The equilibrium constants for the coordination of quinine (log K = 2.55 +/- 0.02) and 9-epiquinine (log K = 2.42 +/- 0.05) to form a 1:1 complex with the monomeric ferric hemeoctapeptide from cytochrome c, N-acetylmicroperoxidase-9 have been determined in aqueous solution (pH 6.25, 0.1 M phosphate buffer) at 25 degrees C. The electronic spectra of the complexes suggest that coordination to Fe(III) occurs through the 9-alkoxide group, in agreement with previous NMR work on the interaction of quinine with urohaemin-I [I. Constantinidis and J. D. Satterlee, J. Amer. Chem. Soc. 110, 927 (1988)]. By contrast, two chloroquine molecules bind sequentially to N-acetylmicroperoxidase-8 under the same conditions (log K1 = 3.08 +/- 0.04; log K2 = 1.56 +/- 0.10) in an apparently pi- pi cofacial manner. Molecular mechanics techniques have been applied to a study of the structure of these species with an Fe(III)-porphine nucleus, and show that coordination of the 9-alkoxide group to Fe(III) is possible for both quinine and 9-epiquine, with the quinoline ring system virtually parallel to the porphyrin plane. The energy-minimized structure for the interaction of a single chloroquine molecule with Fe(III)-porphine has the quinoline rings parallel to the periphery of the porphyrin ring.