Anion Recognition: From the Perspectives of Fluorescent Probes and Transmembrane Ion Transporters

Abstract

The presence of diverse anions in cells of all the living organisms is a ubiquitous reality and these anions play crucial roles in a number of biological systems, industrial processes as well as in the environment for the maintenance of essential life processes. Recognition of anion is a key event based on several fundamental chemical and biological phenomena such as sensing, catalysis and transport. Among biologically relevant anions, fluoride (F−) ion is one of the most exciting target owing to its well-recognized importance behind miscellaneous health and environmental issues. Albeit several analytical techniques are available to recognize F−, the development of colorimetric fluorescent probes scores a distinct advantage over other methods, because of its direct and prompt detection method and absolutely unambiguous color changes using naked eye. Furthermore, cascade reactions offer a couple of advantages such as atom economy, economy of time and waste generation aspects, all of which were together exploited to design relevant fluorescent probes. Later on, cascade reaction strategy encouraged us to develop off-on probes based on NBD-amine fluorophore for selective detection of F−. The limitation of high response time associated with this probe was overcome by employing another strategy of cascade reaction. Very fast response time and improvement of sensitivity was achieved with this strategy for selective detection of F− using fluorescein as a fluorophore. Further, fluorophore was varied aimed at the improvement of reaction time, sensitivity and aqueous solubility facets. The mechanism of cascade reaction involved in detection of F− was proved by 1H-NMR and HPLC titration and cell-permeability followed by ability to detect intracellular F− was also evaluated for all these probes. In cells, the transport of anions across phospholipid bilayers is an essential phenomenon for maintaining the concentration gradient, imperative for signaling and cellular regulation. Chloride, one of the most important anions, regulates the flux of metabolites into and out of the cell during maintenance of the osmotic pressure, which causes cystic fibrosis, myotonia and epilepsy. Hence, it is important to develop artificial transport systems which can mimic natural ion transport systems to prevent health issues related to imbalance transport of ions. A new class of pre-organized tripodal receptors based on triazine core and bispidine arms were developed to facilitate preorganized cavity formation which was further functionalized to result into controlled anion binding along with facile transport through liposomal membranes. Tripodal tris-amide and tris-urea compounds based on benzoxazine-core were synthesized which led to better Cl− binding ability. Transmembrane anionophoric behavior of the tris-urea receptor along with its theoretical binding model were also demonstrated. To obtain controlled ion transport activity, light gated ion transport activity and chloride selectivity were comprehensively evaluated by designing very small molecules attached with a photo-active alkene core. Also, ion transport activity of cyclo-oligo-(1→6)-β-D-glucosamine based artificial ion transport systems were assessed.