Synthesis and characterization of tailor-made additives for inhibition of sparingly soluble calcium salt crystallization

Tailor-made additives were designed and used to modify the nucleation and growth kinetics of calcium oxalate crystallizing from aqueous solution. Tailor-made inhibitors can be used for a variety of purposes that include crystal morphology engineering, kinetic resolution of racemates, reduction of crystal symmetry, assignment of absolute configuration of chiral molecules and polar crystals and control of crystal polymorphism. The molecules of the present study influenced both the morphology and phase transformation of calcium oxalate crystals.; Calcium oxalate, CaC₂O₄, is a sparingly soluble salt widely found in nature. Three hydrate forms of the salt are known including the monohydrate, the dehydrate, and the trihydrate. In the pulp and paper industries, CaC₂O₄ is notorious for forming scale deposits on the equipment. In animals, CaC₂O₄ occurs as a crystal in the urinary tract and constitutes the largest composition in kidney and bladder stones. Clinical management of kidney stones includes taking citric acid supplements which are inhibitors of calcium salt crystallization; however, the amount of citric acid that must be consumed is relatively large (in excess of 2–8 grams per day). Coincidently, large amounts of amino acids (0.8%) are found in kidney stone matrix, and they too have long been considered as crystallization inhibitors; however, several studies have proven otherwise. To improve efficacy of amino acids in this application, we have derivatized several amino acids with cis-expoxysuccinic acid. Subsequently, the crystallization of calcium oxalates in the presence of the derivatized amino acids was studied at ambient temperature. The glycine and the glutamic derivative selectively inhibited the phase transformation and stabilized the dehydrate form of calcium oxalate, while others allowed phase transformation to take place from a metastable calcium oxalate trihydrate, COT, to the thermodynamically stable monohydrate, COM. The lysine derivative inhibited the nucleation and the crystal growth of calcium oxalate much better than citric acid although they both had very little effect on CaC₂O₄ phase transformation. In all cases, the additives modified the crystal shape of the dihydrate form of calcium oxalate.