Unveiling the potent activity of a synthetic ion transporter against multidrug-resistant Gram-positive bacteria and biofilms.

The increasing prevalence of drug-resistant infections caused by Gram-positive bacteria poses a significant threat to public healthcare. These pathogens exhibit not only smart resistance mechanisms but also form impenetrable biofilms on various surfaces, rendering them resilient to conventional therapies. In this study, we present the potent antibacterial activity of a synthetic ion transporter T against multi-drug resistant (MDR) Gram-positive pathogens, with minimum inhibitory concentration (MIC) values ranging from 0.5 to 2 µg mL-1. The compound demonstrates high selectivity with negligible toxicity towards mammalian cells (HC50 = 810 µg mL-1). It exhibits fast killing kinetics, completely eliminating >5 log bacterial cells within 12 h. Moreover, the compound displays efficacy against both planktonic bacteria and preformed biofilms of methicillin-resistant S. aureus (MRSA), reducing the bacterial burden within the biofilm by 2 log. Mechanistic investigations reveal that the ion transporter depolarizes the bacterial membrane potential and enhances membrane permeability. Additionally, it generates reactive oxygen species, contributing to its bactericidal activity. Notably, MRSA did not exhibit detectable resistance to the ion transporter even after serial passaging for 10 days. Collectively, this novel class of ion transporter holds promise as a therapeutic candidate for combating infections caused by multi-drug resistant Gram-positive bacteria.

Transmembrane H+/Cl- cotransport activity of bis(amido)imidazole receptors.

A series of sickle-shaped bis(amido) imidazoles are synthesized for their ion transport studies. Proton-anion binding by the neutral and protonated form of receptors assessed by 1H-NMR titration experiments confirmed better chloride binding by the protonated form of a receptor compared to its neutral form. The transport experiments across unimolecular vesicles (by HPTS and lucigenin assays) confirmed the H+/Cl- symport process under the applied pH gradient conditions. The transporter also allows anion antiport as evident from the studies under symmetrical pH conditions. The ionophoric activity by the mobile carrier mechanism is proved by the U-tube experiment.

An anion receptor that facilitates transmembrane proton-anion symport by deprotonating its sulfonamide N-H proton.

Indole-based amide-sulfonamide derivatives were synthesized. The X-ray crystal structure and chloride binding studies in solution showed a 1 : 1 stoichiometry. The ion transport efficiency directly correlated to the pKa of the sulfonamide N-H protons. The mechanistic study indicated proton-anion symport across the lipid bilayer membrane.

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity.

Acyclic αγα-tripeptides derived from fluorinated-furanoid sugar amino acid frameworks act as reverse-turn inducers with a U-shaped conformation, whereas the corresponding nonfluorinated αγα-tripeptides show random peptide conformations. The NMR studies showed the presence of bifurcated weak intramolecular hydrogen bonding (F···HN) and N+···Fδ- charge-dipole attraction compel the amide carbonyl groups to orient antiperiplanar to the C-F bond, thus, demonstrating the role of the fluorine substituent in stabilizing the U-shaped conformation. The NOESY data indicate that the U-shaped tripeptides self-assembly formation is stabilized by the intermolecular hydrogen bonding between C═O···HN with antiparallel orientation. This fact is supported by ESI-MS data, which showed mass peaks up to the pentameric self-assembly, even in the gas phase. The morphological analysis by FE-SEM, on solid samples, showed arrangement of fibers into nanorods. The antiparallel self-assembled pore of the fluorinated tripeptides illustrates the selective ion-transport activity. The experimental findings were supported by DFT studies.

A Dimeric Bis(melamine)-Substituted Bispidine for Efficient Transmembrane H+ /Cl- Cotransport.

A 3,7-diazabicyclo[3.3.1]nonane linking to two melamines is a unique transmembrane H+ /Cl- carrier. In the solid state, the V-shaped compound forms a HCl-bound zig-zag network through cooperative protonation and hydrogen bond interactions. In the lipid membrane, the receptor forms a dimeric self-assembly involving multiple H+ and Cl- leading to the efficient transport of the acid. The pH-dependent Cl- efflux observed for the compound was rationalized based on a gradual protonation model that confers an active transmembrane carrier at physiological pH.

Selective Sensing of Metal Ions and Nitro Explosives by Efficient Switching of Excimer-to-Monomer Emission of an Amphiphilic Pyrene Derivative.

An amphiphilic pyrene derivative exhibiting unusually stable excimer emission due to strong aggregation is presented. The aggregated system served as an intelligent sensor for metal ions and nitro explosives in aqueous media. The excimer displayed excellent selectivity toward Cu2+ among the tested cations. The observation was interpreted on the basis of chelation of metal ions involving the hydroxyl and amino groups of two molecules, leading to the ligand-to-metal charge-transfer (CT) process. The excimer was further applied for the cell imaging of Cu2+ ions. Also, while treating the excimer with various nitro explosives, it displayed efficient 2,4,6-trinitrophenol sensing, corroborating mainly the CT process from pyrene to the analyte due to intercalation of the analyte within pyrene.