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

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).