Synthetic receptors for ammonium ions using dynamic combinatorial chemistry

The general topic of this dissertation is the development of synthetic receptors for organic ammonium ions in near physiological conditions using disulfide dynamic combinatorial chemistry (DCC). Chapter 1 explains the importance of this development and the associated difficulties when using the conventional, iterative approach: design, synthesis and testing. Then it introduces the external template effects in disulfide DCC that can be used as an alternative, superior approach to conventional chemistry for obtaining synthetic receptors able to work in near physiological medium. Chapter 2 presents a successful use of this approach to develop a synthetic receptor for nicotine. The receptor features an affinity comparable to those of synthetic receptors reported thus far, and is obtained with relatively better yield. Chapter 3 describes the design of a DCL of which nearly all of its macrocyclic, oligomeric members can be amplified, with size selectivity, after being exposed to 30 organic ammonium-ion templates. Chapter 4 shows that the macrocylic oligomers can be amplified, with length-size selectivity, after being exposed to aliphatic α-ω diamines. In chapter 5, a fitting program (DCLFit) was used to reliably estimated the binding affinities of the amplified DCL members to four chosen templates. The binding constants were in close agreement with the ones obtained by ITC, and found to be the highest reported so far for synthetic receptors. Chapter 6 describes the derivatization of the DCL building blocks with natural amino acids to allow the DCL to acquire additional diversity, chiral centers, recognition property, flexibility or rigidity. Valine side chains played a crucial role in the types of the formed products, resulting DCL distributions and DCL responses to templates. Undesirable side reactions were also observed upon introducing the valine residues