Refining AMOEBA Electrostatics for d -Glucose and 1→4-Linked d -Glucose Oligosaccharides

Abstract

Abstract Carbohydrate simulations are highly sensitive to the treatment of hydroxyl electrostatics because hydration, conformational sampling, and reactivity are governed by dense hydrogen-bonding networks. Here, we examine how oxygen quadrupole scaling affects AMOEBA d-glucose models generated with Poltype2 by comparing the standard 0.7 scaling with full 1.0 scaling for α- and β-d-glucose monosaccharides, 1→4-linked oligomers, and concentrated solutions. Increasing the oxygen quadrupole scaling from 0.7 to 1.0 improves monosaccharide hydration free energies, increases d-glucose–water hydrogen-bond counts and lifetimes, and strengthens hydroxyl electric-field projections without substantially altering hydration-shell structure. In 1→4-linked d-glucose oligomers, full scaling also enhances intramolecular hydrogen bonding, restricts conformational sampling, and produces more organized chain electrostatics. Electric-field decompositions indicate that OH2 and OH3 in α1→4 d-glucose oligomers are strongly coupled to intramolecular hydrogen-bond networks, whereas OH6 remains more water-controlled and solvent-accessible. Diffusion simulations show that both models perform reasonably well at concentrations up to 0.5 mol/kg but overestimate the slowdown of d-glucose mobility at higher concentrations, especially with 1.0 scaling. Overall, full oxygen quadrupole scaling improves local hydration, hydroxyl electrostatics, and diffusion behavior in the lower-concentration regime. Further refinement is needed to balance these stronger interactions against transport properties in highly concentrated carbohydrate solutions, which may be particularly relevant to materials applications.