Solvo‐Mechanical Flexing in Cryogenically 2D Flexible Single‐Crystal‐to‐Single‐Crystal Polymorphic Switch

ABSTRACT Stimuli‐responsive molecular crystals that couple mechanical flexibility with structural phase transformations are rare and hold great promise for smart material applications. Here, we report a solvo‐mechanical bending‐induced single‐crystal‐to‐single‐crystal (SCSC) transformation in an indomethacin (IND) polymorph that integrates two‐dimensional (2D) elastic flexibility with polymorphic switching. The 2D elastically bendable methanol solvate crystal of indomethacin (INDM) undergoes a desolvation‐driven transformation into the IND‐δ polymorph upon heating (∼84°C), while retaining both crystallinity and 2D elasticity. In addition, IND‐δ exhibits mechanical flexibility not only at room temperature but also under cryogenic and elevated thermal conditions. In situ time‐resolved atomic force microscopy (AFM) captures the spontaneous transformation of INDM to IND‐δ at room temperature over 10 days, revealing solvent‐directed surface pore formation. Upon further heating, IND‐δ undergoes a SCSC phase transition into the mechanically brittle IND‐γ form, establishing a rare flexible‐to‐flexible‐to‐brittle polymorphic pathway. Mechanical strain analysis and energy framework calculations highlight the role of interlocked hydrogen bonding, π–π stacking, and halogen interactions in enabling directional elasticity. Comparative studies with IND‐α reveal contrasting 1D elastic behavior. Contrary to earlier reports of IND‐δ and IND‐α as plastic and brittle, respectively, this work demonstrates their elasticity and dynamic mechanical characteristics, offering new directions for designing adaptive crystalline materials.