Executive Summary : | Among the various transition metal ions, copper and iron play crucial roles in biological processes. Both these ions are required in optimal concentrations in the body for its normal functioning. For instance, iron has an essential role in red blood cells (RBCs) that generate haemoglobin, store and transport oxygen. Low iron concentration can induce abnormal oxygen delivery, reduce immunity and cause fatigue. Whereas, its high concentration accelerates the reactive oxygen species (ROS) generation, which leads to the flagging of proteins, lipids and nucleic acids. On the other hand, copper is a very essential trace element for human body, but abnormal concentration in its cellular level is linked with neurodegenerative diseases like Wenke's, Wilson's diseases, Alzheimer's, Amyotropic lateral sclerosis, and Prion disease. The optimal concentration of Cu2+ in blood is reported to be 15.7-23.6 mM. Owing to the importance of iron and copper, a strict control over intracellular iron and copper distributions, is very important and therefore monitoring of these ions is imperative for environmental as well as human welfare. In contrast to the conventional techniques, colorimetric and fluorimetric techniques for the detection of metal ions are having advantages in terms of sensitivity, selectivity, fast response time and technical simplicity. Therefore, it is crucial to develop colorimetric and fluorimetric based sensors for the detection of metal ions in trace amount in real environmental samples. In our recent findings, 2,5,7-triarylimidazo[1,2-a] pyridine-8-carbonitrile has been found to display colorimetric and fluorescence "turn-off" response towards Fe2+/Fe3+ and Cu2+ ions. Based on this discovery, it is proposed in this project to design and synthesize next generation cyanoimidazopyridine based molecules for exploring their potential as iron/copper metal ion sensors. In order to discover new cyanoimidazopyridine based scaffolds as colorimetric and fluorimetric metal ion sensors, a lot of efforts are required to be invested which includes the creation of a large library of compounds, performing their photophysical studies, evaluating their applications in live cells (HEK 293T, C6 and K562 cell lines) and theoretical calculations. The computational analysis and structural property relationship will guide us to synthesize molecules with high sensitivity and selectivity towards metal ions. Moreover, the synthesis of next generation molecules seems highly viable, since most of the transformations are well established by the PI's group as well as available in the literature. Pertinent to mention here that two molecules proposed in this project have already been synthesized and preliminary observations on metal binding using UV-Vis spectroscopy are quite encouraging in driving us to submit this project proposal to DST-SERB for generous funding. |