1H NMR studies of molecular interaction of d-glucosamine and N-acetyl-D-glucosamine with curcumin and caffeic acid phenethyl ester in DMSO

Abstract

Chitosan (Cs)-based polymers have been explored as potential drug-delivery systems that could enhance the practical applications of bioactive phenolic (Ph) substances, such as curcumin (CUR) and caffeic acid phenethyl ester (CAPE). In this study, we focused on designing CS-based drug carriers by examining the intermolecular interactions between the polymer components, d-glucosamine (Gn) and N-acetyl-d-glucosamine (AGn), and the target substances CUR and CAPE through ¹H NMR titration in dimethyl sulfoxide (DMSO‑d₆). The observed changes in chemical shifts indicated that Gn cation (GnH⁺) forms molecular complexes, whereas AGn does not exhibit any intermolecular interaction. We developed a titration curve for the complexation, which competes with the self-association of GnH⁺ (Gn_z) in DMSO. Least-squares analyses concluded that molecular complex represented as Ph·Gn_z (z = 3 or 4) is formed through a reaction between a Gn_z aggregate and a Ph molecule. The formation constant, K = [Ph·Gn_z]/[Ph][Gn_z], falls within the range of 50–300 M⁻¹. The complex is stabilized by intermolecular interactions at multiple sites within the glucosamine aggregate Gn_z, although the non-covalent interactions at each binding site are relatively weak. These findings suggest that chitosan can capture CAPE or CUR exclusively at segments composed of adjacent cationic glucosamine units.