Cytochrome mimics

It was also demonstrated that the Rh reduction was highly dependent on the nature of the charge of the surfactant and the reduced rhodium complex catalyzes the reduction of methylviologen, riboflavin, and various manganese(lll) porphyrins. A variety of substrates (pinene, stilbene, styrene, limonene, ethylbenzene) were epoxidized with this P450 cytochrome mimics and with TON in the same order... 

Collman JP, Decreau RA, Yan Y, Yoon J, Solomon El. 2007a. Intramolecular single-turnover reaction in a cytochrome c oxidase model bearing a Tyr244 mimic. J Am Chem Soc 129 5794. 

The PDMS-membrane-occluded FePcY was the first room temperature catalytic membrane and the first solid catalyst dispersed in dense organic polymer.169 The catalytic system mimics the cytochrome P-450 enzyme and can oxidize alkanes at room temperature with rates comparable to those of the... 

Fig. 7 Cytochrome P450-mimic oxidation of fenvalerate (9) by iron(ffl) porphyrin. The values in parentheses are percent of the applied 14C (Asterisk labeled position) after 50 min...

The above sequence mimics the proposed biosynthesis of Ervatamia alkaloids and in this context Thai and Mansuy (190) set out to determine whether an enzyme preparation would be able to promote the same transformation. By incubation of dregamine hydrochloride with a suspension of liver microsomes from a rat pretreated with phenobarbital (as a good inducer of P-450 cytochromes) in the presence of NADPH and 02, 20-epiervatamine (45) was formed together with the major metabolite Nl -demethyldregamine. It is well known that microsomal reaction on tertiary amines results in Af-oxide formation or N-deal-kylation. Thus it is likely that 45 was derived either from a rearrangement of dregamine JV4-oxide, catalyzed by the iron cytochrome P-450 or from one-electron oxidation of 30. 

Figure 6.8 Schematic representation of a cytochrome P450 mimic in which catalytic manganese porphyrins are captured in the bilayer of polymerized vesicles. Colloidal platinum encapsulated in the vesicles in combination with molecular hydrogen serves as a reductant.

Figure 6.9 (a) Components of self-assembled cytochrome P450 mimics, (b) Schematic representation of such a mimic. 

In nature many enzymes are embedded in membranes, which not only serve as a scaffold but also regulate the transport of substrates and products, and control the concentrations of protons and other ions. Instead of embedding molecular catalysts into artificial membranes, as was done for the cytochrome P450 mimic, it is also possible to make amphiphiles that constitute the membranes catalytic themselves. 

The better correlation with in vitro data obtained from hepatocytes (relative to microsomes) deserves further investigation. This difference may be due to a difference in catalytic activity in vivo relative to optimal conditions in vitro. It is possible that use of non-physiological buffer conditions will overstate or understate the contribution of a particular P450 to overall metabolism. For example, the role of cytochrome bs/OR in catalytic activity is influenced by ionic strength (Schenkman et al., 1994 Voznesensky and Schenkman, 1994) which is a variable in microsmal incubations but not in the intracellular space of a hepatocyte. This suggests that performing incubations of cDNA-expressed enzymes under conditions which mimic intact cells may substantially improve correlations. 

This overall sequence of reactions is important because it mimics the natural process of heme rupture during catabolism of waste heme proteins. A blood corpuscle serves, on average, a useful life of about 120 days, and heme systems which perform more dangerous functions, such as cytochrome P450 (which activates molecular oxygen and subsequently hydroxylates hydrocarbons), survive for much shorter periods. In response to an unknown... 

In the present work, the construction of a mimic of cytochrome P-450 is attempted by in situ synthesis of iron-phthallocyanines in the supercages of zeolite Y and in the channels of VPI-5. Its catalytic activity and selectivity is tested in the oxyfunctionalization of n-alkanes with tertiary butyl hydroperoxide. 

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