Structure-property relationships in phenolic acid-chitosan complexes: From molecular interactions to multifunctional bioactivities.
Phenolic acid-chitosan complexes combine the antioxidant capacity of phenolic acids with the antibacterial activity of chitosan; however, their study has received limited attention due to challenges in synthesis. In this work, a selection of phenolic acids-4-hydroxybenzoic acid (HA), protocatechuic acid (PA), vanillic acid (VA), and ferulic acid (FA)-were complexed with chitosan in aqueous medium under thermal treatment. Elevated temperature markedly improved the solubility of phenolic acids, thereby enhancing complexation efficiency. XPS N 1 s analysis revealed that the balance between Free-NH₂ and ionic -NH₃+ is influenced by phenolic acid structure: phenolic hydroxyl groups promote ionic bonding, whereas methoxy groups hinder effective interaction due to hydrophobicity and steric bulk. This molecular-level programming translates into distinct macroscopic properties. The thermal stability and surface wettability of the complexes correlate with the ionic -NH₃+ content, while emulsifying performance, antioxidant capacity, antibacterial activity, and cytotoxicity are primarily governed by the intrinsic structural features of the phenolic acid ligands-such as the number of hydroxyl groups, the presence of methoxy substituents, and conjugated side chains. At concentrations relevant to antibacterial application (1.25-2.5 mg/mL), all complexes maintained >75% cell viability, indicating acceptable biocompatibility within the intended concentration range. These findings suggest a structure-property relationship in which phenolic acid substituents influence the interaction mode with chitosan and thereby affect the resulting physicochemical and biological properties. The thermal-assisted synthesis offers a simple, catalyst-free route to these multifunctional complexes, positioning them as promising candidates for applications in food preservation and related fields.