Mutually antagonistic molecular clips: symmetry-breaking non-covalent bonds at the chiral–nonchiral interface

The homochirality of life remains an unresolved scientific question. Prevailing models postulate that homochirality arose through mutual antagonism. In this mechanism, molecules of opposite handedness deactivate each other, amplifying even a small enantiomeric excess into a larger proportion. In this paper, we present chiral molecular clips that replicate this process. Through π-π stacking and complementary hydrogen bonds, shape-persistent clips of opposite chirality bind to each other more strongly than those of the same chirality, resulting in chiral amplification. This process was studied quantitatively, revealing a remarkably high degree (180-fold) of stereoselection, unmatched by any non-covalent assemblies reported to date. We demonstrate how this <i>symmetry-breaking</i>, in conjunction with the <i>chiral composition</i> of the host, impacts the binding of nonchiral molecules. Our findings illustrate how chirality transfer and amplification occur non-covalently from hosts to guests, offering insights into the evolutionary origins of homochirality in life's molecular building blocks.