We report a rationally designed membrane‐intercalating conjugated oligoelectrolyte (COE), namely COE‐IC, which endows aerobic N2‐fixing bacteria Azotobacter vinelandii with a light‐harvesting ability that enables photosynthetic ammonia production. COE‐IC possesses an acceptor‐donor‐acceptor (A‐D‐A) type conjugated core, which promotes visible light absorption with a high molar extinction coefficient. Furthermore, COE‐IC spontaneously associates with A. vinelandii to form a biohybrid in which the COE is intercalated within the lipid bilayer membrane. In the presence of L‐ascorbate as a sacrificial electron donor, the resulting COE‐IC/A. vinelandii biohybrid showed a 2.4‐fold increase in light‐driven ammonia production, as compared to the control. Photoinduced enhancement of bacterial biomass and production of L‐amino acids is also observed. Introduction of isotopically enriched 15N2 atmosphere led to the enrichment of 15N‐containing intracellular metabolites, consistent with the products being generated from atmospheric N2.

No 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.

We report a rationally designed membrane‐intercalating conjugated oligoelectrolyte (COE), namely COE‐IC, which endows aerobic N2‐fixing bacteria Azotobacter vinelandii with a light‐harvesting ability that enables photosynthetic ammonia production. COE‐IC possesses an acceptor‐donor‐acceptor (A‐D‐A) type conjugated core, which promotes visible light absorption with a high molar extinction coefficient. Furthermore, COE‐IC spontaneously associates with A. vinelandii to form a biohybrid in which the COE is intercalated within the lipid bilayer membrane. In the presence of L‐ascorbate as a sacrificial electron donor, the resulting COE‐IC/A. vinelandii biohybrid showed a 2.4‐fold increase in light‐driven ammonia production, as compared to the control. Photoinduced enhancement of bacterial biomass and production of L‐amino acids is also observed. Introduction of isotopically enriched 15N2 atmosphere led to the enrichment of 15N‐containing intracellular metabolites, consistent with the products being generated from atmospheric N2.

Triphenylphosphonium functionalization of a conjugated oligoelectrolyte (COE) with a stilbene core improved its spectrum of activity to include ESKAPE pathogens and mycobacteria while crucially retaining the membrane‐perturbing mode of action characteristic of COEs. The efficacy of the lead compound in vivo highlights the potential of the COE molecular platform for designing more effective antibiotics. More information can be found in the Research Article by G. C. Bazan and co‐workers (DOI: 10.1002/chem.202203803).