The Development and Application of Rhodamine-Based Fluorescent Sensors

Abstract

Fluorescent sensors are a very promising method for the elucidation of pathologically relevant analytes in complex cellular environments, enabling a deeper understanding of the processes behind health and disease. Rhodamines are highly favorable fluorophores for fluorescent sensors due to their excellent photophysical properties. In this work, several rhodamine-based fluorescent sensors applying sulfur-containing recognition groups have been designed and synthesized. Platinum-based chemotherapeutics have long been successfully used in the clinic for cancer treatment. Fluorescent sensors for platinum drugs and their metabolites are urgently required. Chapter Two describes work towards a rhodamine-based fluorescent sensor, which can selectively respond to Pt(Cl)2(H2O)2, a key metabolite of platinum- based drugs in aqueous environments. While Fenton chemistry has long been known to play a role in inducing cellular stress, the roles that Fenton chemistry plays in pathological processes remain unclear. Chapter Three presents a rhodamine-based fluorescent sensor, RTFt1, which applies both recognition and reactivity strategies to sense the Fenton reactants. The utility of RTFt1 in sensing the Fenton chemistry accompanies ferroptosis and cisplatin-induced cytotoxicity was also demonstrated. Hypochlorous acid is one of the most important ROS, with significant roles in both health and disease. Chapter Four describes investigations of an analogue of RTFt1, RTFt-dimer, that was found to give a selective turn-on response to HOCl. RTFt-dimer was applied to investigations of HOCl in cellular environments, demonstrating that it could be further used to understand HOCl-related biological processes. Considering their versatile application and the diverse sensing strategies by which they can operate, this work confirms that rhodamine-based fluorescent sensors are a powerful tool, and are expected to uncover a greater understanding of biology.