Tautomerism is a ubiquitous phenomenon in nature widely presented in many small organics 12 and bio-macromolecules 11 such as peptides, nucleic acids, and proteins. Molecular tautomers are prevalent in many natural and synthetic crystals 13, 14, 15 where they play a central role in the development of pharmaceutical and biological drugs 12 and materials with diverse optical 16, magnetic 17, electrical 18, and chemical 19 properties. Here we examine the intrinsic capability of tautomers 10, 11, 12, or structural isomers, to operate as crystal growth inhibitors. Modifiers of diverse materials 1, 2, 3, 4, 5, 6 exhibit structures and/or compositions that differ from a solute molecule but often contain similar functional motifs that facilitate molecular recognition for modifier binding to crystal surfaces 7, 8, 9. These findings offer potential routes in crystal engineering to strategically control the mechanical or physicochemical properties of tautomeric materials.

The generalizability of this phenomenon is demonstrated for two additional tautomers with relevance to biological systems and pharmaceuticals.

Our study focuses on ammonium urate crystallization and shows that the keto-enol form of urate, which exists as a minor tautomer, is a potent inhibitor that nearly suppresses crystal growth at select solution alkalinity and supersaturation. The macroscopic and microscopic effects imposed by inhibitor-crystal interactions reveal dual mechanisms of inhibition where tautomer occlusion within crystals that leads to natural bending, tunes elastic modulus, and selectively alters the rate of crystal dissolution. Here, we identify tautomers as a new class of modifiers where the dynamic interconversion between solute and its corresponding tautomer(s) produces native crystal growth inhibitors. Modifiers are commonly used in natural, biological, and synthetic crystallization to tailor the growth of diverse materials.

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