Dynamic combinatorial synthesis of donor-acceptor catenanes

Abstract

Dynamic combinatorial chemistry (DCC) is a powerful method for synthesising complex molecules and identifying unexpected receptors. Chapter 1 gives an overview of the concept of DCC and its applications, and discusses its evolution to date. Chapter 2 describes the discovery of a new generation of donor-acceptor [2]catenanes in aqueous dynamic combinatorial systems. The assembly of these [2]catenanes is promoted by a high salt concentration (1 M NaNO3), which raises the ionic strength and encourages hydrophobic association. More importantly, a mechanism that explains and predicts the structures formed is proposed, giving a fundamental insight into the role played by hydrophobic effect and donor-acceptor interactions in this process. Building on these results, Chapter 3 describes the assembly in high salt aqueous libraries of a larger structure: a [3]catenane. Remarkably, the [3]catenane exhibits strong binding interactions with a biologically relevant target – spermine – in water under near-physiological conditions. Its synthesis is improved if the salt is replaced by a sub-mM concentration of spermine, acting as a template. Chapter 4 explores in further detail how subtle variations in the building block design influence the selective formation of either [2] or [3]catenanes. This last section underlines both the advantages and the limitations of the method developed in Chapter 3. After a short conclusion (Chapter 5), Chapter 6 gives experimental details.