Valence tautomerism in synthetic models of cytochrome P450.
CytP450s have a cysteine-bound heme cofactor that, in its as-isolated resting (oxidized) form, can be conclusively described as a ferric thiolate species. Unlike the native enzyme, most synthetic thiolate-bound ferric porphyrins are unstable in air unless the axial thiolate ligand is sterically protected. Spectroscopic investigations on a series of synthetic mimics of cytP450 indicate that a thiolate-bound ferric porphyrin coexists in organic solutions at room temperature (RT) with a thiyl-radical bound ferrous porphyrin, i.e., its valence tautomer. The ferric thiolate state is favored by greater enthalpy and is air stable. The ferrous thiyl state is favored by entropy, populates at RT, and degrades in air. These ground states can be reversibly interchanged at RT by the addition or removal of water to the apolar medium. It is concluded that hydrogen bonding and local electrostatics protect the resting oxidized cytP450 active site from degradation in air by stabilizing the ferric thiolate ground state in contrast to its synthetic analogs.
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India;
Pradip Kumar
PK
Das
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India;
Subhra
S
Samanta
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109.
Ashley B
AB
McQuarters
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109 icad@iacs.res.in lehnertn@umich.edu.
Nicolai
N
Lehnert
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India; icad@iacs.res.in lehnertn@umich.edu.
Abhishek
0000-0002-9166-3349
A
Dey
D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D008958:Models, Molecular; D011166:Porphyrins / Q000737:chemistry*
D011166:Porphyrins; D003577:Cytochrome P-450 Enzyme System
cytochrome P450; entropic contribution; hydrogen bonding; synthetic model; valence tautomerism