A Uric Acid Polymorph Generated via Thermal Decomposition

Area of Science:

• Crystallography
• Solid-state chemistry
• Materials science

Background:

• Uric acid is a key metabolite of purine metabolism.
• Existing methods yield only one anhydrous uric acid polymorph (Form I).
• Solid-state properties of uric acid polymorphs are not fully understood.

Purpose of the Study:

• To report the discovery and characterization of a novel anhydrous uric acid polymorph.
• To investigate the structural and tautomeric differences between the new form and known forms.
• To explore the formation mechanism of the novel polymorph.

Main Methods:

• Solid-state decomposition of ammonium urate hydrate at elevated temperatures.
• X-ray powder diffraction (XRPD) for structural analysis.
• Rietveld refinement for structure modeling.
• Density Functional Theory (DFT) calculations for tautomer analysis.

Main Results:

• A novel anhydrous uric acid polymorph, UA Form III, was synthesized via solid-state decomposition above 200 °C.
• UA Forms I and III exhibit distinct crystal structures with differences in their b-axes and a/b ratios, detectable by XRPD.
• UA Form III contains a mix of tautomers, unlike UA Form I, which exists exclusively in the triketo form, as indicated by electron density delocalization and DFT calculations.

Conclusions:

• The discovery of UA Form III expands the known polymorphic landscape of uric acid.
• Solid-state transformations offer a route to novel uric acid polymorphs with unique tautomeric compositions.
• Understanding tautomerism in different polymorphic forms is crucial for predicting and controlling uric acid's solid-state behavior.