Various iron porphyrin systems were found to catalyze the dehydration of aldoximes, such as heptanaldoxime or phenylacetaldoxime, into the corresponding nitriles under mild conditions (t = 20 degrees C, neutral or slightly acidic pH). In all these systems, the presence of both the iron porphyrin catalyst and a reducing agent is required, indicating that the active species is the iron(II) porphyrin. The most efficient systems used either an organosoluble iron porphyrin, such as Fe(OEP), in the presence of a carboxylic acid and zinc amalgam as reducing agent, or a water-soluble heme fragment of cytochrome c (microperoxidase MP-11) in the presence of dithionite. The catalytic activity of the systems was greatly increased when using electron-rich iron porphyrins bearing an electron-donating axial ligand, such as imidazole, and a carboxylic acid cocatalyst in close proximity to the iron center. The activity of the best systems was comparable to that of microsomal cytochromes P450 (between 1 and 10 turnovers per min). The intermediate (porphyrin)iron-aldoxime complex formed in those dehydration reactions was isolated in the case of Fe(meso-tetra(2,6-dichlorophenyl)-beta-octachloroporphyrin)[meso-tetra(2,6-dichlorophenyl)-beta-octachloroporphyrin = TDCPCl8P] and characterized by elemental analysis and UV-visible and H-1 NMR spectroscopy. Comparison of the 1H NMR spectra of Fe(TDCPCl8P)(CH3- CHNOH)(2) and Fe(TDCPCl8P)(pyridine)(2) strongly indicates that acetaldoxime is bound to iron(II) via its nitrogen atom in the former. A mechanism for iron porphyrin-catalyzed dehydration of aldoximes based on all these results is proposed. It involves a partial charge transfer from electron-rich Fe(II) to the aldoxime C=NOH moiety, which favors the departure of its OH group assisted by an acid cocatalyst. This illustrates the potential of iron porphyrins as catalysts for new reactions very different from the redox transformations for which they are well-known.