Supramolecular Host-Guest Interactions, Dynamics and Structure
- Author(s): Mugridge, Jeffrey Scott
- Advisor(s): Raymond, Kenneth N
- et al.
The work described in this thesis examines the noncovalent interactions, dynamics and structure of a self-assembled supramolecular host-guest system. The highly-charged, water soluble supramolecular assembly is able to selectively bind cationic molecules to the host interior and exterior and mediate the physical properties and chemical reactivity of bound guests. Herein, physical organic chemistry in the context of this supramolecular system is used to elucidate some of the fundamental host-guest interactions that underlie guest binding and reactivity.
Chapter 1. First, an overview of different noncovalent interactions and their importance to biological systems is presented. Selected examples of synthetic supramolecular host-guest systems are then reviewed, focusing on examples that illustrate how chemists have used noncovalent interactions to construct complex host architectures and affect guest chemical reactivity. Finally, the [Ga4L6]12- supramolecular assembly, which is the topic of Chapters 2 - 5, is introduced and previous work examining the host-guest chemistry of this system is briefly reviewed.
Chapter 2. Ortho-substituted benzylphosphonium guest molecules are used to quantitatively probe the steric effects of confinement within the [Ga4L6]12- host. Encapsulated guest bond rotational barriers and tumbling rates are measured in different solvents and at elevated external pressures. These studies reveal that despite the flexibility of the host assembly, guest molecules experience significant steric confinement on the host interior and their bond rotational barriers are increased by up to 6 kcal/mol. Significant solvent and pressure effects on the bond rotational rates are also observed; these suggest that the host cavity is smaller or less flexible in organic than in aqueous solution, and that internal solvent pressure is responsible for the observed changes in ligand framework flexibility. The apparently smaller cavity volumes in organic solvents are further supported by NOE distance measurements, which show shorter average host-guest distances in organic, as compared to aqueous, solutions.
Chapter 3. Building on the solvent effects observed in Chapter 2, some additional, qualitative solvent effects are first presented; these show that guest binding and exchange is also sensitive to bulk solvent and that N,N-dimethylformamide can act as weakly bound guest. The second part of this chapter presents a quantitative study of the solvent effects on the thermodynamics and kinetics of guest binding and exchange in the [Ga4L6]12- host. No correlation between the guest binding or exchange parameters across different solvents are observed, illustrating the complexity of host and guest solvation in these highly-charged supramolecular systems.
Chapter 4. A brief literature review of isotope effects on guest binding and exchange in supramolecular host-guest systems is first presented. The measurement of kinetic and equilibrium isotope effects on guest binding and exchange in the [Ga4L6]12- assembly are then described. Protiated guests are found to be more strongly bound to both the host interior and exterior, with significantly larger equilibrium isotope effects observed for C-H/D bonds that can participate in cation-π interactions. DFT-level computations reveal that the equilibrium isotope effects arise from changes in low frequency C-H/D vibrational motions upon guest association. Kinetic isotope effects during the guest ejection process are also observed. A general model to explain both equilibrium and kinetic isotope effects, based only on changes in C-H/D vibrational force constants and zero-point energies is presented. The observation of significant isotope effects on both guest binding and exchange demonstrates the remarkable sensitivity of the [Ga4L6]12- host assembly to even the most subtle changes in guest architecture.
Chapter 5. Guest molecules encapsulated in [Ga4L6]12- experience dramatic changes in their 1H nuclear magnetic resonance (NMR) chemical shifts due to the unique magnetic environment of the host interior. Gauge-independent atomic orbital NMR chemical shift calculations are carried out and compared with experiment to provide information about host-guest conformation and structure.