Organic and Inorganic Chemistry

Biography

Biography: Avisikta Upadhyay

Abstract

Biological membranes are primarily self-assembled phospholipid structures, which play crucial role in the survival of living cells by protecting these from the extreme external environments. Although, hydrophobic species such gases, small organic molecules can pass through the lipid membranes, the permeation of hydrophilic entities e.g. inorganic cations, inorganic anions, amino acids, ATP, proteins etc. are prevented completely. Therefore, nature has developed membrane proteins, which allow the selective transport of ions to regulate the cellular pH, osmotic pressure, and also help in the cellular signalling process. The transport of ions across biological membranes is facilitated by molecules that act either as carriers or channels. Channels are usually membrane-bound proteins, while carriers may or may not be membrane-associated. Carriers that shuttle their guests from one side of the membrane to the other side of the membrane need to be lipophilic enough to diffuse through the hydrophobic part of the bilayer. Channels, on the other hand, typically traverse the width of the bilayer membrane and provide a hydrophilic pathway for ions to move across the phospholipid barrier.

Any defect in these channel forming proteins, mainly caused by mutation, results in the imbalance of ion transport process, leading to different types of diseases. For example, cystic fibrosis, Bartter syndrome, Dent’s disease, Myotonia, epilepsy, hyperekplexia, lysosomal storage disease, etc. are diseases, which are caused by the dysfunction of chloride channel forming proteins. There are also evidences that chloride flux has direct correlation to cell death via impairing the intrinsic pathway of apoptosis, without effecting the extrinsic pathway. Considering the role of apoptosis in cancer, there has been tremendous interest in developing synthetic ion transporters which facilitate are capable of selectively transport the Cl^- at low concentration. For example, Prodigiosin and ceramide, naturally occurring anionophores have shown significant anion-transport ability and anticancer activity. The diamide-strapped calix[4]pyrroles, reported by Sessler et al. transport Cl^- and Na⁺ to the intracellular region of cell, and bis-sulfonamide, bis-diol derivatives, reported by our group, transport Cl^- in to the cell via ion carrier and channel forming mechanism. The increase of Cl^- ion concentration in the cell by the transporter molecules leads to reactive oxygen species generation followed by cytochrome-c release from the mitochondria, which subsequently resulted in the apoptosis, so called program cell death.

However, many of the channels forming molecules are too large to be considered as a drug like molecules. Therefore, there has been recent interest in developing small synthetic transporter molecules which are capable of transporting anions across plasma membrane via mobile carrier mechanism. These small molecules can bind with complex anionic guest by employing electrostatic interactions like hydrogen bonding, anion-π interactions, halogen bonds, anion dipole interactions etc.