Uric acid crystallization in humans is associated with undesirable medical conditions including the formation of gout deposits and kidney stones. A major contributing factor to uric acid biomineralization, most often as either monosodium urate (MSU) or anhydrous uric acid (UA), is its relatively low solubility in physiologic solutions. Using bidentate and tridentate binding patterns designed to disrupt the binding motifs observed in the major physiologic forms, several heterocycles were identified which (1) significantly delay the time required for visible uric acid crystals to appear and/or (2) yield new 1:1 uric acid cocrystal phases. All five of the new phases obtained exhibited a multidentate hydrogen bonding motif between components. Fluorescence assays showed that three of the cocrystals were 3–6× more soluble than the natural forms. The same competitive-binding approach was then extended to trimethoprim, an FDA-approved drug with the same substructure as the most effective binding agents. Addition of trimethoprim to uric acid solutions significantly delayed the crystallization times and also yielded a new cocrystal form with a solubility greater than MSU. These results serve to illustrate the potential benefits of repurposing existing pharmaceuticals to treat uric acid diseases.

Here we present an example of an unusual hydrate−anhydrate transformation process induced by defects. Crystallization of uric acid in the presence of substoichiometric concentrations of 2,4-diaminopyrimidine (24-DAP) additives results in uric acid dihydrate (UAD) prisms with trace amounts of 24-DAP included. Prisms maintained in the growth solution transform to anhydrous uric acid (UA) via a highly unusual mechanism in which pairs of thin UA plates emerge from the center of the UAD prism faces which bisect the ± a-axis. With continued growth over several days, the UA pairs eventually fuse together with complete consumption of the initial UAD crystal. A battery of analytical methods are employed in an effort to better understand the complicated role of 24-DAP in the transformation process.

Uricotelic species, such as squamate reptiles, birds and insects, effectively eliminate nitrogen as uric acid in a solid form commonly called urates. Observations made over a decade suggested that the voided urates produced by colubroids (modern snake species) exhibit remarkable differences from those of boids and pythons (ancient snake species). Here, we compare the urates generated by eight captive snake species fed the same diet. Although all fresh urates were wet at the time of excretion, those produced by modern snakes dried to a powdery solid, whereas those of ancient species dried to a rock-hard mass that was tightly adherent to surfaces. Powder X-ray diffraction and infrared spectroscopy analyses performed on voided urates produced by five modern and three ancient snakes confirmed their underlying chemical and structural differences. Urates excreted by ancient snakes were amorphous uric acid, whereas urates from modern snakes consisted primarily of ammonium acid urate, with some uric acid dihydrate. These compositional differences indicate that snakes have more than one mechanism to manage nitrogenous waste. Why different species use different nitrogen-handling pathways is not yet known, but the answer might be related to key differences in metabolism, physiology or, in the case of ancient snakes, the potential use of urates in social communication.

The pathological crystallization of ammonium urate inside the urinary tract is a well-documented medical condition; however, structural studies of the biogenic material have proven challenging owing to its propensity to precipitate as a powder and to exhibit diffraction patterns with widely varying intensities. Using block Rietveld refinement methods of powder diffraction data, here we identify ammonium urate hydrate (AUH) as a likely component in natural uroliths. AUH has a planar 2-D hydrogen-bonded organic framework of urate ions separated by ammonium ions with water molecules residing in bisecting channels. AUH is stable up to 150 °C for short time periods but begins to decompose with prolonged heating times and/or at higher temperatures. Changes in the solid-state structure and composition of synthetic material over a temperature range from 25 to 300 °C are elucidated through thermogravimetric and spectroscopic data, combustion analysis, and time-resolved synchrotron powder X-ray diffraction studies. We contend that biogenic ammonium urate is more accurately modeled as a mixture of AUH and anhydrous ammonium urate, in ratios that can vary depending on the growth environment. The similar but not identical diffraction patterns of these two forms likely account for much of the variability seen in natural ammonium urate samples.