan ligation it has been reported to outperform EDC/NHS at equal feed ratio and to work without the pH-control sequence EDC/NHS requires.
• The modified polymers are crosslinked into hydrogels for tissue-engineering scaffolds, cell-culture matrices and biomaterials research, with DMTMM enabling an organic-solvent-free aqueous route.
• DMTMM is likewise applied to alginate, carboxymethyl cellulose and other carboxylated polysaccharides for amine, hydrazide or crosslinking chemistry in water.

Further Reading

For guidance on selecting between carbodiimides, aminium/uronium salts, phosphonium salts and other reagent classes for amide and peptide bond formation, see NorrChemica's Lab Journal guide: Choosing a Coupling Reagent for Amide and Peptide Bond Formation.