Applications of density functional theory to iron-containing molecules of bioinorganic interest

Frontiers in Chemistry

Volumn 2, Issue APR, 2014, Pages

  Hirao, Hajime ^a   Thellamurege, Nandun ^a   Zhang, Xi ^a  

^a NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

Author keywords

Catalysis; Density functional theory; Enzyme reactions; Iron containing molecules; Protein environment; QMMM

Indexed keywords

EID: 84987664719     PISSN: None     EISSN: 22962646     Source Type: Journal    
DOI: 10.3389/fchem.2014.00014     Document Type: Review

References (336)

1. Abu-Omar, M. M., Loaiza, A., and Hontzeas, N. (2005). Reaction mechanisms of mononuclear non-heme iron oxygenases. Chem. Rev. 105, 2227-2252. doi: 10.1021/cr040653o
2. Ackermann, L. (2011). Carboxylate-assisted transition-metal-catalyzed C-H bond functionalizations: mechanism and scope. Chem. Rev. 111, 1315-1345. doi: 10.1021/cr100412j
3. ADF2012.01. (2012). SCM Theoretical Chemistry. Amsterdam: Vrije Universiteit. Available online at: http://www.scm.com
4. Altun, A., Guallar, V., Friesner, R. A., Shaik, S., and Thiel, W. (2006). The effect of heme environment on the hydrogen abstraction reaction of camphor in P450cam catalysis: a QM/MM study. J. Am. Chem. Soc. 128, 3924-3925. doi: 10.1021/ja058196w
5. Altun, A., Kumar, D., Neese, F., and Thiel, W. (2008). Multireference ab initio quantum mechanics/molecular mechanics study on intermediates in the catalytic cycle of cytochrome P450cam. J. Phys. Chem. A 112, 12904-12910. doi: 10.1021/jp802092w
6. Altun, A., Shaik, S., and Thiel, W. (2007). What is the active species of cytochrome P450 during camphor hydroxylation? QM/MM studies of different electronic states of compound I and of reduced and oxidized iron-oxo intermediates. J. Am. Chem. Soc. 129, 8978-8987. doi: 10.1021/ja066847y
7. Altun, A., and Thiel, W. (2005). Combined quantum mechanical/molecular mechanical study on the pentacoordinated ferric and ferrous cytochrome P450cam complexes. J. Phys. Chem. B 109, 1268-1280. doi: 10.1021/jp0459108
8. IV=O and FeV=O intermediates. J. Am. Chem. Soc. 135, 4235-4249. doi: 10.1021/ja307077f
9. Bach, R. D., and Dmitrenko, O. (2006). The "somersault" mechanism for the P-450 hydroxylation of hydrocarbons. The intervention of transient inverted metastable hydroperoxides. J. Am. Chem. Soc. 128, 1474-1488. doi: 10.1021/ja052111+
10. Baerends, E. J., and Gritsenko, O. V. (1997). A quantum chemical view of density functional theory. J. Phys. Chem. A 101, 5383-5403. doi: 10.1021/jp9703768
11. Baik, M.-H., Newcomb, M., Friesner, R. A., and Lippard, S. J. (2003). Mechanistic studies on the hydroxylation of methane by methane monooxygenase. Chem. Rev. 103, 2385-2420. doi: 10.1021/cr950244f
12. Balcells, D., Clot, E., and Eisenstein, O. (2010). C-H bond activation in transition metal species from a computational perspective. Chem. Rev. 110, 749-823. doi: 10.1021/cr900315k
13. Bassan, A., Blomberg, M. R. A., Siegbahn, P. E. M., and Que, L. Jr. (2002). A density functional study of O-O bond cleavage for a biomimetic non-heme iron complex demonstrating an FeV-intermediate. J. Am. Chem. Soc. 124, 11056-11063. doi: 10.1021/ja026488g
14. Bassan, A., Blomberg, M. R. A., Siegbahn, P. E. M., and Que, L. Jr. (2005a). A density functional study of a biomimetic non-heme iron catalyst: insights into alkane hydroxylation by a formally HO-FeV=O oxidant. Chem. Eur. J. 11, 692-705. doi: 10.1002/chem.200400383
