쿠커비[7]투릴을 이용한 수용액상의 선택적 분자 인지 연구

Abstract

This thesis describes the host-guest chemistry between water soluble macrocycles and various types of guests, such as saccharides and drug molecules in aqueous solution. The study focus on the physicochemical properties of the encapsulated guest molecules within the macrocycles (hosts) with a help of a variety of methods such as nuclear magnetic resonance spectroscopy (NMR), isothermal titration calorimetry (ITC) and crystallography as well as theoretical calculations. Chapter 1 is a brief overview of the recent developments in molecular recognition and host-guest chemistry. Firstly, a general concept of molecular encapsulation and various examples of macrocyclic receptors are given. This is followed by the introductory aspects of cucurbit[n]uril (CB[n]) molecular containers, their supramolecular chemistry and applications including detection of biological molecules. Chapter 2 describes the unusual conformations of hydrophilic guests, amino saccharides (D-glucosamine hydrochloride, D-galactosamine hydrochloride, D-mannosamine hydrochloride and 6-amino-6-deoxy-D-glucose) bound to the molecular host, cucurbit[7]uril (CB[7]). The thermodynamics of CB[7]-amino saccharides complexation is extensively examined by ITC and several 1D and 2D NMR studies clarified the structural information. CB[7] shows excellent selectivity and high affinity (Ka = 10^3 to 10^4 M-1) towards cationic amino saccharides in water compared to any existing synthetic receptors. Interestingly, CB[7] confines the saccharides in its hydrophobic cavity and stabilizes the α-anomer against mutarotation, by isolating it from water. Chapter 3 presents the X-ray crystallographic and computational studies (density functional theory (DFT) calculations and molecular dynamic (MD) simulations) on the supramolecular stabilization of amino saccharides inside CB[7] cavity. By adopting both experimental and computational means, the host-guest interactions involving the weakly binding amino saccharides are characterized. Through solid state crystallographic analysis, we confirm that α-anomers are buried inside the CB[7] cavity, and also the calculated gas phase structures agree well with these observations. We further calculate the binding free energies of the complexes and demonstrate the preference of αover β anomer in solution. The MD simulations identify the effect of aqueous environment on complexation, anomeric selection and stabilization of hydrophilic guests. Chapter 4 demonstrates the sensitive and selective water-stable drug sensing system based on the complex between CB[7] and amphetamine-type stimulants (ATS). The complexation thermodynamics of CB[7] with a group of drugs (amphetamine, methamphetamine and MDMA) and their analogues in pure water is extensively examined by ITC. The binding affinity for amphetamine is measured to be 1.2 × 10^6 M-1, which is strong enough for developing sensing device based on molecular recognition. In addition, the conformational and structural information of the complexes between CB[7] and ATS is derived from 1H-NMR and X-ray crystallographic studies.