An efficient mimic of cytochrome P-450 from a zeolite-encaged iron complex in a polymer membrane

Abstract

Many attempts have been made to mimic the catalytic oxidative properties of the enzyme cytochrome P-450. For homogeneous systems the mechanisms of oxidation can be readily determined but proper mimicry of the protein environment is difficult to achieve. Heterogeneous mimics have been designed that use organometallic complexes encapsulated in the supercages of zeolites, which enables control of selectivity and inhibition of auto-oxidation. But these systems do not show any mechanistic analogy with the enzymatic process, and the oxidation rates tend to be low. Here we report a composite catalytic system that achieves realistic mimicry of cytochrome P-450 as well as catalytic turnover rates that make the system industrially viable. Our catalyst incorporates iron phthalocyanine complexes encapsulated in crystals of zeolite Y, which are in turn embedded in a polydimethylsiloxane membrane. The polymer acts as a mimic of the phospholipid membrane in which cytochrome P-450 resides, acting as an interface between two immiscible phases and avoiding the need for solvents or phase-transfer agents. This system oxidizes alkanes at room temperature at rates comparable to those of the enzyme. The observation of a large kinetic isotope effect and the preferential oxidation of tertiary C-H bonds suggest close mechanistic similarities to the enzymatic process.

Detection of P450c17-independent pathways for dehydroepiandrosterone (DHEA) biosynthesis in brain glial tumor cells

“…It is also conceivable that Fe 2ϩ forms complexes with constituents within the C6 cells that are able to mimic the catalytic oxidative behavior of a P450. Previous reports (33,34) suggest that the level of activation of O 2 is similar to that for Fenton reagents and P450 hydroxylases (34), and thus it can affect oxygen insertion at a C17 bond. Therefore, it is not possible now to be certain of the mechanism(s) by which Fe 2ϩ evokes an increase in D production by C6 cells.…”

Aspects of Immobilisation of Catalysts on Polymeric Supports

“…The concept was claimed to be applicable to any catalyst applied in reactions that involve immiscible reagent phases, provided that the appropriate polymer was selected with respect to selective sorption and diffusion of reagents and products. [183] Whereas the formed cyclohexanol and cyclohexanone were found in both the aqueous and the organic phase, [186] products from an n-dodecane oxidation appeared at one membrane side only, thus integrating reaction and full separation in one single process unit. [186] The versatility of the PDMS-occluded membrane systems was further proven with the Ti-containing catalysts TS-1 [187] and Ti-MCM-41.…”

“…[182] Similar types of CMs were tested in a variety of reactions with different kinds of catalysts. [183,184] A zeolite Y with Fe-phthalocyanine (FePc) complexes immobilised in its cages was the first PDMS incorporated catalyst. [185] In the cyclohexane oxidation, the PDMS-membrane formed an optimal solvent phase contacting both immiscible reagent phases.…”

Structural Models for Cytochrome P450�Mediated Catalysis

“…Consequently, it is feasible to utilize such models for the prescreening of novel development compounds that are destined for human exposure. In addition, there are biotechnological possibilities in using the P450 system [38] especially where P450 mimics can be employed as novel catalysts [39]. Ketoconazole is coloured by atom type (carbon -white, hydrogen -pale blue, nitrogen -blue, oxygen -red, chlorine -green), whereas the amino acid residues are coloured by type (amides in magenta; aromatic residues in yellow; hydroxyl sidechains in pale green; hydrophobic residues in pale blue; acidic residues in red; basic residues in blue).…”