Development of superoxide fluorescent sensors derived from biomimetic metal complexes

Abstract

Superoxide is an important reactive oxygen specie (ROS) in biological systems. It is involved in signaling, immune response and catalysis of many biochemical reactions. Despite of its vital functions, imbalance of superoxide homeostasis can give rise to oxidative stress and cellular damages that could lead to aging or different diseases. Fluorescent probe has emerged as an efficient tool for the imaging of ROS in living cells. In this thesis, the development and evaluation of a metal-based fluorescent turn-on sensor that is selective to superoxide is described. Chapter 1 introduces the background of superoxide in biology and fluorescent probe development. Examples of superoxide probes, metal complex-based fluorescent probes for ROS/RNS and fluorescent probes featuring a C‒O bond oxidative cleavage mechanism are highlighted. Different design strategies for fluorescent probes are also discussed. Chapter 2 describes the design, synthesis and evaluation of a series of complex-fluorophore conjugates as potential selective superoxide probes. One of the Cu(II) complex conjugates, Cu(II)-N4O-Fluo, showed selective fluorescent turn-on in the presence of superoxide. A model Cu(II) complex was synthesized to study the coordination environment of the Cu(II) complex. Chemical modifications on the reporter part of the probe to vary the photophysical properties of the probe is also discussed. Chapter 3 presents experimental details including synthetic procedures, characterization data of the synthesized compounds and procedures for spectroscopic measurements.