SUPPORTING INFORMATION
Prediction of Activation Energies for Hydrogen Abstraction by Cytochrome P450 Lars Olsen,*,† Patrik Rydberg,‡ Thomas. H. Rod,§ and Ulf Ryde‡
Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, 2 Universitetsparken, DK-2100 Copenhagen, Denmark, Department of Theoretical Chemistry, University of Lund, Sweden, and Atomistix A/S, Nano-Science Center, Niels Bohr Institute, Juliane Maries Vej 30, DK-2100 Copenhagen, Denmark.
Table of contents: S1. Transition states obtained with small organic radical models of compound I at the B3LYP level. ..S2 S2. Transition states obtained with small organic radical models of compound I at the AM1 level........S3
* To whom correspondence should be addressed. Phone: (+45) 35 30 63 05, Fax: (+45) 35 30 60 40, Email:
[email protected], † Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Denmark, ‡ Department of Theoretical Chemistry, University of Lund, Sweden, § Atomistix A/S, Denmark
S1
Table S1. Transition states obtained with small organic radical models of compound I at the B3LYP level.a p-nitrosophenoxy phenoxy Substrate Energy O–H C–H Energy O–H 1 Methane 140.53 1.16 1.38 105.03 1.12 2 Propane(1) 121.28 1.19 1.36 87.47 1.14 3 Propane(2) 105.63 1.22 1.33 72.14 1.17 4 Isobutane 95.26 1.23 1.33 62.03 1.18 5 Propene 92.59 1.24 1.33 59.66 1.21 6 Propionaldehyde 104.82 1.21 1.35 67.53 1.19 7 Toluene 91.60 1.23 1.34 60.24 1.19 8 Ethylbenzene(2) 84.73 1.25 1.32 54.55 1.22 9 1-Methylethylbenzene 84.29 1.27 1.30 54.40 1.23 10 Methoxymethane 96.11 1.25 1.32 65.71 1.20 11 Dimethylsulfane 85.87 1.23 1.33 57.91 1.18 12 Methyl(phenyl)sulfane 84.82 1.19 1.38 55.93 1.15 13 Dimethylamine 63.55 1.32 1.28 39.68 1.25 14 Trimethylamine 57.48 1.33 1.28 36.11 1.25 15 Fluoroethane (2) 128.14 1.16 1.39 94.26 1.13 16 Fluoroethane (1) 112.05 1.20 1.34 78.22 1.16 17 Ethylbenzene(2) 120.57 1.20 1.35 86.68 1.14 18 2-fluoroprop-1-ene 102.35 1.24 1.33 64.72 1.20 19 prop-1-en-2-ol 97.07 1.21 1.37 67.26 1.21 20 p-xylene 87.34 1.23 1.34 58.27 1.20 21 1-methyl-4-nitrosobenzene 100.87 1.20 1.36 62.18 1.18 22 methoxybenzene 99.44 1.23 1.33 68.34 1.17 d 66.27 1.27 1.31 40.99 1.21 23 N-methylaniline 24 N,N-dimethylaniline 59.67 1.30 1.30 38.64 1.24 a Energies in kJ/mole, distances in Å.
C–H 1.44 1.41 1.38 1.37 1.35 1.37 1.37 1.34 1.33 1.36 1.38 1.41 1.33 1.32 1.43 1.39 1.41 1.37 1.38 1.36 1.39 1.39 1.36 1.34
Energy 44.07 30.54 18.33 10.72 15.91 18.57 13.27 9.34 8.41 13.81 9.69 6.92 -6.16 -7.78 35.78 21.53 29.18 18.84 18.44 12.15 17.37 15.82 -3.13 -4.34
methoxy O–H 1.16 1.20 1.24 1.28 1.31 1.28 1.29 1.32 1.32 1.28 1.27 1.26 1.35 1.36 1.18 1.22 1.20 1.27 1.30 1.30 1.27 1.25 1.32 1.35
S2
C–H 1.35 1.32 1.28 1.26 1.25 1.26 1.27 1.24 1.24 1.28 1.27 1.28 1.24 1.24 1.34 1.30 1.32 1.27 1.28 1.26 1.27 1.28 1.25 1.24
Table S2. Transition states obtained with small organic radical models of compound I at the AM1 level.a p-nitrosophenoxy phenoxy Substrate Energy O–H C–H Energy O–H 1 Methane 133.70 1.21 1.30 137.82 1.21 2 Propane(1) 125.36 1.24 1.30 129.90 1.23 3 Propane(2) 116.60 1.27 1.30 121.64 1.26 4 Isobutane 112.23 1.29 1.30 116.95 1.28 5 Propene 113.19 1.28 1.29 117.57 1.27 6 Propionaldehyde 118.40 1.24 1.32 120.49 1.23 7 Toluene 110.48 1.28 1.29 115.06 1.27 8 Ethylbenzene(2) 106.69 1.30 1.29 111.75 1.29 9 1-Methylethylbenzene 107.80 1.31 1.30 112.42 1.30 10 Methoxymethane 112.48 1.27 1.28 117.22 1.26 11 Dimethylsulfane 108.30 1.30 1.28 113.94 1.28 12 Methyl(phenyl)sulfane 108.10 1.30 1.28 113.45 1.28 13 Dimethylamine 95.37 1.34 1.27 101.49 1.31 14 Trimethylamine 97.53 1.33 1.27 103.90 1.31 15 Fluoroethane (2) 129.10 1.23 1.31 132.64 1.22 16 Fluoroethane (1) 111.22 1.27 1.30 114.60 1.26 17 Ethylbenzene(2) 125.61 1.24 1.30 129.74 1.23 18 2-fluoroprop-1-ene 116.78 1.27 1.30 120.06 1.26 19 prop-1-en-2-ol 113.78 1.28 1.29 117.25 1.26 20 p-xylene 109.11 1.28 1.29 113.88 1.27 21 1-methyl-4-nitrosobenzene 149.49 1.24 1.32 117.81 1.25 22 methoxybenzene 114.94 1.26 1.29 119.23 1.25 23 N-methylanilined 97.49 1.33 1.27 103.45 1.30 24 N,N-dimethylaniline 97.34 1.33 1.27 103.62 1.30 a Energies in kJ/mole, distances in Å.
C–H 1.31 1.31 1.30 1.31 1.30 1.33 1.30 1.30 1.31 1.29 1.29 1.29 1.28 1.28 1.31 1.31 1.31 1.30 1.30 1.30 1.31 1.30 1.28 1.28
methoxy Energy O–H 75.44 1.29 70.19 1.32 64.77 1.35 61.92 1.37 63.03 1.36 63.89 1.32 59.97 1.36 58.45 1.38 59.58 1.39 59.30 1.35 61.18 1.37 60.67 1.36 48.09 1.40 50.46 1.40 72.38 1.30 59.13 1.35 70.05 1.31 64.96 1.34 62.32 1.34 58.94 1.36 63.56 1.34 61.57 1.34 51.15 1.40 50.81 1.40
S3
C–H 1.24 1.24 1.24 1.24 1.23 1.25 1.23 1.24 1.25 1.23 1.23 1.23 1.23 1.23 1.24 1.24 1.24 1.24 1.24 1.23 1.24 1.23 1.23 1.23
