Repurposing host-guest chemistry to sequester virulence and eradicate biofilms in multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii.

The limited diversity in targets of available antibiotic therapies has put tremendous pressure on the treatment of bacterial pathogens, where numerous resistance mechanisms that counteract their function are becoming increasingly prevalent. Here, we utilize an unconventional anti-virulence screen of host-guest interacting macrocycles, and identify a water-soluble synthetic macrocycle, Pillar[5]arene, that is non-bactericidal/bacteriostatic and has a mechanism of action that involves binding to both homoserine lactones and lipopolysaccharides, key virulence factors in Gram-negative pathogens. Pillar[5]arene is active against Top Priority carbapenem- and third/fourth-generation cephalosporin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, suppressing toxins and biofilms and increasing the penetration and efficacy of standard-of-care antibiotics in combined administrations.

The "Nitrogen Effect": Complexation with Macrocycles Potentiates Fused Heterocycles to Form Halogen Bonds in Competitive Solvents.

Weak intermolecular forces are typically very difficult to observe in highly competitive polar protic solvents as they are overwhelmed by the quantity of competing solvent. This is even more challenging for three-component ternary assemblies of pure organic compounds. In this work, we overcome these complications by leveraging the binding of fused aromatic N-heterocycles in an open resorcinarene cavity to template the formation of a three-component halogen-bonded ternary assembly in a protic polar solvent system.

Divalent Benzimidazolium-Based Axles for Self-Reporting Pseudorotaxanes.

Mono- and (bis)benzimidazoliums were evaluated both experimentally and computationally for their potential as pseudopolyrotaxane axle building blocks. Their aggregation and photophysical behavior, along with their potential to form a [2]pseudorotaxane with dibenzyl-24-crown-8, was studied through the synergistic application of 1D/2D and diffusion-ordered NMR spectroscopy, mass spectrometry, ultraviolet-visible and fluorescence spectroscopy, and time-dependent density functional theory. Their photophysical behavior was measured and modeled as a function of protonation state, solvent, and concentration.

Naphthalene-functionalized resorcinarene as selective, fluorescent self-quenching sensor for kynurenic acid.

Kynurenic acid is a by-product of tryptophan metabolism in humans, with abnormal levels indicative of disease. There is a need for water-soluble receptors that selectively bind kynurenic acid, allowing for detection and quantification. We report here the high-affinity binding of kynurenic acid in aqueous media to a resorcinarene salt receptor decorated with four flexible naphthalene groups at the upper rim.