New Catalytic Properties of Iron Porphyrins: Model Systems for Cytochrome P450-Catalyzed Dehydration of Aldoximes

Abstract

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 °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)-β-octachloroporphyrin) [meso-tetra(2,6-dichlorophenyl)-β-octachloroporphyrin ) TDCPCl 8 P] and characterized by elemental analysis and UV-visible and 1 H NMR spectroscopy. Comparison of the 1 H NMR spectra of Fe(TDCPCl 8 P)(CH 3 -CHNOH) 2 and Fe(TDCPCl 8 P)(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 CdNOH 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.

Discovery of a reaction intermediate of aliphatic aldoxime dehydratase involving heme as an active center

“…The possible mechanism shown in Fig. 5 is largely in accordance with the results of studies on various iron porphyrin systems by Mansuy and coworkers (48,49), suggesting that the ferryl state is formed in the aldoxime dehydration cycle.…”

Modeling heme proteins using atomistic simulations

“…140,141 The consensus rebound mechanism, 148 suggested by Groves et al,151,152,160 corresponds to reactions from species 2 to 4. This involves initial hydrogen abstraction from the alkane (R-H) by the active ferryloxene species (2, Por + Fe IV -O, Por = porphyrin), known also as Compound I, 148,[161][162][163][164][165][166] followed by radical rebound on the ferryl-hydroxo intermediate, 3, to generate the ferric-alcohol complex 4. While the intermediacy of the precursor hydroperoxy complex 1 has recently been ascertained by electron nuclear double resonance (ENDOR) spectroscopy under turnover conditions, 150 compound I (2) remains elusive and the mechanism of hydroxylation is still controversial.…”

Identification of Crucial Histidines Involved in Carbon-Nitrogen Triple Bond Synthesis by Aldoxime Dehydratase

“…However, from results obtained with various iron porphyrin systems and rat liver microsomal cytochromes P450, respectively (31,60), it is suggested that the first step of aldoxime dehydration comprises binding of the aldoxime nitrogen atom to the heme iron, the following step (the ratedetermining step) comprises abstraction of the OH group of aldoxime, which is due to protonation of the OH group by an acidic amino acid residue, and the final step comprises elimination of a hydrogen atom on the carbon neighboring the nitrogen atom of aldoxime.…”