Mechanistic insights into C-H bond activation in mononuclear non-heme iron enzymes from a combination of experiment and quantum chemistry

• Applicant: Professor Dr. Frank Neese
• Subject Area: Theoretical Chemistry: Electronic Structure, Dynamics, Simulation
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 49804235

• Final Report Year: 2012

Final Report Abstract

The project is aimed at the elucidation of the catalytic mechanisms of Taurine:α-Ketoglutarate Dioxygenase (TauD), α-KG-dependent oxygenase/halogenase (SyrB2), and Isopenicillin N sythase (IPNS). All of these enzymes feature mononuclear non-heme iron centers, and were investigated in detail experimentally by our american project partners. The combined theoretical and experimental approach enabled us to gain more insight into the relationship between the electronic and geometric structure of these enzymes and their enzymatic activity at the atomic level. The mechanism of oxygen activation and C-H bond activation by TauD has been worked out. The different reactivity for the three viable spin multiplicities originates from the different electronic structures of the rate-limiting transition states. In the reaction the co-substrate αKG functions not only as the electron donor, but also as the electron acceptor. The analysis of the electronic structure changes along the reaction coordinate suggested that intrinsic oxidant for C-H bond activation is a FeIII-oxyl species. The lower reactivity of the triplet ferryl intermediate relative to the quintet counterpart towards C-H bond cleavage can be ascribed to the large Pauli repulsion and the attenuated orbital interaction in the transition state for H-atom abstraction. The TauD-{FeNO}8 species was found to have a triplet ground state and distinctly different reactivity from the isoelectronic TauD-{FeO2}8 species. The geometric and electronic structures of the key intermediates responsible for C-H bond oxidation in SyrB2 and IPNS have been evaluated by comparison of the computed Mössbauer parameters with the experimental determined ones. Our results demonstrated that the two high spin FeIV-oxo intermediates in SyrB2 may have different coordination numbers and hence distinct coordination geometries. In the case of IPNS, the first C-H cleaving intermediate appears to be a quintet end-on FeIII-superoxo complex, whereas the second intermediate is a high spin ferryl species, in close analogy to TauD and SyrB2. A complete list of the calibration constants for a wider range of density functionals and basis sets has been provided. Predication of the correct spin state energetics for transition metal complexes has been tested for various modern density functionals.

Publications

• The Noninnocence of Iron Corroles: A Combined Experimental and Quantum Chemical Study. Chem. Eur. J. 2008, 14, 10839
  Ye, S.; Tuttle, T.; Bill, E.; Gross, Z.; Thiel, W.; Neese, F.
  
• Calibration of Modern DFT-methods for the Prediction of 57Fe Mössbauer Isomer Shifts: Meta-GGA and Double Hybrid Functionals. Inorg. Chem. 2009, 48, 784
  Römelt, M.; Ye, S.; Neese, F.
  
• Multireference Ab initio Studies of Zero Field Splitting and Magnetic Circular Dichroism Spectra of Tetrahedral Co(II) Complexes. Dalton Trans. 2009, 6021
  Sundararajan, M.; Ganyushin, D.; Ye, S.; Neese, F.
  
• Quantum Chemical Study of C-H Activation Reaction. Curr. Opin. Chem. Bio. 2009, 13, 89
  Ye, S.; Neese, F.
  
• Accurate Modeling of Spin State Energetics in Spin-Crossover Systems with Modern Density Functional Theory. Inorg. Chem. 2010, 49, 772
  Ye, S.; Neese, F.
  
• Analysis of Reaction Channels for Alkane Hydroxylation by Nonheme Iron(IV)oxo Complexes. Angew. Chem. Int. Ed., 2010, 49, 5717
  Geng, C-Y.; Ye, S.; Neese, F.
  
• Cryoreduction of the NO-Adduct of Taurine: α-Ketoglutarate Dioxygenase (TauD) Yields an Elusive {FeNO}8 Species. J. Am. Chem. Soc. 2010, 132, 4739
  Ye, S.; Price, J. C.; Barr, E. W.; Green, M. T.; Bollinger, J. M., Jr.; Krebs, C. Neese, F.
  
• Family of V(III)-Tristhiolato Complexes Relevant to Functional Models of Vanadium Nitrogenase: Synthesis and Electronic Structure Investigations by Means of High-Frequency and -Field Electron Paramagnetic Resonance Coupled to Quantum Chemical Computations. Inorg. Chem. 2010, 49, 977
  Ye, S.; Neese, F.; Chu, W-C.; Smirnov, A.; Ozarowski, D.; Tsai, Y-F.; Wang, R-C.; Chen, K-Y.; Liao, J-H.; Hung, C-H.; Telser, J.; Krzystek, J.; Hsu, H-F.
  
• The Unusual Electronic Structure of Dinitrosyl Iron Complexes. J. Am. Chem. Soc. 2010, 132, 3646
  Ye, S.; Neese, F.
  
• Nonheme Iron-oxo Intermediates Form an Oxyl Radical upon Approaching the C-H Bond Activation Transition State. Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 1228
  Ye, S.; Neese, F.
  
• Electronic Structure Analysis of the Oxygen Activation Mechanism by the FeII- and α-Ketoglutarate-Dependent Dioxygenases. Chem. Eur. J. 2012, 18, 6555
  Ye, S.; Riplinger, C.; Hansen, A.; Krebs, C.; Bollinger, J. M., Jr.; Neese, F.