Doubly chiral pseudopeptidic macrobicyclic molecular cages: Water-assisted dynamic covalent self-assembly and chiral self-sorting

Abstract

Taking advantage of the dynamic covalent chemistry approach, four different cages were synthesized by condensation of tripodal pseudopeptides with 4,4′-biphenyldicarboxyaldehyde. Whereas undesired products of polymeric nature were obtained in polar solvents, the [3+2] cryptand-type macrobicyclic architectures were obtained in excellent yields using chloroform as solvent, even at relatively high concentrations. The presence of two encapsulated water molecules may provide a positive template effect in the low polarity medium. The final macrobicycles display a combination of two types of chirality: d,l chirality due to the asymmetric α-C centers and P,M helical chirality. The homochiral helicity found for all the enantiomerically pure molecular cages indicates strong chirality induction by the asymmetric α-C. Besides, the self-sorting properties of the different chiral pseudopeptides have been studied, resulting in high-fidelity homo-self-sorting. DFT calculations point out that the self-sorting outcome may also be a direct result of the encapsulation of two water molecules within the cavity.