title: Interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX, a solid state spectroscopy study.
abstract: To investigate the nature of binding of quinoline antimalarial drugs to heme and to extract experimental evidence for this binding, the interaction of ferriprotoporphyrin IX (FP) with chloroquine and quinacrine (both of which have a similar side chain) and quinoline methanol antimalarials quinine and mefloquine has been studied using IR and NIR-Raman spectroscopy in the solid state. Attenuated total reflectance infrared spectroscopic data clearly show that heme in chloroquine-FP complex is not μ-oxo dimeric indicating that the hypothesis that chloroquine binds to FP μ-oxo dimer with a stoichiometry of 1 chloroquine:2 μ-oxo dimers is not valid in the solid state. Moreover, the first vibrational spectroscopy evidence is presented for the formation of hydrogen bonding between a propionate group of heme and the tertiary amino nitrogen of chloroquine and quinacrine. Raman spectroscopy data does not provide any evidence to support the formation of a similar salt bridge in the complexes of FP with quinine and mefloquine; however, it suggests that the interaction of these drugs with FP happens through coordination of the Fe(III) center of the porphyrin to the 9-hydroxy group of the drug.
authors.affiliation: Department of Chemistry, McGill University, Montreal, Canada.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Asghari-Khiavi
authors.forename: Jitraporn
authors.initials: J
authors.lastname: Vongsvivut
authors.forename: Inna
authors.initials: I
authors.lastname: Perepichka
authors.forename: Adam
authors.initials: A
authors.lastname: Mechler
authors.forename: Bayden R
authors.initials: BR
authors.lastname: Wood
authors.forename: Don
authors.initials: D
authors.lastname: McNaughton
authors.forename: D Scott
authors.initials: DS
authors.lastname: Bohle
mesh_terms: D000962:Antimalarials / Q000737:chemistry*; D001665:Binding Sites; D006427:Hemin / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D011804:Quinolines / Q000737:chemistry*; D013059:Spectrum Analysis, Raman
chemical_list: D000962:Antimalarials; D011804:Quinolines; D006427:Hemin