1:1 Mirror-Symmetric Conformational Pairs and Symmetry Breaking in Achiral Molecules

Abstract

Symmetry is a fundamental principle permeating molecular and crystalline systems, and symmetry breaking remains a core scientific issue for understanding structural evolution, property origins, and functional performance across these two scales. Here, we demonstrate that energy-degenerate mirror-symmetric conformational pairs could provide a molecular-level basis for the observed paired conformations in solid-state flexible achiral molecules, a feature not explicitly considered in conventional structural analysis. Combining density functional theory (DFT) and Cambridge Structural Database (CSD) screening across diverse systems, it is demonstrated that energy-degenerate mirror conformer pairs typically cocrystallize in a 1:1 ratio. This packing characteristic is attributed to nearly equivalent molecular conformational energies and balanced intermolecular interactions. Selective crystallization of a single mirror conformer is rarely observed, and such behavior is enabled by specific molecular–lattice symmetry matching, through which one conformational state is preferentially stabilized relative to its mirror counterpart. This work identifies mirror-symmetric conformational pairs as a critical dual building block, offering new insights into lattice symmetry selection and implications for crystal structure prediction (CSP).