NMR studies of chloroquine-ferriprotoporphyrin IX complex

By examining natural-abundance C-13 and N-15 solid-state nuclear magnetic resonance (NMR) spectra of acid-precipitated chloroquine-ferriprotoporphyrin IX (CQ-FPlX) aggregates, the first direct evidence is provided for CQ-FPIX complexes in the solid state, formed in a physiologic aqueous solution that mimics the environment inside the digestive vacuole of the malaria parasite. The C-13 spectra demonstrate a loss of signal from aromatic sites, whereas N-15 experiments indicate the disappearance of the signal from the N atom of the quinoline ring. These signal losses are due to the paramagnetic Fe(III) center of FPIX. In addition, contact shifts are also observed for both C-13 and N-15 spectra, suggesting the formation of a covalent complex between CQ and FPIX in the solid state.