A chloride-responsive molecular switch: driving ion transport and empowering antibacterial properties

Abstract

A molecular switch was developed to recognize and transport Cl⁻ across lipid bilayers. The XRD-crystal structure and NOESY NMR spectra of a potent 4-aminoquinazoline analogue confirmed Cl⁻-induced conformation changes. Systematic biophysical studies revealed that the quinazoline moiety forms cooperative interactions of H⁺ and Cl⁻ ions with the thiourea moiety, resulting in the transport of H⁺/Cl⁻ across the membranes. A pH-dependent analysis revealed that the transport of Cl⁻ by the potent compound increased in an acidic environment. The potent compound could also transport H⁺/Cl⁻ across Gram-positive bacteria, leading to antibacterial activities.