|dc.description.abstract||Zinc is now firmly established as an essential trace element in the human body. Whilst it has many key structural and catalytic fixed roles, it is also found in “mobile” pools in many essential organs and organelles that are readily chelatable. The presence and trafficking of these zinc pools are thought to contribute in some form to many human disease states associated with these organs, for example, Type 2 diabetes in the pancreas, some forms of cancer in the prostate, and even ischemic stroke, epilepsy and Alzheimer’s disease. The exact role however, remains largely unknown and this is due to our current limitations with the methods in which we monitor the movement of this important element in our body. This thesis presents our efforts to develop novel Zn2+ selective chemosensors that can meet contemporary criteria for successful and simple imaging. Many efforts are being made to develop simple fluorescent molecular probes to monitor the trafficking and progress of Zn2+ through these cells and organs in real time via these chelatable “mobile” pools. Chapter 1 will outline some successful efforts towards these and discuss their relevance and mechanisms of action, as well as outlining “click”-chemistry and its’ role in chemosensing to date.
Chapter 2 describes a novel “click”-chemistry approach designed to aid with the simple construction of novel zinc-chelating probes in a facile and high yielding manner. This methodology was taken forward to the synthesis of 6 novel Zn2+ -selective small molecule fluorescent probes that incorporate a cell organelle targeting motif in their structure. These are described in Chapter 3, and their successful testing both in-vitro and in-cellulo in murine pancreatic islet cells is presented and discussed.
Finally, Chapter 4 discusses the development of some modified fluorescent rotaxanes as molecularly interlocked architectures capable of binding and sensing metals, and will specifically focus on how small structural changes led to vast differences in their 4 fluorescence properties, ultimately resulting in a Zn2+ -selective rotaxane in organic media.||en_US