Reference : Structure and formation of synthetic hemozoin: Insights from first-principles calculations
Scientific journals : Article
Physical, chemical, mathematical & earth Sciences : Chemistry
http://hdl.handle.net/10993/25893
Structure and formation of synthetic hemozoin: Insights from first-principles calculations
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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 mailto [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]
2011
Crystal Growth and Design
11
8
3332-3341
Yes (verified by ORBilu)
International
15287483
[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
[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.
http://hdl.handle.net/10993/25893
10.1021/cg200409d

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