Host-guest chemistry and proton-catalyzed reactivity in a self-assembled supramolecular assembly

The work described in this thesis explores the host-guest chemistry of a self-assembled, water-soluble, supramolecular assembly. The assembly molecule is able to selectively bind substrates and mediate the reactivity of encapsulated guests. The guest-binding properties of the molecular host have been exploited to use the assembly as a catalyst for acid-catalyzed reactions.;Chapter 1. A review of literature examples of stoichiometric and catalytic reactivity mediated by synthetic supramolecular assemblies. The host molecules include functionalized cyclodextrins, hydrogen-bonded assemblies, and metal-ligand architectures. The previous strategies for carrying out chemistry of the M4L6 supramolecular assembly developed by the Raymond group are explored and are used to provide a context in which Chapters 2 through 9 can be viewed.;Chapter 2. The affinity of tetra-alkyl ammonium cations for the exterior of the [Ga4L6]12- assembly is explored using PGSE 1H NMR experiments. Monitoring the diffusion coefficient of the [Ga4L6] 12- assembly as a function of added guest allowed for the observation of ion-association of lipophilic cations to the exterior of the assembly. These studies revealed that the more hydrophobic NPr4+ ion-associates to the exterior of the assembly more strongly than NEt4+;Chapter 3. A crystallographic investigation of host-guest complexes of the M4L6 assembly is described. In the solid state, molecules on the exterior of the assembly are found to interact with different components of the M4L6 assembly through pi-pi, cation-pi, or CH-pi interactions. The volume of the interior cavity of the assembly is modeled using the rolling probe method and found to range from 246--434 A3 depending on the encapsulated guest.;Chapter 4. The preference for encapsulation of monocations in the [Ga4L6]12- assembly is explored in the context of amine encapsulation. Protonation of amines and phosphines allows for encapsulation and shifts the effective basicity of the encapsulated protonated guests. Thermodynamic studies show that upon encapsulation, the amines become more basic with shifts in the effective basicity of up to 4.5 pKa units.;Chapter 5. The chirality of the [Ga4L 6]12- assembly is utilized to reduce the symmetry of encapsulated protonated diamines to allow for the observation of hydrogen bond breaking followed by nitrogen inversion rotation (NIR). The activation barriers for guest exchange are measured to confirm that the NIR process is occurring inside of the assembly. The energetics for the hydrogen bond breaking followed by NIR process are calculated at the G3(MP2)//B3LYP/6-31++G(d,p) level of theory and is found to agree well with the free energies of activation determined inside of the assembly.;Chapter 6. Cyclic amines can be encapsulated in the [Ga4L6]12- assembly upon protonation. The increased hydrogen bonding ability of these amines allows for the formation of proton-bound homodimers and homotrimers inside of the assembly. The generality of homodimer formation is explored with small N-alkyl aziridines, azetidines, pyrrolidines and piperidines. High accuracy G3(MP2) and G3 calculations of the proton-bound homodimers were used to investigate the enthalpy of the hydrogen bond in the proton-bound homodimers and suggests that the enthalpic gain upon formation of the proton-bound homodimers may drive guest encapsulation.;Chapter 7. The thermodynamic stabilization of protonated substrates is exploited to use the [Ga4L6]12- assembly as a catalyst for the acid-catalyzed hydrolysis of orthoformates in basic solution. The kinetics of hydrolysis in the assembly mimic Michaelis-Menten kinetics often observed in enzymes and competitive inhibition is demonstrated. Further mechanistic studies suggest that upon encapsulation, the mechanism of orthoformate hydrolysis shifts from an A-1 mechanism to an A-SE2 mechanism. Comparison of the rates of hydrolysis in the assembly and free in solution revealed rate accelerations of up to 3900 in the case of tri(n-propyl)orthoformate.;Chapter 8. The hydrolysis of orthoformates in the [Ga 4L6]12- assembly is expanded to include the hydrolysis of acetals in basic solution. The kinetics of hydrolysis in the assembly obey Michaelis-Menten kinetics and further mechanistic studies suggest that upon encapsulation, the mechanism of acetal hydrolysis shifts from an A-1 to an A-2 mechanism. Comparison of the rates of acetal hydrolysis in the assembly with the background rate for the reaction reveals rate accelerations of up to 970 over the background reaction.;Chapter 9. The hydrophobic interior cavity of the [Ga 4L6]12- assembly encapsulates tertiary amides. Upon encapsulation, the rotational barrier for C-N bond rotation of the amide is reduced by up to 3.6 kcal/mol in the case of N,N-diethylnicotinamide. Carbon-13 labeling experiments suggest that encapsulation in the assembly may favor a twisted form of the amide.