title: Toward understanding the chloroquine action at the molecular level in antimalarial therapy--X-ray absorption studies in acetic acid solution.
abstract: The local atomic structure around the central iron of the synthetic soluble analog of malarial pigment in acetic acid solution and with addition of chloroquine as found by X-ray absorption spectroscopy is reported. The special interest was drawn to the axial linkage between the central iron atom of the ferriprotoporphyrin IX (FePPIX) coordinated axially to the propionate group of the adjacent FePPIX. This kind of bonding is typical for hematin anhydride. Detailed analysis revealed differences in oxygen coordination sphere (part of dimer linkage bond) between synthetic equivalent of hemozoin in the powder state and dissolved in acetic acid and water at different concentrations mimicking the physiological condition of the parasite's food vacuole. The results of performed studies suggest that the molecular structure of synthetic analogue of hemozoin is no longer dimer-like in acidic solution. Further changes in atomic order around Fe are seen after addition of the antimalarial drug chloroquine.
authors: Institute of Physics, Polish Academy of Sciences, Warsaw, Poland. mwalczak@ifpan.edu.pl
authors: Monika S
authors: MS
authors: Walczak
authors: Krystyna
authors: K
authors: Lawniczak-Jablonska
authors: Anna
authors: A
authors: Wolska
authors: Marcin
authors: M
authors: Sikora
authors: Andrzej
authors: A
authors: Sienkiewicz
authors: Liliana
authors: L
authors: Suárez
authors: Aaron J
authors: AJ
authors: Kosar
authors: Marie-Josee
authors: MJ
authors: Bellemare
authors: D Scott
authors: DS
authors: Bohle
mesh_terms: D019342:Acetic Acid / Q000737:chemistry; D000962:Antimalarials / Q000737:chemistry*; D002738:Chloroquine / Q000737:chemistry*; D006420:Hemeproteins / Q000737:chemistry*; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D008958:Models, Molecular; D056928:X-Ray Absorption Spectroscopy
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; C020753:hemozoin; D002738:Chloroquine; D019342:Acetic Acid