The role of protonation and solvation in modulating the electronic structure in α- and β-D-glucosamine: A density functional theory study

Abstract

Glucosamine is a biologically relevant amino sugar that plays a key role in glycoproteins and polysaccharides such as chitin and chitosan. Despite its importance, a detailed quantum-level understanding of the electronic and conformational behavior of its α- and β-anomers under varying protonation and hydration conditions remains limited. Herein, we present a comprehensive DFT study at the B3LYP/6-31+G(d,p) level, modeling α- and β-D-glucosamine in both neutral and protonated forms with explicit hydration (1–5 water molecules). Our results show that neutral β-glucosamine is energetically more stable than its α-counterpart by 0.61 kcal/mol, consistent with its predominance in aqueous solution. Protonation induces significant electronic redistribution, with the LUMO localizing around the NH₃⁺ group and the HOMO shifting away from it. This leads to a marked increase in the HOMO–LUMO energy gap, from 6.37 kcal/mol (neutral α-form) to a maximum of 7.32 kcal/mol (protonated β-form with 4H₂O), indicating enhanced electronic stability and decreased reactivity. Explicit solvation stabilizes key hydrogen bond networks, with H-bond lengths as short as 1.51 Å in protonated systems. These findings offer new insight into how solvation and protonation shape the electronic landscape of glucosamine, with implications for its behavior in biological systems, material design, and protonation-dependent reactivity. The novelty of this study lies in combining explicit microsolvation with frontier orbital and MEP analysis across protonation states of both anomers—a previously unexplored approach.