Tautomerism unveils a self-inhibition mechanism of crystallization

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.

An Improved Model for Biogenic Ammonium Urate

“…Figure compares the digitized PXRD pattern of the human urolith from Friedel et al, a second ammonium urate urolith pattern retrieved from the PDF-4 database (PDF 00-021-1518), and the simulated PXRD patterns of triclinic AUH and monoclinic AU . The low angle peak positions at 2θ < 24° in all four patterns are remarkably similar, though differences become more apparent at higher angles.…”

“…They considered the possibility that the material could be a hydrate but concluded it was anhydrous based on multiple analytical tests. More recently, Rimer et al , reported a monoclinic structure for synthetic AU determined from both 3D transmission electron microscopy and Rietveld refinement of PXRD data (refcode: TIGZUI). Structures determined by each method were in excellent agreement with one another and with the Tettenhorst and Gerkin PXRD pattern.…”

Molecular Imposters Functioning as Versatile Growth Modifiers of Urate Crystallization

“…Comparison of NH 4 HU (202̅) surface growth in the absence of modifier (Figure A) and in the presence of MA (Figure B) reveals two effects on layered growth (see Movie S4). These effects occur in addition to those of the minor urate tautomer, which lead to the appearance of corrugated step edges based on a self-inhibition mechanism reported in our previous study . We first measured the relative step velocity v / v o , where v = ν <010> for a fixed concentration of MA and v o is the velocity of the control in the absence of modifier.…”

“…Ammonium urate (NH 4 HU) crystallization was performed in aqueous media using a reported protocol . Crystals of this salt (Figure A) form highly anisotropic morphologies (Figure B) with a C 2/ c space group (Figure C–E) . A view of the basal (202̅) surface (Figure C) shows urate molecules arranged with intermolecular π–π interactions oriented along the b -direction.…”

Probing the Boundary between Classical and Quantum Mechanics by Analyzing the Energy Dependence of Single-Electron Scattering Events at the Nanoscale

“…Experimentally, it has already been demonstrated that the self-coherence length can be used to define electron scattering cross-sections at any energy [ 17 ]. In turn, this allows showing that inelastic phonon scattering dominantly contributes to the omnipresent decay of electron diffraction spots in radiation-soft matter, which is why this approach can be exploited to stimulate time-temperature transformations that hinder/reduce electron-beam-induced object alterations during image acquisitions [ 17 ], and it even allows characterizing extended defects in radiation-sensitive, organic crystals at atomic resolution at room temperature without modifying their crystal structure [ 32 ].…”