Self-Assembly and Molecular Recognition Using Squaraine Rotaxanes

Molecular recognition is ubiquitous within nature and controls nearly every aspect of organism structure and function. The ability of biological systems to spontaneously assemble has captured the imaginations of supramolecular chemists and has inspired elegant synthetic mimics that are diverse in both structure and function. The power and versatility offered by molecular recognition and self-assembly is rapidly expanding, and many synthetic receptors have now advanced beyond fundamental studies and are being pursued for practical applications.

This thesis begins with an overview of molecular recognition, the underlying principles that control the phenomenon, and how chemists attempt to design host-guest systems based on this understanding. Of particular importance is the molecular recognition of organic dyes, as the majority of this thesis will focus on the molecular recognition and encapsulation of squaraine dyes to form stable structures known as squaraine rotaxanes (SRs). The thesis will then transition into the development of a new class of chromophores, thiosquaraine rotaxanes, and their evaluation as potential photodynamic therapy agents.

The thesis next introduces SR endoperoxides (SREPs), storable SR analogues that emit light as they cleanly release singlet oxygen. A major drawback to current SREP systems is their very low chemiluminescence yield, and Chapter 3 discusses attempts to increase the light output using various chemical additives. The addition of these additives also led to the discovery and investigation of a new mechanism for light generation in SREPs.

The last two chapters of the thesis focus on the development of a high affinity host-guest system that self-assembles in aqueous media. This system, termed Synthavidin (synthetic avidin) Technology, provides a new paradigm for molecular probe design. Chapter 4 focuses on the discovery of Synthavidin Technology, and the early stage development that led to a highly fluorescent squaraine-macrocycle system that self-assembles in water. Finally, Chapter 5 describes the use of a targeted Synthavidin probe as a bone imaging agent in small animal models. The Synthavidin probes are remarkably stable and demonstrate strong multivalent targeting of skeletal tissue. The thesis concludes with a look toward the future of Synthavidin Technology and its potential use in biomedical and therapeutic applications.