Intramolecular Hydrogen Bonding-Induced Navigation of Solid Forms through Solution Crystallization

Controlling solid forms via solution-based methods is key to optimizing the stability and performance of molecular materials. In this work, we report a supramolecular model system based on the phenol-isonicotinamide molecular complex (ph-ina), where different halogen atoms systematically installed ortho to the hydroxyl group enabled a characteristic hydrogen bond switching (O–H···N versus O–H···O═C<) in solution and in the resulting cocrystals. A combination of spectroscopy (UV–vis and NMR), theoretical analysis (TD-DFT), and X-ray diffraction (single crystal and powder) was used to characterize the intervening processes from molecular to supramolecular levels. This work uniquely reveals how ortho-halogen substitutions direct molecular self-assemblies in both phases, in solution and solid states, thus offering a modular and scalable approach to the design of functional molecular materials.