15. Bassan, A., Blomberg, M. R. A., Siegbahn, P. E. M., and Que, L. Jr. (2005b). Two faces of a biomimetic non-heme HO-FeV=O oxidant: olefin epoxidation versus cis-dihydroxylation. Angew. Chem. Int. Ed. Engl. 44, 2939-2941. doi: 10.1002/anie.200463072
16. Bathelt, C. M., Mulholland, A. J., and Harvey, J. N. (2008). QM/MM modeling of benzene hydroxylation in human cytochrome P450 2C9. J. Phys. Chem. A 112, 13149-13156. doi: 10.1021/jp8016908
17. Bathelt, C. M., Zurek, J., Mulholland, A. J., and Harvey, J. N. (2005). Electronic structure of compound I in human isoforms of cytochrome P450 from QM/MM modeling. J. Am. Chem. Soc. 127, 12900-12908. doi: 10.1021/ja0520924
18. 2. Angew. Chem. Int. Ed. Engl. 45, 5681-5684. doi: 10.1002/anie.200601134
19. Bergman, R. G. (2007). Organometallic chemistry: C-H activation. Nature 446, 391-393. doi: 10.1038/446391a
20. 2+. Eur. J. Inorg. Chem. 2008, 1672-1681. doi: 10.1002/ejic.200701135
21. Bernasconi, L., and Baerends, E. J. (2013). A frontier orbital study with ab initio molecular dynamics of the effects of solvation on chemical reactivity: solvent-induced orbital control in FeO-activated hydroxylation reactions. J. Am. Chem. Soc. 135, 8857-8867. doi: 10.1021/ja311144d
22. 2 in aqueous Fe(II)/EDTA solutions: thermodynamics and electronic structure. Phys. Chem. Chem. Phys. 13, 15272-15282. doi: 10.1039/c1cp21244c
23. Bernasconi, L., Louwerse, M. J., and Baerends, E. J. (2007). The role of equatorial and axial ligands in promoting the activity of non-heme oxidoiron(IV) catalysts in alkane hydroxylation. Eur. J. Inorg. Chem. 2007, 3023-3033. doi: 10.1002/ejic.200601238
24. Berry, J. F., Bill, E., Bothe, E., Neese, F., and Wieghardt, K. (2006). Octahedral non-heme oxo and non-oxo Fe(IV) complexes: an experimental/theoretical comparison. J. Am. Chem. Soc. 128, 13515-13528. doi: 10.1021/ja063590v
25. 2 and C-H activation at a nonheme diiron cluster. Dalton Trans. 905-914. doi: 10.1039/b811885j
26. Bollinger, J. M. Jr., and Krebs, C. (2006). Stalking intermediates in oxygen activation by iron enzymes: motivation and method. J. Inorg. Biochem. 100, 586-605. doi: 10.1016/j.jinorgbio.2006.01.022
27. Bollinger, J. M. Jr., and Krebs, C. (2007). Enzymatic C-H activation by metal-superoxo intermediates. Curr. Opin. Chem. Biol. 11, 151-158. doi: 10.1016/j.cbpa.2007.02.037
28. Bukowski, M. R., Koehntop, K. D., Stubna, A., Bominaar, E. L., Halfen, J. A., Münck, E., et al. (2005). A thiolate-ligated nonheme oxoiron(IV) complex relevant to cytochrome P450. Science 310, 1000-1002. doi: 10.1126/science.1119092
29. Burke, K. (2012). Perspective on density functional theory. J. Chem. Phys. 136, 150901. doi: 10.1063/1.4704546
30. Castro, L., and Bühl, M. (2014). Calculations of one-electron redox potentials of oxoiron(IV) porphyrin complexes. J. Chem. Theory Comput. 10, 243-251. doi: 10.1021/ct400975w
31. Chandrasekaran, P., Stieber, S. C. E., Collins, T. J., Que, L. Jr., Neese, F., and Debeer, S. (2011). Prediction of high-valent iron K-edge absorption spectra by time-dependent density functional theory. Dalton Trans. 40, 11070-11079. doi: 10.1039/c1dt11331c
32. Chen, H., Cho, K.-B., Lai, W., Nam, W., and Shaik, S. (2012). Dioxygen activation by a non-heme iron(II) complex: theoretical study toward understanding ferric-superoxo complexes. J. Chem. Theory Comput. 8, 915-926. doi: 10.1021/ct300015y
