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Doctor of Philosophy (PHD)
Chemistry (Arts and Sciences)
Date of Defense
First Committee Member
Second Committee Member
Third Committee Member
Fourth Committee Member
Thomas K. Harris
This thesis describes the host-guest chemistry between water soluble macrocycles and various series of guests, such as long chain aromatic hydrocarbons, polar small organic molecules, as well as amphiphilic molecules, in aqueous solution. The focus of this thesis is the study of physicochemical properties of the entrapped guest molecules within the macrocycles (hosts) with the help of interdisciplinary use of a variety of methods such as nuclear magnetic resonance, isothermal titration calorimetry and molecular dynamics simulation. To investigate the details of orientation and conformation of encapsulated guest molecule within macrocyclic host capsule (OA capsule), three different sets of aromatic hydrocarbons were selected. In one case, the hydrocarbon chains were fully flexible, and in other two cases rigidity was introduced by incorporating functional group such as alkenyl or alkynyl (Chapter 2). The investigation was carried out with the help of 1H NMR spectroscopy (both 1D and 2D). The conformational features of these guests were complemented with molecular dynamics simulation. It was found that the flexible alkyl chains are capable of adopting some unusual conformations inside the hydrophobic microenvironment of the OA capsule that will be inaccessible to them in solution. Hydrocarbon chains prefer strain free elongated form in gas or solution. Usually, cavity of OA capsule allows the small hydrocarbons to stay in an elongated form. But, the longer hydrocarbon chains, being in a narrow space, are forced to fold or coil. These thermodynamically unstable states are stabilized by specific interactions (C-H/pi and pi-pi) between the guest and the walls of the host OA capsule. Another focus of this thesis was to understand the thermodynamic aspects of host-guest binding between water soluble macrocyclic hosts such as OA, CB7 and various amphiphilic and neutral guest molecules (Chapter 3). Not only that, investigation of the thermodynamic intricacies of the host-guest binding in organic solvent was also our interest. Throughout this study, the effect of different structure of the guests within a given series were explored, either by incorporating different functional groups in a structure, or incorporating similar substituents at different positions within the guest. Depending on the functional group attached to the guest and /or size-shape complimentarity of host-guest pair, the complexation event becomes either both enthalpically and entropically favorable, or enthalpy-entropy compensation was observed. In addition to the binding study of host-guest complexes, we showed with the help of computational techniques that the conformation/orientation play a major role in altering photochemistry of incarcerated guest molecules (Chapter 4). For instance, when cis-4-methyl-1-methylcyclohexyl phenyl ketone was irradiated within OA capsule, it resulted benzaldehyde and 1-methylcyclohexene, a Norrish type I product. A closer look in the MD simulation generated structures of host-guest complexes suggested that the lone pair on oxygen atom of phenylacyl moiety is located far from abstractable gamma hydrogens by rotating through C-C single bond, prohibiting the expected Norrish type II reaction. Similarly, investigation of orientation of adamantanediazirine and its derivatives within OA and CB7, and conformation of 1,4-diaryl-1,3-butadienes within OA capsule with the help of computational techniques helped to answer the outcome of photochemical reactions in confined media. Along with that, the utility of hydrophobic cavity of OA in conducting photodimerization of olefins has been investigated in Chapter 5. Upon UV light irradiation trans-beta-methylstyrene and its derivatives underwent two reactions such as E/Z isomerization and dimerization. Photoisomerization was the major reaction pathway during irradiation in organic solvent. A small amount of head-to-head dimer was identified along with cis isomer. Irradiation of the host-guest complexes of these styrenes with the OA capsule resulted cis isomers as well as dimers. Interestingly, in this case head-to-tail dimers were detected. With the help of 2D NOESY NMR spectra, we speculated that the preorienation of the encapsulated guests in OA capsule led to the head-to-tail dimers.
Host-guest; Molecular Dynamics Simulation; Conformation; Enthalpy-entropy Compensation; NMR Spectroscopy; Binding Constant
Choudhury, Rajib, "Structure and Dynamics of Small Molecules within Water-soluble Hosts: A Thermodynamic, Nuclear Magnetic Resonance Spectroscopic and Computational Study" (2012). Open Access Dissertations. 898.