An exploration of the solvent- and acid-catalyzed mutarotation mechanisms of lactose in aqueous solution

• Published in: New journal of chemistry 2020-10, Vol.44 (38), p.16421-1643
• Main Authors: Chen, Zeqin, Wu, Tunyan, Yang, Xue, Yue, Fen, Fu, Fengping
• Format: Article
• Language: English
• Subjects: Acetic acid; Acids; Activation energy; Aqueous solutions; Carbohydrates; Cartesian coordinates; Inhalers; Isomerization; Lactose; Milk; Pharmaceuticals; Potential energy; Protonation; Ring opening; Ring structures; Solvents; Water chemistry
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d0nj03660a

Lactose, the characteristic carbohydrate of milk, is a high-value product applied as an excipient in pharmaceutical formulations and as a carrier in dry-powder inhalers when purified. Usually, lactose is in the mutarotation equilibrium of two anomers in solution, the α and the β forms. This work has dealt theoretically with the mutarotation mechanisms of α-lactose catalyzed by solvent water molecules and acid molecules, including acetic acid (HAc) and trifluoroacetic acid (TFA). The whole mutarotation process is comprised of three stages, i.e. , the initial ring-opening step, the isomerization of anomeric carbon C1 followed by the ring-closing step, in which, the ring-opening step involves the highest activation energy and therefore is the rate-determining step. The activation energies along the optimum mutarotation routes catalyzed by H 2 O, HAc and TFA molecules are 22.1, 13.5 and 8.7 kcal mol −1 , respectively. All the transition states involved in the optimum ring-opening/closing reaction coordinates are octatomic ring structures with the presence of two solvent water molecules or one acid molecule. For the acid-catalyzed rate-determining step, the reaction driving force originates from the protonation of the sugar ring O5 atom by the carboxyl hydrogen atom, whereas for the solvent-catalyzed process, it originates from the transfer of C1-hydroxyl hydrogen. The ease of lactose mutarotation depends greatly on the acidity of the catalyst. The obtained observation can provide more valuable information for pharmaceutical science. Exploration of the solvent- and acid-catalyzed mutarotation mechanisms of lactose to reveal the ease of the mutarotation varying with the acidity of the catalyst.