Tautomerism unveils a self-inhibition mechanism of crystallization
Weiwei Tang, Taimin Yang, Cristian A. Morales‐Rivera, Xi Geng, Vijay K. Srirambhatla, Xiang Kang, Vraj P. Chauhan, Sungil Hong, Qing Tu, Alastair J. Florence, Huaping Mo, H.A. Calderón, Christian Kisielowski, Francisco C. Robles Hernández, Xiaodong Zou, Giannis Mpourmpakis, Jeffrey D. Rimer
Abstract
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.