Quantifying macrocyclization-induced strain utilizing N-phenylimides as conformational reporters.

Incorporating an N-phenylimide unit into macrocycles enabled measurements of macrocyclization strains by comparing the N-phenylimide's conformational changes to similar units attached to a linear-chain control. Systems of larger macrocycles displayed negligible macrocyclization strain, while smaller macrocycles demonstrated proportionate effects, emphasizing the use of N-phenylimides as conformational reporters of macrocyclization strain.

Solvent Modulation of Aromatic Substituent Effects in Molecular Balances Controlled by CH-π Interactions.

CH-π aromatic interactions are ubiquitous in nature and are capable of regulating important chemical and biochemical processes. Solvation and aromatic substituent effects are known to perturb the CH-π aromatic interactions. However, the nature by which the two factors influence one another is relatively unexplored. Here we demonstrate experimentally that there is a quantitative correlation between substituent effects in CH-π interactions and the hydrogen-bond acceptor constants of the solvating molecule. The CH-π interaction energies were measured by the conformational study of a series of aryl-substituted molecular balances in which the conformational preferences depended on the relative strengths of the methyl and aryl CH-π interactions in the folded and unfolded states, respectively. Due to the favorable methyl-aromatic interactions, the balances were found to exist predominantly in the folded state. The observed substituent effect in the conformational preferences of the balances was controlled by the explicit solvation/desolvation of the aryl proton. The interpretation of the conformational free energy as a function of substituents and solvation using Hunter's solvation model revealed that a linear relationship exists between the sensitivity of aromatic substituent effects (i.e., the ρ values derived from Hammett plots) and the hydrogen-bond acceptor propensity (ßs) of the solvent molecule: ρ = 0.06ßs - 0.04.

Cationic CHπ interactions as a function of solvation.

The energy (ΔG) of a cationic CHπ interaction was measured experimentally through the conformational studies of new molecular torsion balances using proton NMR spectroscopy. Each of the molecular balance adopted folded and unfolded conformations for which the ratio of the conformational equilibrium (i.e., folded/unfolded ratio) provided a quantitative measure of the ΔG as a function of solvation. An excellent linear solvation energy relationship between the ΔG values and the Hunter's solvent hydrogen-bond parameters (αs and ßs) revealed that electrostatic interaction is the physical origin of the observed conformational preferences in solution.