Dynamic Interchanges between Isomers and Charged States of a Polyprotic, Tautomeric Molecule Impact the Growth of Biogenic Urate Crystals

Crystallization of organic or inorganic salts often occur in complex growth environments where the distribution of soluble species near the surfaces of charged crystals differs from that in bulk solution. In this study, we examine the growth of a biogenic organic salt, ammonium urate (NH4HU), over a range of solution pH using a combination of in situ experimental techniques, molecular dynamics simulations, ab initio calculations, and colloidal theory to rationalize the dynamic interchanges between soluble species and their impact on NH4HU crystallization. Urate is a polyprotic acid where each monovalent and divalent ion has two structural isomers (tautomers), leading to a maximum of five different species in the crystallization medium. The diffuse double layer surrounding negatively charged NH4HU crystal surfaces reduces pH in close proximity to the crystal – solvent interface. In accordance with the Poisson–Boltzmann theory, changes in electrostatic potential have a concomitant effect on the concentrations of anionic urate and cationic ammonium ions as a function of distance from the crystal surface. As urate and ammonium ions diffuse from bulk solution, through the diffuse double layer, and incorporate into NH4HU crystal surfaces, the dynamic interchange of speciation and isomerization reactions leads to distinct trends in growth rate as a function of solution alkalinity. We previously reported that the minor monovalent tautomer, which is non-native to the crystal structure, functions as a growth inhibitor. The presence of the minor tautomer leads to unique trends in the response of NH4HU crystal growth rate to changes in supersaturation. This study shows how increasing alkalinity of the growth medium reduces the efficacy of the minor tautomer, resulting in the formation of NH4HU crystals with fewer defects and altering growth versus supersaturation profiles. The collective findings in this study highlight the complexity of crystallization where the solute is both a polyprotic and tautomeric molecule, emphasizing the need to consider multiple aspects of the growth environment through concerted experimental, computational, and theoretical approaches that capture trends in growth rate as a function of solution conditions.