Design, synthesis, and bioactivity evaluation of PABA-based five- and six-membered heterocyclic Schiff base quaternary ammonium chitosan derivatives

Abstract

This study reports the green and efficient synthesis of two novel categories of quaternary ammonium chitosan derivatives via ion-exchange, aiming to enhance their biological activities and expand potential applications. Para-aminobenzoic acid (PABA) was reacted with five- and six-membered heteroaromatic aldehydes to form Schiff bases, which were ionized and introduced into two types of quaternary ammonium chitosan: N-(2-hydroxypropyl) trimethylammonium chloride chitosan (HACC) and N, N, N-trimethyl chitosan iodide (TMCI). by replacing chloride and iodide ions. The structures and physicochemical properties of the derivatives were characterized using FTIR, ¹H NMR, TGA, and XRD. Their antioxidant and antibacterial activities were systematically evaluated. Results showed that the incorporation of PABA-based Schiff bases significantly improved both activities in the HACC and TMCI systems, suggesting a synergistic effect. Cytotoxicity (CCK-8 assay) and hemolysis tests demonstrated that the derivatives exhibited excellent biocompatibility and caused no red blood cell lysis within the tested concentration range. Overall, the introduction of PABA-based Schiff bases effectively enhanced the bioactivity and biosafety of quaternary ammonium chitosan, providing a promising foundation for their application in antibacterial, antioxidant, and biomedical materials.

Keywords: Bioactivity; Chemical modification; Chitosan; PABA-Schiff Base.