[Activation of molecular oxygen by hemin complexes]

Area of Science:

• Biochemistry
• Biophysical Chemistry

Background:

• Cytochromes P-450 are crucial enzymes involved in metabolism.
• Understanding their structure and function is vital for drug development and toxicology.
• Existing structural models of P-450 have limitations.

Purpose of the Study:

• To synthesize and characterize functional models of cytochromes P-450.
• To compare the activity of synthesized hemin complexes with native P-450 enzymes.
• To evaluate the potential of these complexes as structural and functional mimics.

Main Methods:

• Synthesis of three hemin complexes with polymethyl methacrylate-based polymers.
• Covalent bonding of hemin via carboxyl or methine groups.
• Coordination bonding of hemin via iron with imidazole-containing polymers.
• Assay of enzyme activity in H2O2-dependent and NADPH-dependent reactions.
• Analysis of electronic and EPR spectra.

Main Results:

• The diimidazole coordination complex exhibited the highest specific activity among synthesized models.
• This complex demonstrated Michaelis-Menten (Vmax) and Michaelis constant (Km) values similar to liver microsomal cytochrome P-450 in H2O2-dependent reactions.
• However, its specific activity in NADPH-dependent reactions was only 1-3% of native cytochrome P-450.
• Spectroscopic data supported its functional but not structural mimicry.

Conclusions:

• The synthesized diimidazole hemin complex serves as a functional model for certain cytochrome P-450 activities.
• It effectively mimics H2O2-dependent reactions, offering insights into P-450 mechanisms.
• It is not a suitable structural model due to significant differences in NADPH-dependent activity.