A direct synthesis of hexa and pentacoordinate iron porphyrins is described. The bis-β-imidazolylethyl amides of meso- and deuterohemin IX and the corresponding mono (6 or 7) β-imidazolylethyl amides contain two and one imidazoles coordinated to iron(III). They are the prosthetic groups for the active sites of certain cytochrome and globin heme proteins, respectively. The behavior and reactivity of these units in dilute solution were charted by a quantitative comparison of their visible spectra with that of the corresponding iron complexes of mesoporphyrin IX and its dimethyl ester under identical conditions. Their general chemistry is summarized: (i) The porphyrin-attached axial ligands are not easily substituted from iron(III) by solvent or base but they are readily removed from iron by mineral acid. (ii) In contrast, the imidazoles are easily substituted by solvent from iron(II), although they are predominantly bonded to iron in dimethylformamide. (iii) The iron(II) active sites are quickly oxidized by oxygen, and there is no evidence for a stable oxygen complex at room temperature. (iv) Thiomethylethers do weakly coordinate to iron(II) porphyrins, but there is no spectral evidence for their association with iron(III), and there is no discreet absorption at 695 mμ in these solutions. Moreover, the 695 band in native ferricytochrome c can be abolished by the addition of N-acetylmethionine. In contrast, both the stability and spectra of the imidazole and amine adducts are congruent with the properties of cytochrome c. The results emphasize the dominant role of the protein in modulating iron porphyrin reactivity.