Interactions of a Paracyclophane-based Conjugated Oligoelectrolyte with Biological Membranes

A three-dimensional conjugated oligoelectrolyte (COE), COE2-3-pCp, was synthesized to study its effects on lipid bilayers. Its structure evolved from previously reported planar COEs via the incorporation of [2.2]paracyclophane within the delocalized central unit thus introducing an additional dimension to molecular format. The biological activity of COE2-3-pCp, in particular its insertion into and effects on biological membranes, was determined using both in vitro and molecular dynamic simulation techniques relative to its planar counterpart (COE2-3C). COE2-3-pCp induced higher lipid disorder, but without marked antimicrobial activity. In addition, COE2-3-pCp permeabilized lipid vesicles and cell membranes to an extent similar to that of COE2-3C. Combined, the data suggest that the non-inhibitory nature of COE2-3-pCp may result from a lower tendency to aggregate in the bilayer revealing that toxicity can be decoupled from membrane permeabilizing activity. Hence, subsequent generations of COEs may be designed to maximize membrane permeabilization while maintaining good biocompatibility for applications in whole-cell biocatalysis