A New Perspective of Gallic Acid on Calcium Oxalate Nucleation

The therapeutics for nephrolithiasis have created an awareness of the potential effects of crystal modifiers on the biocrystallization process. The crystallization of calcium oxalate, a primary constituent of kidney stones, is confirmed to be inhibited by natural or synthetic modifiers, but the induction of calcium oxalate dihydrate and trihydrate, which is likewise effective for retardation of stone formation, is rarely focused on. Herein, we performed a systematic investigation of the effect of gallic acid, a natural polyphenol, on the nucleation of calcium oxalate from both experimental and simulation approaches. Our results reveal that the solution species of gallic acid alter the nucleation pathways of calcium oxalate and induce the formation of different types of amorphous structures corresponding to calcium oxalate hydrates. Different species of gallic acid regulate the formation of three types of amorphous calcium oxalates (ACOs) by incorporating the proper water contents and specific interactions. Fluorescence microscopy further demonstrates clearly the incorporation of gallic acid in the nucleated calcium oxalate precipitates. These findings unveil the nucleation mechanism of different calcium oxalate hydrates with the inclusion of modifiers and provide insights for an understanding of stone formation and its potential inhibitors.