Microsoft word - r001-wstepniak-biul2009_v4ckj

VIII KSUPS 2009: Abstracts / Synchrotron Radiation in Natural Science Vol. 8, No. 1 - 2 (2009) 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
1 Institute 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, 30-059 Krakow, Poland 3 European Synchrotron Radiation Facility, BP 220, 38043 Grenoble, France 4 Institute of Physics of Condensed Matter, Ecole Polytechnique Fédérale de Lausanne, 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- References
borne disease, which causes serious health problem [1] (a) L.H. Miller, D.I. Baruch, K. Marsch, O.K. Duombo, particularly in African and Asiatic countries [1]. The "The pathogenic basis of malaria", Nature 415 (2002) 673-
most severe form of malaria is caused by Plasmodium 679; (b) World Health Organization, The World Malaria falciparum (Pf) parasite. The intraerythrocytic stage of Pf Report 2008, http://apps.who.int/malaria/wmr2008/ involves hemoglobin proteolysis and detoxification of [2] S. Pagola, P.W. Stephens, D.S. Bohle, A.D. Kosar, S.K. heme molecules into an inert crystalline material, called Madsen, "The structure of malaria pigment beta-haematin", malarial pigment, or hemozoin. The crystal structure of Nature 404 (2000) 307-310.
hemozoin has been solved by X-ray powder diffraction in the last years and its synthetic analogue, β-hematin was synthesized [2]. The ferriprotoporphyrin IX is believed to be a target for commonly used antimalarial drugs but their interactions are still not understood on In presented work we are especially interested in drug-induced perturbations of the structures of soluble β- hematin-like compound, iron(III) (meso-porphyrin-IX anhydride) called meso-hematin. Similarly to its insoluble parent compound, β-hematin, this compound is also built of dimers. The XAS measurements on frozen sample of meso-hematin in solution were performed at ESRF (station ID26). Pure acetic acid and acetic acid Figure 1. Comparison of Fourier transformed EXAFS oscillationsof solved meso-hematin without (MDAA) with water of volume ratio respectively 30:1 and 15:1 and with (MDAA15, MDAA30) water addition. were used as solvents. The high resolution XANES and EXAFS spectra on iron K-edge enabled us to reveal the evolution of iron oxidation state and local environment of Fe atoms in investigated solutions upon chloroquine drug addition. The main difference revealed by EXAFS concerns the coordination number of the ligand oxygen, which is lower in the presence of chloroquine for both the water containing solutions. On the other hand the Fe-O distance is significantly shorter in solution with smaller H2O/acetic acid ratio and at the presence of drug. Analysis of the XANES revealed small changes in local iron geometry and its spin state, being close to S = 3/2, instead of S = 5/2 observed in natural product of malaria Figure 2. Comparison of Fourier transformed EXAFS oscillations of solved meso-hematin in chloroquine Acknowledgements: This work was supported by research
presence without (MDAAQ) and with (MDAAQ15, grant N20205332/1197 and special project ESRF/73/2006 from the Ministry of Science and High Education.

Source: http://www.synchrotron.org.pl/publ/biulet/vo08/p67-Walczak.pdf