Switching “On” and “Off” the Expression of Chirality in Peptide Rotaxanes

The hydrogen-bond-directed synthesis, X-ray crystal structures, and optical properties of the first chiral peptide rotaxanes are reported. Collectively these systems provide the first examples of single molecular species where the expression of chirality in the form of a circular dichroism (CD) response can selectively be switched “on” or “off”, and its magnitude altered, through controlling the interactions between mechanically interlocked submolecular components. The switching is achievable both thermally and through changes in the nature of the environment. Peptido[2]rotaxanes consisting of an intrinsically achiral benzylic amide macrocycle locked onto various chiral dipeptide (Gly-L-Ala, Gly-L-Leu, Gly-L-Met, Gly-L-Phe, and Gly-L-Pro) threads exhibit strong (10−20k deg cm2 dmol-1) negative induced CD (θ) values in nonpolar solvents (e.g. CHCl3), where the intramolecular hydrogen bonding between thread and macrocycle is maximized. In polar solvents (e.g., MeOH), where the intercomponent hydrogen bondin...