Synthetic Molecular Approaches for Artificial Anion Transport Systems and their Bio-Applicability

Abstract

Ion transport across cell membrane controls the distribution of collective information stored in the building constituents of cells and performs specific functions e.g. cell proliferation, cellular signaling, regulation of pH and osmotic pressure. Certain classes of membrane proteins, such as channels, carriers, etc., facilitate the ion transport process selectively, overcoming the hydrophobic barrier of the phospholipid bilayer membranes. The dysregulation of ion transport function can lead to various life threatening diseases.

In past few years, the major focus of my research was to develop biomimetic artificial ion transport systems which can confer the information about ion transport across lipid membrane and can be used as a therapeutic agent for the biomedical application. Various design strategies have been incorporated for constructing artificial transport system which allows selective chloride transport across the membrane by forming either ion channel or carrier. We have started with a design of unimolecular artificial ion channel and then moved into the complex supramolecular architectures for ion channel design. Such designs were aimed at the selective chloride transport by controlling the pore diameter, manipulating noncovalent interactions, and incorporating multiple selectivity filters within the channels. The tuneable ion transport activity was achieved by varying the pore diameter of the unimolecular ion channel. A small molecule based supramolecular architecture of ion channel has been introduced which can undergo selective transport of chloride ion by hopping mechanism. We have also developed a new strategy for modulating ion transport activity by controlling the lipophilicity of the transporter molecules. Properties related to ion transport for a particular molecule, transport mechanism and applicability was screened for artificial ion transporting systems. An interesting correlation of chloride binding and lipophilicity with transport activity was derived based on anion carrier system. These molecules further facilitate the delivery of excess chloride ion into cells which may disrupt the ionic homeostasis of the intracellular matrix. The induction of intrinsic pathway of apoptosis because of abnormal ion transport was studied in the case of synthetic ion transport systems. The apoptosis-inducing activity, because of excess chloride transport, could be a potential therapeutic tool for next-generation biomedical applications.