Crystallization-Driven Template Autocatalysis Induces Mirror Symmetry Breaking and Amplification

Abstract A plausible hypothesis for the origin of biological homochirality invokes chiral symmetry breaking, transfer, and amplification driven by autocatalysis. Here we experimentally demonstrate that crystallization-driven template autocatalysis (CDTA) induces mirror symmetry breaking and chiral amplification in helices. Under solvent-free conditions, CDTA enables the reductive cyclotetramerization of hydrogen-bonded naphthalonitrile precursors into crystalline fibers of naphthalocyanine derivatives. In achiral or racemic systems, a kinetically favored metastable right-handed helical bias emerges during nucleation and develops into P-helical dominant as the fibers elongate, achieving spontaneous mirror symmetry breaking. CDTA also transfers the single handedness of chiral seeds formed from enantiopure analogues to achiral naphthalocyanines through template-assisted replication, resulting in chiral amplification. A key mechanistic step involves the preorganization of naphthalonitrile molecules in a counterclockwise direction at the termini of P-helical fibers via J-type π–π stacking and hydrogen-bonding interactions for autocatalytic transformation. Thus, once mirror symmetry is broken, the resulting chiral perturbation is amplified in a self-replicating manner.