Controlling the Stability of Tautomeric Polymorphs in a Multistep Proton-Transfer System Using a Homologue Approach to Fine-Tune the Potential Energy Landscape

The relationship between the temperature-dependent shift in tautomeric equilibrium and the solid–solid phase transition was examined for double-headed Schiff base derivatives (Cns) through a comprehensive analysis combining calorimetry, spectroscopy, and molecular modeling. Varying the length of the aliphatic chains modulated the energy landscape of the Enol and Keto forms in the crystalline state, allowing us to identify three distinct packing types (herringbone, slip-stacked, and wavelike), each exhibiting a characteristic tautomeric preference. These tautomeric polymorphs underwent solid–solid phase transitions from the keto-predominant phase to the enol-predominant phase, where the transitions were driven by a temperature-dependent shift in the tautomeric equilibrium, as observed for negative-to-regular thermochromic switching. Computational studies further elucidated the role of electrostatic interactions intrinsic to each packing type in stabilizing the metastable keto tautomer. These findings provide fundamental insights into the mechanisms governing phase transitions among tautomeric polymorphs, offering a rational framework for designing advanced functional molecular crystals responsive to external stimuli.