A high‐throughput assay for screening modifiers of calcium oxalate crystallization

Abstract

Controlling crystal habit using growth modifiers provides novel avenues for tailoring properties of crystalline materials. Here, we report on the design of a high‐throughput screening assay for rapid identification of growth modifiers using calcium oxalate monohydrate crystallization as a model system. We conducted a systematic study of assay parameters (sample volume, shaking, and temperature) on crystallization kinetics. Crystallization half‐time (t1/2), defined as the time at which crystallization is 50% complete, was obtained from the logistic fit of kinetic data and used as a measure of growth modifier potency. A test library of 13 peptides composed of aspartic acid and alanine residues was screened to determine their growth promotion or inhibition potentials. Leads identified from this study are in good agreement with ion‐selective electrode measurements and a single time point measurement of free calcium ion concentration is an excellent end‐point for evaluating modifier potency. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3538–3546, 2016

A New Perspective of Gallic Acid on Calcium Oxalate Nucleation

“…Therefore, COM tends to be the main composition of kidney stones. 13,14 A worthy strategy to inhibit stone formation is to target the mechanism of calcium oxalate crystallization or to induce the formation of COT or COD. Previous studies have shown the formation of calcium oxalate clusters prior to nucleation and thus suggest a nonclassical nucleation mechanism.…”

“…However, COM attaches more easily on renal tubular epithelial cells and adheres with macromolecules in urine; thus, it aggregates to stones finally. Therefore, COM tends to be the main composition of kidney stones. , A worthy strategy to inhibit stone formation is to target the mechanism of calcium oxalate crystallization or to induce the formation of COT or COD. Previous studies have shown the formation of calcium oxalate clusters prior to nucleation and thus suggest a nonclassical nucleation mechanism. − Then the amorphous calcium oxalate (ACO), aggregated between clusters, nucleates initially and transforms ultimately to crystals. , In addition to clinical drugs (such as citrate), natural and synthetic modifiers including macromolecules, molecules, and ions have been developed to interfere with the nucleation and/or growth of calcium oxalate .…”

Solubility Measurement and Thermodynamic Correlation of 4-(Hydroxymethyl) Benzoic Acid in Nine Pure Solvents and Two Binary Solvent Mixtures at (283.15–323.15) K

“…4 In the crystallization process, the morphology of the product plays an important role in the performance and physical properties of the target product and its downstream processing units such as filtration, drying, and compaction. 5 p-HMBA usually presents a needle-like crystal, which affects the dissolution rate in vivo. Furthermore, the needle-like crystal shows poor fluidity and it can seriously affect the subsequent blending process and the final tableting process.…”

Molecular Modifiers Suppress Nonclassical Pathways of Zeolite Crystallization

“…To date, this approach has been successfully demonstrated by our group and others for numerous zeolite frameworks, such as MFI (silicalite-1), ,, LTL (zeolite L), ,, CHA (SSZ-13, SAPO-34), , FAU (zeolite Y), MWW (MCM-22), IWR (ECNU-20), AEL (SAPO-11), and MTW (ZSM-12) . Inspiration for this approach derives from natural and biological systems, where organic–inorganic interactions are of paramount importance for the regulation (inhibition or promotion) of crystal growth. − …”