MOLECULAR RECOGNITION PROPERTIES OF MOLECULAR CONTAINERS IN AQUEOUS SOLUTIONS

Abstract

Supramolecular containers take advantage of non-covalent interactions to do a variety of tasks with high affinity. In particular, water-soluble containers are able to bind biologically relevant molecules to perform useful and interesting tasks. Chapter 1 introduces the field of supramolecular chemistry is introduced and establishes the ability of cucurbit[n]urils (CB[n]) to bind guests with high affinity. It also establishes the uses of water-soluble supramolecular containers, including new-generation pillar[n]arene sulfate (P[n]AS) hosts, in biologically relevant systems. Chapter 2 expands on previous attempts at finding high-affinity host-guest pairings by showing that triamantane amines and triamantane diamines are able to bind CB[8] with femtomolar dissociation constants. It also shows that these ultratight binding complexes can be found in competition measurements with slightly weaker ternary complexes, thus reducing the number of measurements needed and the error of those measurements. Chapter 3 shows the discriminatory power of P6AS towards various amino acids and amino acid amides, as well as their methylated derivatives. This discriminatory power is further explored by showing P6AS shows discriminatory power towards histone 3 peptide sequences that are methylation on either the lysine or arginine. This system was also modeled computationally to investigate the role of water in binding affinity. Chapter 4 expands on the use of P[n]AS in biologically relevant systems by measuring the binding constants and an assay to detect and differentiate various World Anti-Doping Agency (WADA) banned compounds in PBS. The same assay was then used to create a calibration curve in simulated urine for two compounds. In total, the proof-of-concept assay is able to detect Pseudo down to 31.8 μM concentrations.