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

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.