Alkane Hydroxylation by Cytochrome P450: Is Kinetic Isotope Effect a Reliable Probe of Transition State Structure?

Computed kinetic isotope effect (KIE) values for methane hydroxylation by Cytochrome P450, in both high- and low-spin states, compare well with KIE’s for model hydrogen abstraction reactions, thereby demonstrating the utility of KIE as a mechanistic probe and supporting a two-state-rebound mechanism.

[1]  S. Shaik,et al.  A Model “Rebound” Mechanism of Hydroxylation by Cytochrome P450: Stepwise and Effectively Concerted Pathways, and Their Reactivity Patterns , 2000 .

[2]  M. J. Coon,et al.  Cytochrome P450-Catalyzed Hydroxylation of Mechanistic Probes that Distinguish between Radicals and Cations. Evidence for Cationic but Not for Radical Intermediates , 2000 .

[3]  S. Shaik,et al.  Two-state reactivity as a new concept in organometallic chemistry. , 2000, Accounts of chemical research.

[4]  S. Shaik,et al.  Single- and Two-State Reactivity in the Gas-Phase C−H Bond Activation of Norbornane by `Bare' FeO+ , 1999 .

[5]  Jeffrey P. Jones,et al.  Experimental and theoretical study of the effect of active-site constrained substrate motion on the magnitude of the observed intramolecular isotope effect for the P450 101 catalyzed benzylic hydroxylation of isomeric xylenes and 4,4'-dimethylbiphenyl , 1999 .

[6]  M. J. Coon,et al.  Two distinct electrophilic oxidants effects hydroxylation in cytochrome P-450-catalyzed reactions [20] , 1998 .

[7]  Jeffrey P. Jones,et al.  A New Mechanistic Probe for Cytochrome P450: An Application of Isotope Effect Profiles , 1997 .

[8]  J. Dawson,et al.  Heme-Containing Oxygenases. , 1996, Chemical reviews.

[9]  D. Putt,et al.  AN INCREDIBLY FAST APPARENT OXYGEN REBOUND RATE CONSTANT FOR HYDROCARBON HYDROXYLATION BY CYTOCHROME P-450 ENZYMES , 1995 .

[10]  M. Frisch,et al.  Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields , 1994 .

[11]  D. Putt,et al.  Cytochrome P450-catalyzed hydroxylation of hydrocarbons: kinetic deuterium isotope effects for the hydroxylation of an ultrafast radical clock. , 1994, Biochemistry.

[12]  B. Meunier,et al.  Intramolecular kinetic isotope effects in alkane hydroxylations catalyzed by manganese and iron porphyrin complexes , 1993 .

[13]  W. Saunders,et al.  Reaction Rates of Isotopic Molecules , 1987 .

[14]  W. R. Wadt,et al.  Ab initio effective core potentials for molecular calculations. Potentials for K to Au including the outermost core orbitals , 1985 .

[15]  J. Heicklen,et al.  TUNNELLING CORRECTIONS FOR UNSYMMETRICAL ECKART POTENTIAL ENERGY BARRIERS , 1962 .