Substituent-directed degradation mechanisms of glucose derivatives under UV/H₂O₂ treatment: Integrated experimental and theoretical insights

The radical-mediated degradation of polysaccharides is a promising route to modify their bioactivity, but the fundamental role of side-chain substituents in directing these reactions remains unclear. Therefore, this study systematically investigated the influence mechanisms of substituents on the monosaccharide degradation under UV/H₂O₂ treatment. Six glucose derivatives, including d -glucose, D-gluconic acid, methyl-D-glucopyranoside, D-glucal, D-glucosamine, and D-glucono-δ-lactone, were selected to represent typical electron-donating (-OCH₃, -NH₂), electron-withdrawing (-COOH, -C=O), and unsaturated double bond (C=C) groups. Degradation kinetic analysis revealed that electron-donating groups accelerated the radical degradation (k obs  = 31.59 × 10 −3  min −1 for D-glucal), while electron-withdrawing groups decelerated it (k obs  = 17.50 × 10 −3  min −1 for D-gluconic acid). The formation of carbonyl and carboxyl groups showed distinct accumulation patterns dependent on the substituent. Product profiling via high-performance anion exchange chromatography coupled with tandem electrospray mass spectrometry (HPAEC-ESI-MS/MS) demonstrated unique fragment patterns for each derivative, confirming substituent-directed reaction pathways. Quantum chemistry calculations further validated the proposed mechanisms, showing that electron-donating groups lowered the energy barriers for key steps such as hydrogen abstraction and peroxyl-radical cleavage. This work elucidates that the electronic properties of side-chain substituents determine the regioselectivity, kinetics, and product distribution in monosaccharide radical degradation. The findings provide a foundational mechanistic framework for predicting and controlling the degradation of complex functional polysaccharides.