Fluorescence detection of biological thiols and axially chiral bodipy derivatives and alternative methodologies for singlet oxygen generation for photodynamic action

Abstract

Calorimetric and luminescent detection of biological thiols namely cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) have attracted great interest due to the their biological significance. There are many reported fluorescent probes for Cys and Hcy, however selective probe designs for GSH remained elusive. We represented in thesis (Chapter 3) a BODIPY based selective fluorescent probe for the in vitro detection of GSH in cancer cell lines. Photodynamic therapy (PDT) is one of the promising and developing treatment modality for certain indications. Therapeutic action is achieved by the generation of cytotoxic singlet oxygen (SO). Most critical compartment of SO production pathway is the sensitizer molecule. In order to get effective inter-system crossing, which is highly needed for singlet oxygen generation, common strategy is to incorporate heavy atoms on sensitizers. However, presence of heavy atoms increases the dark toxicity that is not desired in clinical applications. In Chapter 4, we are introducing a new concept for activatable heavy atom free sensitization of PDT by designing novel orthogonal BODIPY derivatives and detailed computational analysis of this new concept. While dealing with orthogonal BODIPYs, we synthesized for the first time two axially chiral BODIPY derivatives and characterized the enantiopure products, which holds great promise for enantioselective sensing applications (Chapter 5). PDT has two major problems, which are light penetration depth of the incident light and the hypoxia. These two restrictions are addressed in chapter 6, by combining gold nanorods and aromatic endoperoxides.