<h3>Title</h3>
<h3>Design and Applications of Binding and Activity-Based Metal Ion Sensors</h3>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p style="text-align: justify;">Metal ions play important roles in biological systems ranging from catalysis to providing structural stability to proteins to regulating electron transfer pathways. Any internal or external factor causing imbalance in metal homoeostasis leads to several disorders. Therefore, it is important to track the localisation and distribution of the metal ions. Among various metal ions, Mn is an essential metal ion, mostly present in +2 oxidation state, which performs vital biological functions. Mn imbalance leads to its accumulation in brain causing manganism, a disease with symptoms similar to Parkinson’s disease. Hence, tracking and imaging Mn ions within living systems can provide insights into Mn regulation. In this context, fluorescent sensors that can detect metal ions would be key chemical tools to image the metal ions including Mn within living cells. Two mechanisms can be utilised to design the fluorescent sensors for metal ions, activity-based sensing (ABS) and binding based sensing (BBS). ABS provides a dual check for the selectivity of metal ions over BBS as it triggers a metal specific transformation upon binding to the metal ion of interest. This allows to overcome the challenges posed by the paramagnetic metal ions and the ones lying low in the Irving Williams Series, specifically Mn. Apart from being essential nutrients, metal ions have also gained important status in the field of metallodrugs. Recently, Mn centred drugs are in use as antioxidants and MRI contrast agents. However, the cellular environment can destabilize the metallodrugs, resulting in reduced efficacy of drugs and cellular toxicity. So, it is also necessary to determine the intracellular stability of the metallodrugs. Here, we aim to develop a library of fluorescent sensors for Mn ions and utilizing a non-invasive fluorescence imaging-based strategy for tracking manganese (Mn) ions and Mn centred metallodrugs in live cells. In the talk, I will discuss: 1. Design and synthesis of a novel activity  based sensor for Mn<sup>2+</sup> ions, the molecule has been characterised and tested for its response towards Mn ions, 2. Synthesis of a known Mn<sup>2+</sup> sensor from our group (M1) to determine the stability constant of the Mn antioxidants, 3. Plan to utilise M1 to detect the accumulation of Mn<sup>2+</sup> in higher organisms, 4. Attempted synthesis of a next generation water soluble sensor for Mn<sup>2+ </sup>ions utilizing a ‘click’ chemistry based modular synthetic scheme.</p>