Serine Octamer Clusters Direct the Chirality of Peptides Formed in Water Microdroplets

The chemistry underlying biological homochirality remains challenging. We propose that non-covalent clusters may have served as the means through which homochiral biochemistry emerged. Serine has long been known to exhibit a chiral preference in clustering to form the octamer; we extend this finding by reporting the effects of a non-zero e.e. in serine on the chiral preference seen in the formation of non-covalent clusters with other amino acids and in the formation of their covalent condensation products, peptides. We show (i) enantiopure serine directs racemic leucine and proline toward enantioselective dipeptide formation in water microdroplets and (ii) likely intermediates are seen as amino acid substitution products into the serine octamer cluster. This work indicates the relevance of microdroplet sprays, such as those found in natural aerosols, to molecular clustering phenomena and to homochirality.