Tautomerism unveils a self-inhibition mechanism of crystallization

Tang, Weiwei and Yang, Taimin and Morales-Rivera, Cristian A. and Geng, Xi and Srirambhatla, Vijay K. and Kang, Xiang and Chauhan, Vraj P. and Hong, Sungil and Tu, Qing and Florence, Alastair J. and Mo, Huaping and Calderon, Hector A. and Kisielowski, Christian and Hernandez, Francisco C. Robles and Zou, Xiaodong and Mpourmpakis, Giannis and Rimer, Jeffrey D. (2023) Tautomerism unveils a self-inhibition mechanism of crystallization. Nature Communications, 14 (1). 561. ISSN 2041-1723 (https://doi.org/10.1038/s41467-023-35924-3)

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Modifiers are commonly used in natural, biological, and synthetic crystallization to tailor the growth of diverse materials. 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. 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. 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 generalizability of this phenomenon is demonstrated for two additional tautomers with relevance to biological systems and pharmaceuticals. These findings offer potential routes in crystal engineering to strategically control the mechanical or physicochemical properties of tautomeric materials.