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

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.