Acylperoxo

In light of the accepted mechanism for cytochrome P-450 (97-100), a superoxo-Cu(II) intermediate is further reduced, leading to dioxygen activation. Accordingly, a monomeric peroxo or hydroperoxo copper(II) complex serves as a synthetic model for these intermediates of copper-containing monooxygenases. However, no well-characterized complexes of these types are available to date. Formation of a monomeric hydroperoxo or acylperoxo complex was reported to occur when a trans-/u-l,2-peroxo complex, [(Cu(TPA))2(02)]z+, was treated with H+ or RC(O)+, but no details of the structures and properties of the complexes were provided (101). A related complex, a monomeric acylperoxo cop-per(II) complex, was synthesized (102). Low-temperature reaction of a dimeric copper(II) hydroxide complex, [Cu(HB(3,5-iPr2pz)3)]2(OH)2, with 2 equivalents of m-CPBA (3-chloroperoxybenzoic acid) yielded a monomeric acylperoxo complex whose structure was characterized by... 

Turning to the complexes of copper(II), copper(IV) is not stable and heterolysis of the 0—0 bond of the peroxide to form the copper(IV) oxo complex does not occur. In addition, the Lewis acidity of the copper(II) ion is not high enough to enhance the electrophilicity of the coordinated alkyl- or acylperoxide to promote direct oxo-incorporating reactions. With these points in mind, the inert activity of alkyl- and acylperoxo copper(II) complexes, experimentally observed, is understandable, and it is quite unlikely that the mechanism of copper monooxygenase parallels that of cytochrome P-450. 

G. Preparation, Characterization, and Reaction of Acylperoxo-Iron(III) Porphyrin... 

A very similar acylperoxo (or alkylperoxo) intermediate has also been postulated in the peroxidase reactions (48). For example, horseradish peroxidase (HRP) is oxidized by hydrogen peroxide to give Compound I, which has been characterized as an oxo porphyrin ir-cation radical, Fe (=0)Pf [Eq. (7)J (49). The major difference between HRP and P-450 is the fifth ligand, the former having imidazole and the latter a thiol from cysteine. 

However, several questions remain to be answered (1) Is the postulated formation of an acylperoxo-iron(III) complex correct (2) If the answer is yes, how can it be proved (3) Does the peroxo-iron(III) porphyrin complex afford an oxoferryl porphyrin cation radical Recently such an acylperoxo-iron(III) porphyrin complex (16) in solution at low temperature has been directly observed and characterized (78). It was found that 16 did indeed react to yield the oxoferryl porphyrin cation radical 14. 

The effect of acid on the formation of 14 was examined by varying the initial amount of peroxy acid [n in Eq. (10)]. The rate of the formation of 14 (A obs) was found to correlate with [H + ]. Furthermore, for a series of peroxybenzoic acids, the substituent effect for the decomposition of 16 showed a good correlation between obs and Hammett or (p = 0.5) (79). In summary, the reaction of Fe(III)TMP with peroxy acids has been shown to give an oxoferryl porphyrin cation radical, 14, via 0-0 bond cleavage of an acylperoxo-iron(III) precursor,... 

Finally, the sterically hindered porphyrin, hydroxo[tetrakis(triphenyphenyl)-porphyrinatoiron(III)], Fe(III)TTPPP(OH) (19), was prepared and the reaction of 19 with mCPBA yielded the acylperoxo derivative (20), which was stable at low temperature (Scheme VI) (80). An inffared band corresponding to the carbonyl of 20 was observed at 1744 cm - whereas the C=0 bands of free mCPBA and Fe(III)TTPPP(m-chlorobenzoate) appeared at 1735 and 1656 cm", respectively. A very similar IR spectrum (1730 cm" ) has been reported for (PhjP)2Pt00C(0)Ph (81). 

The oxidation of Fe(III)TMP(wi-chlorobenzoate) with 2 equivalents of mCPBA in toluene has been reported by Groves and Watanabe to give iron(III) porphyrin W-oxide (23, (89) Fig. 9). The reaction proceeded quantitatively only at low concentrations of the heme. The presence of an acid such as benzoic acid drastically depressed the formation of 23. The EPR spectrum, H NMR chemical shifts, and solution magnetic moment (5.4 /Zg) indicated that 23 was a high-spin ferric complex. Inspection of the reaction mechanism indicated that the reaction proceeded via the formation of the acylperoxo-iron(III) precursor 16, similar to the reaction carried out in dichloromethane. 

P-450 have also been discussed, especially homolysis and heterolysis of the acylperoxo-iron(lll) complex. In both cases, we consider the active species to be oxoferryl porphyrin cation radicals however, many different reactivities exist between peroxidases and P-450. Ortiz de Montellano et al. have proposed that the position of substrates in the active site might depend on the spatial characteristics of the individual enzymes and influence the detailed course of the reaction (139). These propositions should be carefully examined. Scheme XXV illustrates all of the intermediates that have been observed and/or proposed in the oxygen activation mechanism by P-450 and that have been prepared by the model systems. 

Salcn)IVln "Cl + m-CPBA Catalytic System Characterization of the (Salen)Mn (OOCOAr) Acylperoxo Complex... 

Earlier, Groves and coworkers reported the formation of a manganesc(]II) acylperoxo complex upon interaction of mangancsc(III) porphyrins with pcracids at low temperatures [80,811. Thus, it is natural to suppose that the sharp decrease of the intensity of the EPR signal corresponds to the initial formation of (salcn)Mn (OOCOAr) complex 9. Then, it more slowdy converts into a mononuclear Mn species 10 (Scheme 7). 

Scheme 7. Pi>ssiblc reaction pathways for mangancsc(lll) acylperoxo complex 9...

The rcaciiviiy of complex 9 towards styrene was estimated indirectly to give a second order rale constant l.l 0.4 M min at -70 °C, the main product of the reaction being styrene oxide [50]. On the contrary, 10 reacted with styrene with noticeable rate only at room temperature to yield mainly bcnzaldehyde along with unidentified chain reaction products [50]. Complex 10 was identified as (salcn)Mn 0 complex [50,82,83]. In Ref. 50 special attention was given to the understanding of donor additives (Jacobsen showed that addition of N-meihylmorpholine-.V-oxidc (NMO) resulted in the higher yields and ees of the epoxides). It was found that NMO dramatically increases the reactivity of the acylperoxo complex 9 towards styrene and the rate of oxidation to 10 (similar to push-effect reported for iron(III) porhyrin acylperoxo complexes [84]). 

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