374 IRON-CONTAINING PROTEINS AND ENZYMES
dichroism (MCD) spectrum is typical of a fi ve - coordinate thiolate - ligated
ferric heme. The question as to why the BME ligand preferentially binds in
the proximal pocket in the enzyme model can be answered by noting distal
pocket steric hindrance provided by amino acid residues his64 and val68.
Large conformational changes would be required to place the BME ligand in
the distal pocket (dioxygen - binding site). In conclusion, one should expect
future research using the Fe III H93G - BME Mb system as a functional model
in mechanistic and catalytic studies of the cytochrome P450 enzyme.
7.4.5.3 Cytochrome P450 Model Compounds: Functional. Ferric – peroxo
species are part of the cytochrome P450 catalytic cycle as discussed previously
in Section 7.4.4. For instance, these ferric – peroxo moieties are known to act
as nucleophiles attacking aldehydic carbon atoms in oxidative deformylations
to produce aromatic species.^60 An example of this work, establishing the
nucleophilic nature of [(porphyrin)Fe III (O 2 )] − complexes, was achieved for
alkene epoxidation reactions by J. S. Valentine and co - workers.^61 The electron -
defi cient compound menadione (see Figure 7.18 ) yielded menadione epoxide
when reacted with a [(porphyrin)Fe III (O 2 )] − complex.
These researchers found that the nucleophilicity of the complex depended
on the electronic nature of the porphyrin. While a [(TPFPP)Fe III (O 2 )] − (TPFPP
equals the dianion ofmeso - tetrakis(pentafl uorophenyl)porphyrin) complex
did not epoxidize alkenes, adding dimethylsulfoxide (DMSO) as an axial
ligand restored the complexes ’ nucleophilicity and ability to epoxidize alkenes.
The authors ascribed this restored capability to push the side - on peroxo into
a more open, end - on, nucleophilic conformation.^62 Watanabe and co - workers
Figure 7.18 Epoxidation of menadione by a [(porphyrin)Fe III (O 2 )] − complex.SOH 3 C CH 3FeIIIO^2 OporphyrinSOH 3 C CH 3FeIIIO2 - OporphyrinOOOOOFeIIIO^2 OporphyrinFeIIIOHporphyrinside-on peroxo end-on peroxo +menadioneDMSO