Mechanochemistry-Assisted Fabrication of (Carboxymethyl)cellulose Mediated by Minute Surface-Confined Water

The current manufacture of (carboxymethyl)cellulose (CMC) requires a large amount of solvents, severely resulting in environmental impacts and a laborious separation process. Herein, a “green” synthetic route employing a mechanochemistry strategy was addressed to prepare CMC promoted by minute surface-confined water. The mechanical forces (shear and strain) from ball collisions facilitated the formation of disordered regions, promoting the water-holding capacity of cellulose. Together, water molecules permeated the impact structure and were locked by surface hydroxyls, intensifying the chemical accessibility. The resultant CMC possessed a wide degree of substitution within 0.38–1.03 and a maximum yield of 46.1% under optimal mechanochemical conditions. Density functional theory revealed that Gibb’s free energy (ΔGTS) of hydroxyl activation was approximately −1.73 eV on the surface of dry cellulose. In comparison, ΔGTS was reduced to −3.37 eV upon intervention of water. The reactivity sensitivity of hydroxyls was C2 > C6 > C3 on the surface of highly hydrated cellulose. The high concentration (1200 μg/mL) of CMC was not significantly toxic to HepG2 cells (apoptosis rate of less than 4.0%), demonstrating the excellent biocompatibility of CMC prepared by this strategy. This mechanochemical method opened a safe and environmentally friendly avenue to produce CMC without sacrificing excess reagents.