Issue 9, 2016

Influence of molecular structure on the antimicrobial function of phenylenevinylene conjugated oligoelectrolytes

Abstract

Conjugated oligoelectrolytes (COEs) with phenylenevinylene (PV) repeat units are known to spontaneously intercalate into cell membranes. Twelve COEs, including seven structures reported here for the first time, were investigated for the relationship between their membrane disrupting properties and structural modifications, including the length of the PV backbone and the presence of either a tetraalkylammonium or a pyridinium ionic pendant group. Optical characteristics and interactions with cell membranes were determined using UV-Vis absorption and photoluminescence spectroscopies, and confocal microscopy. Toxicity tests on representative Gram-positive (Enterococcus faecalis) and Gram-negative (Escherichia coli) bacteria reveal generally greater toxicity to E. faecalis than to E. coli and indicate that shorter molecules have superior antimicrobial activity. Increased antimicrobial potency was observed in three-ring COEs appended with pyridinium ionic groups but not with COEs with four or five PV repeat units. Studies with mutants having cell envelope modifications indicate a possible charge based interaction with pyridinium-appended compounds. Fluorine substitutions on COE backbones result in structures that are less toxic to E. coli, while the addition of benzothiadiazole to COE backbones has no effect on increasing antimicrobial function. A weakly membrane-intercalating COE with only two PV repeat units allowed us to determine the synthetic limitations as a result of competition between solubility in aqueous media and association with cell membranes. We describe, for the first time, the most membrane disrupting structure achievable within two homologous series of COEs and that around a critical three-ring backbone length, structural modifications have the most effect on antimicrobial activity.

Graphical abstract: Influence of molecular structure on the antimicrobial function of phenylenevinylene conjugated oligoelectrolytes

Supplementary files

Article information

Article type
Edge Article
Submitted
10 Feb 2016
Accepted
28 May 2016
First published
01 Jun 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 5714-5722

Influence of molecular structure on the antimicrobial function of phenylenevinylene conjugated oligoelectrolytes

H. Yan, Z. D. Rengert, A. W. Thomas, C. Rehermann, J. Hinks and G. C. Bazan, Chem. Sci., 2016, 7, 5714 DOI: 10.1039/C6SC00630B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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