Reference : Structure and formation of synthetic hemozoin: Insights from first-principles calculations

	Document type :	Scientific journals : Article
	Discipline(s) :	Physical, chemical, mathematical & earth Sciences : Chemistry
	To cite this reference:	http://hdl.handle.net/10993/25893

Title :	Structure and formation of synthetic hemozoin: Insights from first-principles calculations
Language :	-
Author, co-author :	Marom, N. [Department of Materials and Interfaces, Weizmann Institute of Science, Rehovoth 76100, Israel, > > > ; Center for Computational Materials, Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX 78712, United States]
	Tkatchenko, Alexandre [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin, Germany]
	Kapishnikov, S. [Department of Materials and Interfaces, Weizmann Institute of Science, Rehovoth 76100, Israel]
	Kronik, L. [Department of Materials and Interfaces, Weizmann Institute of Science, Rehovoth 76100, Israel]
	Leiserowitz, L. [Department of Materials and Interfaces, Weizmann Institute of Science, Rehovoth 76100, Israel]
Publication date :	2011
Journal title :	Crystal Growth and Design
Volume :	11
Issue/season :	8
Pages :	3332-3341
Peer reviewed :	Yes (verified by ORBilu)
Audience :	International
ISSN :	15287483
Keywords :	[en] Antimalarial drug ; Close-in ; Crystallization mechanisms ; First-principles calculation ; Hemozoin ; Infectious disease ; Parasite- ; Pseudopolymorphism ; Van der waals ; XRD ; Calculations ; Crystallization ; Density functional theory ; Molecular crystals ; Porphyrins ; Stereochemistry ; Van der Waals forces ; X ray diffraction ; Dimers
Abstract :	[en] Malaria, an infectious disease once considered eradicated, has reemerged in recent years, primarily due to parasite resistance to commonly used synthetic antimalarial drugs. These drugs act by inhibiting crystallization of the malaria pigment, hemozoin (HZ). Thus, there is a vital need for understanding the process of HZ nucleation. In a companion paper, the pseudopolymorphic behavior of β-hematin, the synthetic form of HZ, has been characterized by X-ray diffraction (XRD) (Straasø, T.; Kapishnikov, S.; Kato, K.; Takata, M.; Als-Nielsen, J.; Leiserowitz, L.Cryst. Growth Des. 2011, 11, DOI: 10.1021/cg200410b). Here, we employ van der Waals (vdW)-corrected density functional theory (DFT) to study the two β-hematin crystal structures and their repeat unit, a heme dimer. We find that vdW interactions play a major role in the binding of the heme dimer and the β-hematin crystal. In addition, accounting for the periodic nature of the system is essential to obtaining the correct geometry of the heme dimer, which is affected by vdW interactions with adjacent dimers in the β-hematin crystal. The different stereoisomers of the heme dimer and their molecular crystals are close in energy, which is consistent with pseudopolymorphism in β-hematin, in agreement with recent XRD experiments. Finally, we use our results to comment on β-hematin crystallization mechanisms. This work demonstrates the viability of vdW-corrected DFT as a tool for gaining valuable insight into pertinent problems involving biological systems. © 2011 American Chemical Society.
Permalink :	http://hdl.handle.net/10993/25893
DOI :	10.1021/cg200409d

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