Self-Assembled Multi-Component Catenanes: The Effect of Multivalency and Cooperativity on Structure and Stability
Abstract
Using dynamic combinatorial chemistry (DCC), mixtures of dipeptide monomers were combined to probe how the structural elements of a family of self-assembled [2]-catenanes affect their equilibrium stability versus competing non-catenated structures. Of particular interest were experiments to target the role of CH-pi interactions, inter-ring hydrogen bonds and Beta-turn types on [2]-catenane energetics. The non-variant core of the [2]-catenane was shown to only adopt type II' and type VIII turns at the Beta-2 and Beta-4 positions, respectively. Monomers were designed to delineate how these factors contribute to [2]-catenane equilibrium speciation/stability. Dipeptide turn adaptation studies, including three-component dynamic self-assembly experiments, suggested that stability losses are localized to the mutated sites, and that the turn types for the core Beta-2 and Beta-4 positions, type II' and type VIII, respectively, cannot be modified. Mutagenesis studies on the core Aib residue involved in a seemingly key CH-pi-CH sandwich reported on how CH-pi interactions and inter-ring hydrogen bonds affect stability. The interacting methyl group of Aib could be replaced with a range of alkyl and aryl substituents with monotonic affects on stability, though polar heteroatoms were disproportionately destabilizing. The importance of a key cross-ring H-bond was also probed by examining an Aib for L-Pro variant. Inductive affects and the effect of CH donor multiplicity on the core proline-pi interaction also demonstrated that electronegative substituents and the number of CH donors can enhance the effectiveness of a CH-pi interaction. These data were interpreted using a cooperative binding model wherein multiple non-covalent interactions create a web of interdependent interactions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 11, 2012
- Accession Number
- ADA595301
Entities
People
- Marcey L. Waters
- Mee-kyung Chung
- Michel R Gagné
- Stephen J. Lee
Organizations
- University of North Carolina at Chapel Hill