Tailoring the antioxidant activity of Zn(II)(acylpyrazolone)-doped chitosan films through structural modification of the zinc coordination environment

The synthesis and application of a new series of Zn(II) acylpyrazolonate complexes as antioxidant additives for chitosan (CS)-based films are herein reported. Homoleptic [Zn(QPhR)₂(solv)ₙ] (R = -tBu, 1; NO₂, 2; F, 3; CF₃, 4) compounds and heteroleptic [Zn(QPhR)(pic)Cl] (5–8; pic = 2-picolylamine) derivatives were designed to modulate the electronic and steric properties of the ligands and the coordination environment around the Zn(II) center. Single-crystal X-ray diffraction of 2, 4, 7 and 8 revealed distinct coordination geometries, enabling structure–property correlations. Complexes 1, 2, 4, 7, and 8 were incorporated at variable loadings (1.25–10% w/w) into CS via solvent casting to afford CS@ZnXn films. PXRD analyses of the films indicated that additive miscibility within the polymer matrix depends on both concentration and ligand substituents, with polar groups promoting higher amorphization and film homogeneity. All complexes exhibited significant DPPH radical scavenging activity in solution, modulated by ligand substitution and coordination features. The antioxidant activity was retained after incorporation into CS and showed concentration-dependent behavior, although polymer–complex interactions influenced the efficiency in the solid state. Preliminary in vitro hepatotoxicity studies using a membrane-based hepatic model indicated overall good biocompatibility, with limited impact on metabolic activity at early exposure times. These findings demonstrate that Zn(II) acylpyrazolonate complexes represent promising multifunctional additives for the development of antioxidant CS-based materials for active packaging applications.