Supramolecular Nanochannels: Suprasome-Mediated Delivery of Ionophore to Regulate Transmembrane Zn²⁺ Ion Transport

The development of synthetic ion channels and stimuli-responsive suprasomes represents two crucial yet largely disconnected areas of supramolecular chemistry. Herein, we demonstrated that suprasomes can effectively deliver hydrophobic synthetic ion transporters to lipid membranes, regulating physiologically significant transition metal ions and subsequently modulating activity within lipid-bound compartments. We showed that a potent bis(vinylbenzimidazole)phenol derivative self-assembles within the lipid bilayer to form a supramolecular nanochannel, which facilitates selective and efficient transport of Zn²⁺ ions from the external aqueous solution across the lipid bilayer and into the internal solution of large unilamellar vesicles via an electrogenic pathway. The hydrophobic ion transporter could also be delivered to lipid bilayers due to its inherent ability to form suprasomal assembly with β-cyclodextrin (β-CD) through dynamic host-guest interactions. The Zn²⁺ ions serve as stimuli to disassemble the suprasomes and release the ion transporter, which further penetrates the bilayers of lipid vesicles and regulates transmembrane Zn²⁺ ion transport. The application of this strategy of stimuli-mediated delivery of synthetic ion transporters to regulate transmembrane Zn²⁺ ion transport showed antibacterial activities against Gram-positive, Gram-negative, and drug-resistant bacterial cells.