Toward Identification of the Compound I Reactive intermediate in Cytochrome P450 Chemistry: A QM/MM Study of Its EPA and Mössbauer Parameters.
Quantum mechanical/molecular mechanical (QM/MM) methods have been used in conjunction with density functional theory (DFT) and correlated ab initio methods to predict the electron paramagnetic resonance (EPR) and Mössbauer (MB) properties of Compound I in P450. For calibration purposes, a small Fe(I...
| Published in: | Journal of the American Chemical Society Vol. 127; no. 16; pp. 5840 - 5854 |
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| Main Authors: | , , |
| Format: | Article |
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American Chemical Society
4/27/2005
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=16924247&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 16924247 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 4/27/2005 vid: 127 iid: 16 pid: 997 pub: American Chemical Society artinfo: ui: 16924247 10.1021/ja0424732 ppf: 5840 ppct: 14 formats: tig: atl: Toward Identification of the Compound I Reactive intermediate in Cytochrome P450 Chemistry: A QM/MM Study of Its EPA and Mössbauer Parameters. aug: au: Schöneboom, Jan C. Neese, Frank Thiel, Walter affil: Max-Planck-Institut für Kohlenforschung, Kaiser- Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany Max-Planck-Institut für Bioanorganische Chemie, Stiftstrasse 34-36, D-45413 Mülheim an der Ruhr, Germany su: Density functionals Electron paramagnetic resonance Functional analysis Magnetic resonance Atoms Chemistry sug: subj: Density functionals Electron paramagnetic resonance Functional analysis Magnetic resonance Atoms Chemistry ab: Quantum mechanical/molecular mechanical (QM/MM) methods have been used in conjunction with density functional theory (DFT) and correlated ab initio methods to predict the electron paramagnetic resonance (EPR) and Mössbauer (MB) properties of Compound I in P450. For calibration purposes, a small Fe(IV)-oxo complex [Fe(O)(NH)(HO)] was studied. The A and A states (in C, symmetry) are found to be within 0.1-0.2 eV. The large zero-field splitting (ZFS) of the (FeO) unit in the A state arises from spin-orbit coupling with the low-lying quintet and singlet states. The intrinsic g-anisotropy is very small. The spectroscopic properties of the model complex [Fe(O)(TMC)(CHCN)] (TMC = 1,4,8,- 11 -tetramethyl-1 ,4,8,11 -tetraazacyclotetradecane) are well reproduced by theory. In the model complexes [Fe(O)(TMP)(X)] (TMP = tetramesitylporphyrin, X = nothing or HO) the computations again account for the observed spectroscopic properties and predict that the coupling of the A state of the (FeO) unit to the porphyrin radical leads to a low-lying sextet/quartet manifold ∼12 kcal/mol above the quartet ground state. The calculations on cytochrome P450, with and without the simulation of the protein environment by point charges, predict a small antiferromagnetic coupling (J ≈ -13 to -16 cm; Ĥ = - 2JSS) and a large ZFS > 15 cm (with E/D ≈ 1/3) which will compete with the exchange coupling. This leads to three Kramers doublets of mixed multiplicity which are all populated at room temperature and may therefore contribute to the observed reactivity. The MB and ligand hyperline couplings (N, H) are fairly sensitive to the protein environment which controls the spin density distribution between the porphyrin ring and the axial cysteinate ligand. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2005 holdings: @attributes: islocal: N |
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