Hemozoin polymer

LDMS is particularly well suited for the analysis of porphyrins.35-39 The heme molecule—a 22 rc-electron conjugated protoporphyrin system (Figure 8.1)—is an efficient photo-absorber in the visible and near UV (with an absorption maximum—the Soret band—near 400nm). This feature, concurrently with its low ionization potential, warrants that direct LDMS will possess extremely low limits for heme detection. The uses of IR or UV LDMS for structural characterization of natural porphyrins and their metabolites, synthetic monomeric porphyrins (e.g., used in photodynamic therapy), porphyrin polymers, and multimeric arrays, have been well documented.41148 In addition fast atom bombardment MS has been used to characterize purified hemozoin, isolated from the spleens and livers of Plasmodium yoelii infected mice.49... 

Fig. (4). The Emerging Structure of Hemozoin. (A) Spectroscopically based model of hemozoin as a linear coordination polymer of heme units linked by a propionate linkage. (B) Hydrogen-bonded model of hemozoin from X-ray powder diffraction data showing two strands of heme units hydrogen bonded via the other propionic acid groups. (C) Current X-ray model of hemozoin revealing a hydrogen-bonded network of heme dimers linked by reciprocating axial propionate linkages.

For over 300 years, the quinoline family of drugs, and chloroquine in particular, has been used as the primary treatment for malaria. Recent studies have demonstrated that this drug inhibits the aggregation of free heme into hemozoin, allowing levels of monomeric heme to rise until cell lysis occurs. Although the determined structure of hemozoin makes the polymer termination scheme proposed by Sullivan et al. unlikely, hemozoin drug heme interactions appear critical in the inhibition mechanism. Thus, researchers have identified the characteristics of... 

Biomimetic processes other than inorganic crystallisation have also been described. Wright and co-workers templated the production of the polymer hemozoin, a crystalline heme aggregate used by malarial parasites in a detoxification process. Understanding and controlling this could lead to new antimalarial drugs. Peptide dendrimers containing multiple repeats of the Ala-His-His sequence known to mediate hemozoin formation were prepared and indeed were shown to induce its production. ... 

Interaction of marine isonitriles derivatives with heme was shown to inhibit the transformation of heme into / -hematin and then hemozoin, a polymer produced by Plasmodium in order to neutralize the toxic (detergent-like) free heme produced in the food vacuole. In addition, isonitriles were shown to prevent both the peroxidative and glutathione-mediated destruction of heme under conditions that mimic the environment within the malaria parasite. In summary, isonitriles, similarly to quinoline antimalarials [38], exert their antiplasmodial activity by preventing heme detoxification. 

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