The mechanism of beta-hematin formation in acetate solution, parallels between hemozoin formation and biomineralization processes

Formation of beta -hematin in acidic acetate solution has been investigated using quantitative infrared spectroscopy, X-ray diffraction, and scanning and transmission electron microscopy, The process occurs via rapid precipit ation of amorphous (or possibly nanocrystalline) hematin, followed by slow conversion to crystalline beta -hematin. Definitive evidence that the react ion occurs during incubation in acetate medium, rather than during the dryi ng stage, is provided by X-ray diffraction and infrared spectroscopy of the wet material. The reaction follows a sigmoidal function indicative of a pr ocess of nucleation and growth and was modeled using the Avrami equation. R eaction rates and the dimensionality of growth las indicated by the value o f the Avrami constant) are strongly influenced by stirring rate. The reacti on follows Arrhenius behavior, and there is a strong dependence of both the rate constant and the Avrami constant on acetate concentration. Acetate ma y act as a phase transfer catalyst, solubilizing, hematin and facilitating its redeposition as beta -hematin. The pH dependence of the process indicat es that only the monoprotonated species of hematin is active in forming bet a -hematin. The formation of beta -hematin closely parallels many mineraliz ation processes, and this suggests that hemozoin formation may be a unique biomineralization process. Inferences are drawn with respect to the formati on of hemozoin in vivo.