title: Combined experimental and theoretical study on the reactivity of compounds I and II in horseradish peroxidase biomimetics.
abstract: For the exploration of the intrinsic reactivity of two key active species in the catalytic cycle of horseradish peroxidase (HRP), Compound I (HRP-I) and Compound II (HRP-II), we generated in situ [Fe(IV) O(TMP(+.) )(2-MeIm)](+) and [Fe(IV) O(TMP)(2-MeIm)](0) (TMP=5,10,15,20-tetramesitylporphyrin; 2-MeIm=2-methylimidazole) as biomimetics for HRP-I and HRP-II, respectively. Their catalytic activities in epoxidation, hydrogen abstraction, and heteroatom oxidation reactions were studied in acetonitrile at -15 °C by utilizing rapid-scan UV/Vis spectroscopy. Comparison of the second-order rate constants measured for the direct reactions of the HRP-I and HRP-II mimics with the selected substrates clearly confirmed the outstanding oxidizing capability of the HRP-I mimic, which is significantly higher than that of HRP-II. The experimental study was supported by computational modeling (DFT calculations) of the oxidation mechanism of the selected substrates with the involvement of quartet and doublet HRP-I mimics ((2,4) Cpd I) and the closed-shell triplet spin HRP-II model ((3) Cpd II) as oxidizing species. The significantly lower activation barriers calculated for the oxidation systems involving (2,4) Cpd I than those found for (3) Cpd II are in line with the much higher oxidizing efficiency of the HRP-I mimic proven in the experimental part of the study. In addition, the DFT calculations show that all three reaction types catalyzed by HRP-I occur on the doublet spin surface in an effectively concerted manner, whereas these reactions may proceed in a stepwise mechanism with the HRP-II mimic as oxidant. However, the high desaturation or oxygen rebound barriers during CH bond activation processes by the HRP-II mimic predict a sufficient lifetime for the substrate radical formed through hydrogen abstraction. Thus, the theoretical calculations suggest that the dissociation of the substrate radical may be a more favorable pathway than desaturation or oxygen rebound processes. Importantly, depending on the electronic nature of the oxidizing species, that is, (2,4) Cpd I or (3) Cpd II, an interesting region-selective conversion phenomenon between sulfoxidation and H-atom abstraction was revealed in the course of the oxidation reaction of dimethylsulfide. The combined experimental and theoretical study on the elucidation of the intrinsic reactivity patterns of the HRP-I and HRP-II mimics provides a valuable tool for evaluating the particular role of the HRP active species in biological systems.
authors.affiliation: Inorganic Chemistry, Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Egerlandstrasse 1, 91058 Erlangen (Germany); College of Environmental and Resource Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058 (China).
authors.forename: Li
authors.initials: L
authors.lastname: Ji
authors.forename: Alicja
authors.initials: A
authors.lastname: Franke
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Brindell
authors.forename: Maria
authors.initials: M
authors.lastname: Oszajca
authors.forename: Achim
authors.initials: A
authors.lastname: Zahl
authors.forename: Rudi
authors.initials: R
authors.lastname: van Eldik
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D006735:Horseradish Peroxidase / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D013816:Thermodynamics
chemical_list: C098326:oxyferryl porphyrin pi cation radical; D006735:Horseradish Peroxidase
keywords: UV/Vis spectroscopy; compound I; compound II; horseradish peroxidase; kinetics