Chelate-functionalized poly(2-oxazoline) for the destruction of bacterial cell membranes†

In this work we study the conjugate of the copolymer of 2-substituted-2-oxazolines and a chelating compound, which may potentially entrap the ions responsible for stabilizing the bacterial outer membrane (OM). The proposed strategy demonstrates a new approach to synthesize antibacterial polymers and redefines the possibilities of their interactions with bacteria. Here, we imparted chelating ability to a 2-ethyl-2-oxazoline and 2-(3-butenyl)-2-oxazoline copolymer (POx) by its modification with the 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA) chelating agent. The obtained conjugate (POx-DOTA) was carefully characterized and its structure has been proved. It was shown that POx-DOTA formed nanostructures in aqueous solutions and exhibited the ability to complex with Ca²⁺ ions. The interactions between POx-DOTA and E. coli were visualized using TEM microscopy, which revealed that the conjugate was capable of destroying the bacterial cell membrane leading to its disintegration. At the same time, the number of bacterial cell colonies in the presence of POx-DOTA did not increase throughout the culture, which means that the studied polymer system exhibited bacteriostatic properties. Obtaining new 2-substituted-2-oxazoline-based polymers functionalized with chelates, capable of interacting and destroying bacterial cell membranes, may be a new solution for achieving effective materials with antibacterial activity.