Conjugation of 2-oxazoline copolymers with acyclic and macrocyclic chelating compounds of polyamino polycarboxylic structure

In this work, we introduce a new synthetic pathway to obtain conjugates of poly(2-oxazoline)s (POx) and chelating agents (CA), applying the triazine-based coupling compound. Conjugates based on 2-ethyl- (EtOx) and 2-(3-butenyl)-2-oxazoline (ButEnOx) copolymers coupled with acyclic and macrocyclic chelating compounds: diethylenetriaminepentaacetic acid (DTPA) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were obtained (POx-DTPA or POx-DOTA). Nuclear magnetic resonance spectra are presented. By the modification, the ability for complexation of ions have been imparted to the macromolecules. Studies on the uptake of various cations (including these stabilizing outer membrane (OM) of Gram-negative bacteria) at different environmental pH for POx-DTPA and POx-DOTA are presented. Also, the energy dispersive X-ray (EDX) spectra and X-ray photoelectron spectra (XPS) are shown. The analysis of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) with the use of Gram-negative strains E. coli and P. aeruginosa has shown that conjugates exhibit bactericidal properties. The cytometric analysis revealed permeability of bacterial OM after POx-DOTA treatment, comparable to low-molecular weight chelator EDTA known from its bactericidal properties, or even better than EDTA in case of POx-DTPA. In addition to antibacterial activity, the systems remained non-toxic to human fibroblasts in a wide range of concentrations, making them promising for further fundamental studies on antibacterial polymers.The following files are deposited in the repository: the energy dispersive X-ray (EDX) spectra of the conjugates complexed with metal ions, nuclear magnetic resonance (NMR) spectra of the conjugates, SEC chromatograms (RI and LS signal) of the conjugates, bacterial cell membrane permeability test results (RFU and Flow cytometry analysis), cytotoxicity assay results.