Design and Fabrication of Small Molecule-Based Supramolecular Systems for the Selective Transmembrane Transport of Ions

Abstract

The biological lipid membrane encloses cellular components and cell organelles in protective layers and does not allow the permeation of highly polar solutes. However, the proper operation of cellular functions depends on the passage of many polar solutes across cellular membranes, such as cations, anions, water, amino acids, ATP, and carbohydrates. Integral membrane proteins, such as channels, carriers, and pores, disintegrate hydrophobic barriers in phospholipid bilayer membranes to facilitate their permeation. This mechanism, essential for the disbursement of information stored in the components that make up cells, is required for processes like cell division, cellular signalling, pH and osmotic pressure regulation, etc. Because of the substantial studies that have been carried out on their structures and modes of action, chemists have created artificial systems that imitate their natural congeners. Two of the most prevalent and necessary natural ions in the physiological systems are potassium and chloride, which are transported via ion pumps, ion carriers, or membrane-embedded protein channels. The potassium ion plays an important role in cell membrane physiology and helps regulate fluid balance, muscle contractions and nerve signals. The chloride ion maintains ion homeostasis by regulation of pH, maintenance of intracellular volume, resting membrane potential and cell growth. Mutations in the natural protein channels can result in a number of fatal disorders such as Cystic fibrosis, Bartter syndrome, Dent’s disease, Hypokalaemia, etc. Here, we have presented various methods to fabricate supramolecular systems which can facilitate the selective transport of cations, anions or the symport of both cations and anions in a non-gated approach. In the first part of the work, we have discussed a supramolecular approach for constructing non-gated 1,2,3-triazole-based ion carriers that perform transmembrane transport via anion antiport and act as efficient nontoxic chloride transporters at elevated concentrations that can expedite potential therapeutic studies including replacement of defective chloride channels using ‘channel replacement therapy’. Subsequently, we moved on to design a series of quinoline-based transporters that exhibited an electrogenic K/H. These are some of the rare examples of quinoline moieties that employ the oxygen atoms of the amide and the hydroxyl groups to bind to and facilitate the selective transport of the potassium cation. Subsequently, we focussed on the design of a series of mandelic acid-based small-molecule channels which showed significant K/Clselectivity during transmembrane transport. Intriguing crystal structures were also a highlight of this part of the work.