Self-Assembled Multi-Component Catenanes: The Effect of Multivalency and Cooperativity on Structure and Stability

• Published in: Journal of the American Chemical Society 2012-07, Vol.134 (28), p.11430-11443
• Main Authors: Chung, Mee-Kyung, Lee, Stephen J, Waters, Marcey L, Gagné, Michel R
• Format: Article
• Language: English
• Subjects: Catenanes - chemistry; Chromatography, High Pressure Liquid; Combinatorial Chemistry Techniques; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Molecular Structure; X-Ray Diffraction
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja302347q

Using dynamic combinatorial chemistry, 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 effects of CH−π interactions, inter-ring hydrogen bonds, and β-turn types on [2]-catenane energetics. The non-variant core of the [2]-catenane was shown only to adopt type II′ and type VIII turns at the β-2 and β-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 β-2 and β-4 positions, type II′ and type VIII, respectively, cannot be modified. Mutagenesis studies on the core Aib residue involved in a seemingly key CH−π–CH sandwich reported on how CH−π 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−π interaction also demonstrated that electronegative substituents and the number of CH donors can enhance the effectiveness of a CH−π interaction. These data were interpreted using a cooperative binding model wherein multiple non-covalent interactions create a web of interdependent interactions. In some cases, changes to a component of the web lead to compensating effects in the linked interactions, while in others, the perturbations create a cascade of destabilizing interactions that lead to disproportionate losses in stability.