The structure and physical analysis of the malaria pigment, hemozoin.

摘要

This dissertation is divided into four sections. Chapter 1 provides background information on the malaria problem and the research that has been conducted thus far. Chapter 2 is devoted to the structure and morphology of hemozoin. In Chapter 3, the chemistry of hemozoin is discussed. Additionally, the effect of hydration on the elemental analysis is presented. Chapter 4 contains simulated docking experiments where various antimalarials, as well as other hemozoin units, were docked to hemozoin.; Malaria pigment, or hemozoin, is a black, insoluble, micro crystalline biomaterial which is formed during the catabolism of hemoglobin by the malaria parasite. The structure of hemozoin (or β-hematin), had eluded researchers for many years, and was finally solved in 2000 using synchrotron X-ray powder diffraction (sXRD). Contrary to all speculation, this elusive structure was found to be a reciprocally bonded dimer comprised of heme units.; The morphology of β-hematin crystallites was resolved using SEM, TEM, and AFM. These crystallites have a regular rectangular prismatic shape, morphologically identical to naturally occurring hemozoin. Furthermore, the unit cell of hemozoin orients perfectly with the surfaces of the crystallite, where the unit cell a, b, and c axes correspond to the (100), (010), and (001) Miller planes, respectively.; The elemental analyses of β-hematin and hemozoin have always been inconsistent with the theoretical values, predominantly low in %C. Using TGA, sXRD, and IR, it was found that a source of this error is hydration. β-Hematin was demonstrated to be reversibly hydrated by alternating moderate heat with exposure to a humid environment.; Using AutoDock3, molecular docking experiments were conducted to investigate the interaction of hemozoin and either itself, or various antimalarials. Docking simulations reproduced, within acceptable error, crystal structure conformations of two hemozoin unit cells. The docking experiments between hemozoin and various antimalarials are discussed in an effort to provide a thermodynamic argument for their interaction.