Executive Summary : | Tracking and monitoring the biological redox homeostasis is crucial as it can significantly influences various cellular functions leading to chronic pathological/physiological conditions. For instances, conditions like oxidative stress or hypoxia are reportedly associated with cardiovascular diseases, diabetes, Alzheimer’s disease, atherosclerosis etc. Noteworthily, controlled release of these prooxidants are necessary for the normal cellular functioning. In this context, the pleomorphic mitochondrion organelle plays a key role in regulating the cellular redox homeostasis and are reported to undergo substantial change in dynamic and morphology in severe clinical conditions. Hence tracking and monitoring the time resolved pro-oxidant level and the mitochondrion adjustments has vital clinical significance. Furthermore, to have an insight into the fundamental mechanistic link between the pro-oxidant level and the clinical conditions, a suitable probe is needed. In this context, a plethora of fluorescent responsive probes for the reactive oxygen and nitrogen species (ROS/RNS) and mitochondrial tags are reported. While, most of these designs are built around cationic core structure and relies on the inner membrane potential for easy cellular permeability/specificity. However, a major drawback of these cationic probes is the poor photochemical stability and induced membrane depolarization leading to change in microenvironment or ruptured cellular membrane. In addition, most of these probes depend on the irreversible reaction between the probe and the analyte for efficient signaling; which may result in increased cytotoxicity. Furthermore, such probes are not efficient to differentiate between the necessary transient release versus the disruptive release of the pro-oxidant which can lead to pathological/physiological conditions. Hence, designing novel redox active neutral probes capable with reversible redox cycle is needed; for monitoring the time resolved changes in the biological redox environment. Note worthily, the design of the probes with reversible mechanistic approach is less common. A key element to the design strategy is to find suitable probe with appropriate reduction potential relevant to biological conditions. Employing a biologically occurring redox responsive moiety, such as flavin, nicotinamide, or glutathione could offer the required redox potential that are tuned to the cellular environment as well as biocompatibility. Among these, flavins are known for their characteristic luminescent nature in different redox states. Given the advantages of the fluorescence imaging techniques over the other associated techniques has prompted us to design novel flavin based neutral and reversible probes for sensing and bioimaging applications. In nutshell, the project aims to deliver novel neutral flavin based probes that allows sensing and monitoring of ROS/RNS and selective bioimaging of cellular redox center-mitochondrion. |