A Novel Approach to POx-chelate Conjugates and Comparison of Their Antibacterial Activity with POx Systems Containing Amino Groups

Abstract

This study presents a novel synthetic strategy for the preparation of antibacterial poly(2-oxazoline)-based (POx) conjugates with chelating agents. A well-defined random copolymer of 2-ethyl-2-oxazoline and 2-[N-Boc-5-aminopentyl]-2-oxazoline was synthesized via microwave-assisted cationic ring-opening polymerization (CROP). Following deprotection, the copolymer was conjugated with diethylenetriaminepentaacetic acid (DTPA). This work demonstrates a simplified and efficient route to antibacterial POx conjugates, in which amino groups are obtained after polymerization and directly coupled to a chelator. No post-polymerization modification of the polymer is required to generate amino groups in the substituents. A comprehensive characterization of both the conjugated POx and its amino-modified precursor was carried out, including structural analysis and physicochemical properties. Preliminary antibacterial activity and cytotoxicity were assessed, including bacterial membrane assays and microscopic imaging. Both systems exhibited activity against E. coli, a commonly used representative Gram-negative strain; however, they act via different mechanisms: the conjugate likely through cation chelation, and its amino-modified precursor through cationic polymer-mediated interactions. Importantly, both polymers were cytocompatible with human fibroblasts. Overall, this study establishes a versatile platform for designing polymeric antimicrobial agents, offering tunable ion-chelating functionality for future biomedical applications.