Abstract
Expanding the Structural Scope of Supramolecular Assemblies and their Applications as Mechanistic Probes
by
Cynthia Marilyn Hong
Doctor of Philosophy in Chemistry
University of California, Berkeley
Professor F. Dean Toste, Co-Chair
Professor Kenneth N. Raymond, Co-Chair
Professor Robert G. Bergman
Chapter 1. A brief background and perspective is provided for the field of supramolecular chemistry. Justification for the continued expansion of the field as well as the work described in this dissertation are presented.
Chapter 2. A new synthetic strategy for the rapid diversification of M4L6 host structures is described. The outlined approach consists of two components: the first is the late-stage functionalization of a ligand precursor to access structural variation while preserving favorable self-assembly properties, and the second is the post-synthetic modification of these functional groups after host assembly. Through this approach, new amine-, azide-, and carboxylatefunctionalized hosts are described with preliminary work and outlook for future applications.
Chapter 3. A novel supramolecular mechanistic probe is introduced, which serves as an experimental platform for isolating and evaluating the role of host charge in supramolecular catalysis. The probe consists of two isostructural metal–ligand catalysts of M4L6 stoichiometry with a significant variation in overall anionic charge: 12- versus 8-. Together, they enable a unique experimental investigation that allows supramolecular structural features to be connected to specific mechanisms of reactivity. Though the importance of charge and electrostatic effects have been highlighted in enzymes and other supramolecular catalysts, this is the first example in which these effects have been experimentally defined in a synthetic microenvironment.
Chapter 4. An unusual enzyme-like mechanism of host–guest binding is described in a new metal–ligand host of Ga4L4 stoichiometry. The introduction of a sufficiently large and tightly bound guest enforces a configurational isomerization in the host from an S4-symmetric conformation to a T-symmetric conformation with a proposed larger internal volume. Detailed mechanistic investigations reveal that this configurationally adaptive binding phenomenon proceeds via a conformational selection mechanism, a unique enzymatic mechanism that has never been definitively recapitulated in a synthetic system prior to this work. This comprehensive study shows that a simple chemical system can stand as a model for analogous behavior in biological systems that are often too challenging to experimentally deconvolute and speaks to the symbiotic relationship between the fields of enzymology and supramolecular chemistry.