Multiple spectroscopic and magnetic techniques show that chloroquine induces formation of the μ-oxo dimer of ferriprotoporphyrin IX.
Interaction of the antimalarial chloroquine (CQ) with ferriprotoporphyrin IX, Fe(III)PPIX, was investigated in aqueous solution (pH7.4) and as a precipitate from aqueous medium at pH5.0. In solution, spectrophotometric titrations indicated strong association (logKobs 13.3±0.2) and a Job plot gave a stoichiometry of 1:2 CQ:Fe(III)PPIX. UV-visible absorbance and magnetic circular dichroism spectra of the complex were compared to various Fe(III)PPIX species. Close similarity to the spectra of the μ-oxo dimer, μ-[Fe(III)PPIX]2O, was revealed. The induction of this species by CQ was confirmed by magnetic susceptibility measurements using the Evans NMR method. The observed low-magnetic moment (2.25±0.02 μB) could only be attributed to antiferromagnetically coupled Fe(III) centers. The value was comparable to that of μ-[Fe(III)PPIX]2O (2.0±0.1 μB). In the solid-state, mass spectrometry confirmed the presence of CQ in the complex. Dissolution of this solid in aqueous solution (pH7.4) resulted in a solution with a UV-visible spectrum consistent with the same 1:2 stoichiometry observed in the Job plot. Magnetic susceptibility measurements made on the solid using an Evans balance produced a magnetic moment (2.3±0.1 μB) consistent with that in solution. Diffusion coefficients of CQ and its complex with Fe(III)PPIX were measured in aqueous solution (3.3±0.3 and 0.6±0.2×10(-10) m(2)·s(-1), respectively). The latter was used in conjunction with an empirical relationship between diffusion coefficient and molar volume to estimate the degree of aggregation. The findings suggest the formation of a 2:4 CQ:Fe(III)PPIX complex in aqueous solution at pH7.4.
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa.
David
D
Kuter
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa.
Stefan J
SJ
Benjamin
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa. Electronic address: timothy.egan@uct.ac.za.
Timothy J
TJ
Egan
D000962:Antimalarials / Q000737:chemistry*; D002738:Chloroquine / Q000737:chemistry*; D004058:Diffusion; D019281:Dimerization; D006427:Hemin / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011524:Protoporphyrins / Q000138:chemical synthesis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D000962:Antimalarials; D011524:Protoporphyrins; C489143:mu-oxo dimeric Fe(III)-protoporphyrin IX; D014867:Water; D006427:Hemin; D002738:Chloroquine
Chloroquine; Ferriprotoporphyrin IX; Heme; MCD; Magnetic circular dichroism