Electronic Analysis of Intermolecular Interactions in Hexose Crystals

Abstract

Although all hexoses share the molecular formula C₆H₁₂O₆, differences in hydroxyl group orientation lead to pronounced variations in crystal packing and hydrogen-bond networks. However, a systematic, site-resolved electronic comparison of intermolecular hydrogen bonding across hexose crystals remains limited. To clarify the electronic features of intermolecular hydrogen bonding, we investigated 13 hexoses using DV-Xα molecular orbital calculations on cluster models constructed from single-crystal structures (CSD and in-house determinations). Hydrogen-bond strength was evaluated by the bond overlap population (BOP), and Full Interaction Maps (FIMs) analysis was performed for β-aldohexoses. BOP analysis showed that the anomeric O1 site gives the largest values in β-aldohexoses, whereas no distinct site preference appears in α-aldohexoses; in contrast, O1 shows the smallest values in ketohexoses. Combined BOP and FIMs analyses indicate that both the strength and site selectivity of intermolecular hydrogen bonding are governed by steric features arising from molecular structure. FIMs analysis further demonstrated that hydrogen-bond formation depends not only on electronic strength but also on spatial arrangement. The present findings provide a quantitative, site-resolved basis for understanding monosaccharide crystal structures and support rational design of rare-sugar-based functional materials by linking hydrogen-bond electronics with packing geometry.