Antimicrobial Conjugated Oligoelectrolytes Containing Triphenylphosphonium Solubilizing Groups

Abstract

Conjugated oligoelectrolytes (COEs) are an emerging class of amphiphilic antimicrobial compounds with a modular molecular framework suitable for simple chemical derivatization. Here, a series of COE derivatives with a stilbene-conjugated segment and triphenylphosphonium (TPP) pendant groups was designed and synthesized to understand how lipophilic cationic groups impact antimicrobial activity. In vitro evaluations against ESKAPE pathogens showed broad-spectrum activity towards multi-drug resistant (MDR) bacteria and mycobacteria, with TPP groups enhancing antimicrobial activity towards clinically relevant Gram-nega-tive strains compared to their ammonium analogues. We studied the interactions of DM6P, the most active TPP-COE compound, with various membrane assays. Treatment of bacterial cells with DM6P showed enhanced permeability of cell membranes without inducing the development of significant bacterial resistance. Moreover, DM6P eliminated 99.99 % of methicillin-resistant Staphyloccocus aureus (MRSA) in an in vivo wound model. These results represent a promising chemical strategy for increasing the activity spectrum of membrane-active COE antibiotics to tackle challenging drug-resistant targets.

Real-Time Monitoring of Mitochondrial Damage Using Conjugated Oligoelectrolytes

“…The lipid bilayer-mimicking distribution of hydrophobic and hydrophilic domains promotes spontaneous membrane intercalation and environment-specific fluorescence emission. , These features distinguish COEs from other optical reporters that either associate with specific targets or are anchored to the lipid bilayer by hydrophobic domains . The high biocompatibility and tunable physicochemical and photophysical properties of MICOEs have allowed for biological applications, including labeling or killing microorganisms, − tracking extracellular vesicles, and cell imaging. − Despite these promising applications, little is known about the molecular features that influence interactions of COE with mammalian cells, particularly within subcellular organelles. In the case of COE-S6 , a representative cationic oligo-phenylenevinylene (oligo-PV) COE, previous colocalization studies demonstrated no mitochondrial association, instead it localizes exclusively within lysosomes upon cellular internalization, as illustrated in Scheme .…”