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CHANGES OF IRON STATE AND LOCAL IRON ENVIRONMENT OF
MALARIAL PIGMENT'S SUBSTITUTE IN PRESENCE OF
CHLOROQUINE
M.S. Walczak 1*, K. Lawniczak-Jablonska 1, A. Wolska 1, M. Sikora 2,3, A. Sienkiewicz 4, L.
Suárez 5, A. Kosar 5, M.J. Bellemare 5 and D.S. Bohle 5
1Institute of Physics, PAS, Al. Lotników 32/46, 02-668 Warsaw, Poland 2 Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Al. Mickiewicza 30, 3European Synchrotron Radiation Facility, BP 220, 38043 Grenoble, France 4Institute of Physics of Condensed Matter, Ecole Polytechnique Fédérale de Lausanne, Lausanne, CH-1015, 5 Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Canada Keywords: hemozoin, hemozoin's substitute, chloroquine, EXAFS, XANES Malaria remains the world’s most prevalent vector- of Fe atoms in investigated solutions upon chloroquine borne disease, which causes serious health problem drug addition. The main difference revealed by EXAFS particularly in African and Asiatic countries [1]. The concerns the coordination number of the ligand oxygen, most severe form of malaria is caused by Plasmodium which is lower in the presence of chloroquine for both falciparum (Pf) parasite. The intraerythrocytic stage of Pf the water containing solutions. On the other hand the Fe- involves hemoglobin proteolysis and detoxification of O distance is significantly shorter in solution with heme molecules into an inert crystalline material, called smaller H2O/acetic acid ratio and at the presence of drug. malarial pigment, or hemozoin. The crystal structure of Analysis of the XANES revealed small changes in local hemozoin has been solved by X-ray powder diffraction iron geometry and its spin state, being close to S=3/2, in the last years and its synthetic analogue, β-hematin instead of S=5/2 observed in natural product of malaria was synthesized [2]. The ferriprotoporphyrin IX is parasite – micro crystalline hemozoin. believed to be a target for commonly used antimalarial drugs but their interactions are still not understood on molecular level. Figure 2. Comparison of Fourier transformed EXAFS oscillations of solved meso-hematin in chloroquine presence without (MDAAQ) and with (MDAAQ15, Figure 1. Comparison of Fourier transformed EXAFS oscillationsof solved meso-hematin without (MDAA) and with (MDAA15, MDAA30) water addition. Acknowledgements: This work was supported by research
In presented work we are especially interested in drug- grant N20205332/1197 and special project ESRF/73/2006 from induced perturbations of the structures of soluble β- the Ministry of Science and High Education. hematin-like compound, iron(III) (meso-porphyrin-IX anhydride) called meso-hematin. Similarly to its insoluble parent compound, β-hematin, this compound is References
also built of dimers. The XAS measurements on frozen [1] (a) L.H. Miller, D.I. Baruch, K. Marsch, and O.K. Duombo, sample of meso-hematin in solution were performed at "The pathogenic basis of malaria", Nature 415 (2002) 673-
ESRF (station ID26). Pure acetic acid and acetic acid with water of volume ratio respectively 30:1 and 15:1 (b) World Health Organization, The World Malaria Report were used as solvents. The high resolution XANES and 2008, http://apps.who.int/malaria/wmr2008/ EXAFS spectra on iron K-edge enabled us to reveal the [2] S. Pagola, P. W. Stephens, D. S. Bohle, A. D. Kosar, and evolution of iron oxidation state and local environment S. K. Madsen, "The structure of malaria pigment beta-
haematin", Nature 404 (2000) 307-310.

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