title: Propene activation by the oxo-iron active species of taurine/alpha-ketoglutarate dioxygenase (TauD) enzyme. How does the catalysis compare to heme-enzymes?
abstract: Density functional calculations on the oxygenation reaction of propene by a model for taurine/alpha-ketoglutarate dioxygenase (TauD) enzyme are presented. The oxo-iron active species of TauD is shown to be a powerful and aggressive oxidant, which is able to hydroxylate C-H bonds and epoxidize C=C bonds with low barriers. In the case of propene oxygenation, the hydroxylation and epoxidation mechanisms are competitive on a dominant quintet spin state surface. We have compared the mechanism and thermodynamics of TauD with oxo-iron heme catalysts, such as the cytochromes P450, and found some critical differences. The TauD model is found to be much more reactive toward oxygenation of substrates than oxo-iron complexes in a heme environment with much lower reaction barriers. We have analyzed this and assigned this to the strength of the O-H bond formed after hydrogen abstraction from a substrate, which is at least 10 kcal mol(-)(1) stronger in five-coordinated oxo-iron nonheme complexes than in six-coordinated oxo-iron heme complexes. Since, the metal in TauD enzymes is five-coordinated, whereas in heme-enzymes it is six-coordinated there are some critical differences in the valence molecular orbitals. Thus, in oxo-iron heme catalysts one of the antibonding pi orbitals is replaced by a low-lying nonbonding delta orbital resulting in a lower overall spin state. Moreover, heme-enzymes have an extra oxidation equivalent located on the heme, which is missing in non-heme oxo-iron catalysts. As a result, the oxo-iron species of TauD reacts via single-state reactivity on a dominant quintet spin state surface, whereas oxo-iron heme catalysts react via two-state reactivity on competing doublet and quartet spin states.
authors.affiliation: Manchester Interdisciplinary Biocenter and the School of Chemical Engineering and Analytical Science, The University of Manchester, Sackville Street, P.O. Box 88, Manchester M60 1QD, United Kingdom.
authors.forename: Sam P
authors.initials: SP
authors.lastname: de Visser
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000737:chemistry*; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D000475:Alkenes; D003577:Cytochrome P-450 Enzyme System; C013658:propylene; D007501:Iron; D006899:Mixed Function Oxygenases; C433064:taurine-alpha-ketoglutarate dioxygenase; D010100:Oxygen