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 amplification in helices. CDTA enables the reductive cyclotetramerization of hydrogen-bonded naphthalonitrile precursors into crystalline fibers of naphthalocyanine derivatives. In achiral or racemic systems, a kinetically controlled right-handed helical bias emerges during secondary nucleation and develops into P-helical dominance as the fibers elongate, achieving mirror symmetry breaking. CDTA also transfers the single handedness of chiral seeds formed from enantiopure analogs 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 imbalance is amplified in a self-replicating manner.