Optical properties of complexes of antimalarial drugs with ferriprotoporphyrin IX in aqueous medium. II. The system ferriprotoporphyrin IX-quinidine.

Light absorption and circular dichroism (CD) were recorded at 26 to 27 degrees C in dilute aqueous solutions (10(-4) M) of ferriprotoporphyrin IX (FP) in the presence of (+)-quinidine. In contrast to the appearance of relatively small and positive CD bands between pH 7 and 10, two bands of opposite sign, having unusually large molar ellipticities of the order of 10(6) deg X cm2 X dmol-1 FP were observed in the Soret region near 400 nm at pH 11.0-11.5. This unique complex A was formed only slowly over periods of hours or days at 26 degrees C. By lowering the pH of Complex A below 10, under certain conditions, an "enantiometric" mirror-image CD spectrum, with all bands having opposite sign to Complex A, was obtained in the range of 650 to 300 nm (Complex B), while the light-absorption spectra of Complexes A and B were similar. The formation of Complex A was inhibited at mole fractions of FP greater than 0.5. Also, this complex was not measurably formed at low salt concentrations. Ultracentrifugation measurements of the complex solutions indicated the presence of very high aggregates. Possible interpretations of the optical properties observed are based on interactions between FP molecules, which are assumed to be arrayed chirally within aggregates of FP with quinidine. A comparison between quinine and quinidine complexes of FP is presented.