Spin State of Chloroquine-Heme Complexes: Formation of a Hemin Tetramer Adduct

摘要

Complex formation between the antimalarial drug chloroquine and its presumed target ferriprotoporphyrin IXin three different solutions (pH 6.5, pH 9, and in a water methanol mixture) is characterized by nuclear magneticresonance, UV spectroscopy, and mass spectrometry. NMR paramagnetic relaxation measurements are used to deriveintermolecular distances between the molecules and model structures of the complexes are calculated by moleculardynamics simulations. Observation of an unusual spin state in NMR measurements leads to the postulation of a novel 4:2stoichiometry of the complex, which is supported by mass spectrometry and UV spectroscopy.