Stimuli Responsive Small Molecule Anion Transporters

Abstract

The transport of ions across the lipid bilayer is controlled by ion transport proteins. There are numerous synthetic ion transporters developed to date and some of these have shown promises to target certain life-threatening diseases. However, most of these molecules always remain active and fail to discriminate between diseased and healthy cells. Therefore, we have developed small-molecule pro-carriers which can be activated only by either external stimuli such as light or cell-specific chemical stimuli such as pH. These molecules were designed to facilitate chloride transport only after forming corresponding active transporters triggered by these stimuli. For this purpose, indole-based pro-carriers were designed for forming the active carrier by light. Bispidine-based molecules were designed for forming active carriers only under acidic pH and then facilitating chloride transport. From NMR titration studies, indole-based active transporters were found to bind to chloride ions efficiently. Transport of chloride ions across lipid bilayer was established by the lucigenin assay. The mechanism of ion transport determined by cooperative valinomycin (a K+ carrier) assay showed the antiport mechanism. Pro-carriers were inactive because the anion binding site was blocked by a photocleavable group. For the bispidine-based system, the synthesis and characterization of molecules are done. In future, the photocleavage of the protecting group from indole-based pro-carriers and pH-dependent ion transport by bispidine-based molecules would be carried out.