Magnetic properties of malarial pigments: towards new antimalarials

The moscito inject the parasite into the blodstream (left panel) which degrades the hemoglobin (middle panel). The parasite detoxifies the liberated Fe species by forming a hemozoin single crystal (right panel). Its magnetic structure is one of the goals of our research.

Malaria continues to be one of the most common human infections, responsible for 1-2 million deaths per year. Today, over 40% of the world’s population, especially in the tropics, is at risk. The most acute form of malaria is caused by a protozoan parasite, Plasmodium falciparum (Pf). Pf degrades hemoglobin in human red blood cells. The liberated heme (Fe-protoporphyrin-IX) is detoxified by Pf into an inert crystalline material, hemozoin.  Many traditional and novel strategies to fight malaria target inhibition of hemozoin growth. Therefore, the knowledge of physicochemical properties of hemozoin is crucial for designing novel anti-malarials.

 

 
HFMF ESR resolves the resonant transitions for FeIII (S=5/2) centers in hemozoin (ß-hematin) and leads to a better understanding of the structure of this malarial pigment.

Hemozoin and its synthetic analogue, b-hematin, are strong paramagnetic systems due to a high content of FeIII (S = 5/2) atoms.  We apply High-field Multi-frequency ESR (HFMF ESR) to study the magnetic properties of the malarial pigments.  In particular, the HFMF ESR approach (magnetic fields up to 16 T, microwave frequencies up to 500 GHz) simplifies otherwise complex ESR spectra observed at conventional low magnetic fields. This approach, together with X-ray absorption near-edge spectroscopy (XANES)[3-5], enabled us to resolve the electronic spin properties of Fe(III) in malarial pigments and gain better insights into their magnetic and structural properties, as seen below [1, 2].

These studies are performed in a close collaboration with the Chemistry Department of McGill University (Montreal) and Institute of Physics of the Polish Academy of Sciences (Warsaw).

 

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References:

[1] A. Sienkiewicz et al., J. Am. Chem. Soc. 128 (14), pp. 4534-4535 (2006) .

[2] M.S. Walczak et al., J. Phys.: Condens. Matter 19 , 285214, pp. 1-11 (2007)

[3] M.S. Walczak, K. Lawniczak-Jablonska, A. Sienkiewicz, M.T. Klepka, L. Suárez, A.J. Kosar, M.J. Bellemare, D.S. Bohle, “XAFS studies of the synthetic substitutes of hemozoin”, Journal of Non-Crystalline Solids  356   (No. 37-40), pp. 1908-1913 (2010).

[4]  M.S. Walczak, K. Lawniczak-Jablonska, A. Wolska, A. Sienkiewicz,  L. Suárez,   A.J. Kosar,  D.S. Bohle, “Understanding Chloroquine Action at the Molecular Level in Antimalarial Therapy: X-ray Absorption Studies in Dimethyl Sulfoxide Solution”,  J. Phys. Chem. B 115, pp. 1145-1150 (2011).

[5] M.S. Walczak, K. Lawniczak-Jablonska, A. Wolska, M. Sikora, A. Sienkiewicz, L. Suárez, A.J. Kosar, M.J. Bellemare, and D.S. Bohle, “Towards Understanding the Chloroquine Action at the Molecular Level in Antimalarial Therapy – X-ray Absorption Studies in Acetic Add Solution”,  J. Phys. Chem. B 115, pp. 4419-4426 (2011).