Cooperative Action of Inorganic and Organic Modifiers of Calcium Oxalate Crystallization

Crystallization often occurs in the presence of foreign species ranging from the complex growth media in biological systems to the presence of modifiers or impurities in synthetic processes. Many of these systems contain multiple foreign species, yet relatively few studies examine the cooperative interplay between combinations of crystal growth modifiers for the purpose of tailoring or suppressing crystal formation. Here we examine modifiers of calcium oxalate monohydrate, a key component of kidney stones and a model system for studying pathological crystallization. Organic modifiers designed as therapeutic targets of human diseases frequently operate in solutions with a high ionic strength. In this study, we tested combinations of organic and inorganic ions, focusing on physiologically relevant alkali metals, and showed that the judicious selection of modifier pairs and their relative concentrations leads to unexpected transitions between cooperative modes of antagonism and synergism. These findings reveal effective crystal growth modifier combinations and highlight the active role of the background electrolytes.