NMR Studies of Chloroquine−Ferriprotoporphyrin IX Complex

By examining natural-abundance 13 C and 15 N solid-state nuclear magnetic resonance (NMR) spectra of acid-precipitated chloroquine−ferriprotoporphyrin IX (CQ−FPIX) 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 13 C spectra demonstrate a loss of signal from aromatic sites, whereas 15 N 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 13 C and 15 N spectra, suggesting the formation of a covalent complex between CQ and FPIX in the solid state.