title: Sulfur K-edge XAS and DFT calculations on P450 model complexes: effects of hydrogen bonding on electronic structure and redox potentials.
abstract: Hydrogen bonding (H-bonding) is generally thought to play an important role in tuning the electronic structure and reactivity of metal-sulfur sites in proteins. To develop a quantitative understanding of this effect, S K-edge X-ray absorption spectroscopy (XAS) has been employed to directly probe ligand-metal bond covalency, where it has been found that protein active sites are significantly less covalent than their related model complexes. Sulfur K-edge XAS data are reported here on a series of P450 model complexes with increasing H-bonding to the ligated thiolate from its substituent. The XAS spectroscopic results show a dramatic decrease in preedge intensity. DFT calculations reproduce these effects and show that the observed changes are in fact solely due to H-bonding and not from the inductive effect of the substituent on the thiolate. These calculations also indicate that the H-bonding interaction in these systems is mainly dipolar in nature. The -2.5 kcal/mol energy of the H-bonding interaction was small relative to the large change in ligand-metal bond covalency (30%) observed in the data. A bond decomposition analysis of the total energy is developed to correlate the preedge intensity change to the change in Fe-S bonding interaction on H-bonding. This effect is greater for the reduced than the oxidized state, leading to a 260 mV increase in the redox potential. A simple model shows that E degrees should vary approximately linearly with the covalency of the Fe-S bond in the oxidized state, which can be determined directly from S K-edge XAS.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Dey
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Okamura
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ueyama
authors.forename: Britt
authors.initials: B
authors.lastname: Hedman
authors.forename: Keith O
authors.initials: KO
authors.lastname: Hodgson
authors.forename: Edward I
authors.initials: EI
authors.lastname: Solomon
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D007506:Iron-Sulfur Proteins / Q000737:chemistry*; D008433:Mathematics; D008670:Metals / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011487:Protein Conformation; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D013455:Sulfur / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D007506:Iron-Sulfur Proteins; D008670:Metals; D013455:Sulfur; D003577:Cytochrome P-450 Enzyme System