Local Site Selectivity and Conformational Structures in the Glycosidic Bond Scission of Cellobiose

Car–Parrinello molecular dynamics combined with metadynamics simulations were used to study the acid-catalyzed hydrolysis of cellobiose (CB) in aqueous solution. The hydrolysis was studied in two steps. Step 1 involves the proton transfer from solvent to CB and dissociation of the glycosidic bond to β-glucose and oxacarbenium ion species. Step 2 involves the formation of α-glucose from oxacarbenium and regeneration of the acid proton species. Step 1 is endothermic, while Step 2 is exothermic. The overall activation free energy of CB hydrolysis is 32.5 kcal mol–1, and the overall reaction free energy is −5.9 kcal mol–l, consistent with available experimental data. We observe that a stepwise mechanism generally described in the literature for Step 1 is not significantly favored relative to a concerted β-1,4′ linkage dissociation process.