33. Chen, H., Hirao, H., Derat, E., Schlichting, I., and Shaik, S. (2008). Quantum mechanical/molecular mechanical study on the mechanisms of compound I formation in the catalytic cycle of chloroperoxidase: an overview on heme enzymes. J. Phys. Chem. B 112, 9490-9500. doi: 10.1021/jp803010f
34. Chen, H., Lai, W. Z., Yao, J. N., and Shaik, S. (2011). Perferryl FeV-oxo nonheme complexes: do they have high-spin or low-spin ground states? J. Chem. Theory Comput. 7, 3049-3053. doi: 10.1021/ct200614g
35. Chen, H., Song, J. S., Lai, W. Z., Wu, W., and Shaik, S. (2010). Multiple low-lying states for compound I of P450cam and chloroperoxidase revealed from multireference ab initio QM/MM calculations. J. Chem. Theory Comput. 6, 940-953. doi: 10.1021/ct9006234
36. Chen, M. S., and White, M. C. (2007). A predictably selective aliphatic C-H oxidation reaction for complex molecule synthesis. Science 318, 783-787. doi: 10.1126/science.1148597
37. Cho, J., Jeon, S., Wilson, S. A., Liu, L. V., Kang, E. A., Braymer, J. J., et al. (2011a). Structure and reactivity of a mononuclear non-haem iron(III)-peroxo complex. Nature 478, 502-505. doi: 10.1038/nature10535
38. 2 binding and spin inversion probability matter. Chem. Commun. 48, 2189-2191. doi: 10.1039/c2cc17610f
39. Cho, K.-B., Hirao, H., Chen, H., Carvajal, M. A., Cohen, S., Derat, E., et al. (2008). Compound I in heme thiolate enzymes: a comparative QM/MM study. J. Phys. Chem. A 112, 13128-13138. doi: 10.1021/jp806770y
40. IV=O species. Chem. Eur. J. 18, 10444-10453. doi: 10.1002/chem.201200096
41. Cho, K.-B., Lai, W., Hamberg, M., Raman, C., and Shaik, S. (2011b). The reaction mechanism of allene oxide synthase: interplay of theoretical QM/MM calculations and experimental investigations. Arch. Biochem. Biophys. 507, 14-25. doi: 10.1016/j.abb.2010.07.016
42. Cho, K.-B., Shaik, S., and Nam, W. (2010). Theoretical predictions of a highly reactive non-heme Fe(IV)=O complex with a high-spin ground state. Chem. Commun. 46, 4511-4513. doi: 10.1039/c0cc00292e
43. IVO complexes. J. Am. Chem. Soc. 134, 20222-20225. doi: 10.1021/ja308290r
44. Chung, L. W., Hirao, H., Li, X., and Morokuma, K. (2011a). The ONIOM method: its foundation and applications to metalloenzymes and photobiology. WIREs Comput. Mol. Sci. 2, 327-350. doi: 10.1002/wcms.85
45. Chung, L. W., Li, X., Hirao, H., and Morokuma, K. (2011b). Comparative reactivity of ferric-superoxo and ferryl-oxo species in heme and non-heme complexes. J. Am. Chem. Soc. 133, 20076-20079. doi: 10.1021/ja2084898
46. Cicchillo, R. M., Zhang, H., Blodgett, J. A. V., Whitteck, J. T., Li, G., Nair, S. K., et al. (2009). An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis. Nature 459, 871-874. doi: 10.1038/nature07972
47. Claeyssens, F., Harvey, J. N., Manby, F. R., Mata, R. A., Mulholland, A. J., Ranaghan, K. E., et al. (2006). High-accuracy computation of reaction barriers in enzymes. Angew. Chem. Int. Ed. Engl. 45, 6856-6859. doi: 10.1002/anie.200602711
48. Cohen, A. J., Mori-Sánchez, P., and Yang, W. (2012). Challenges for density functinoal theory. Chem. Rev. 112, 289-320. doi: 10.1021/cr200107z
49. Cohen, S., Kumar, D., and Shaik, S. (2006). In silico design of a mutant of cytochrome P450 containing selenocysteine. J. Am. Chem. Soc. 128, 2649-2653. doi: 10.1021/ja056586c
50. Comba, P., Maurer, M., and Vadivelu, P. (2008). Oxidation of cyclohexane by a high-valent iron bispidine complex: a combined experimental and computational mechanistic study. J. Phys. Chem. A 112, 13028-13036. doi: 10.1021/jp8037895
51. Costas, M., Chen, K., and Que, L. Jr. (2000). Biomimetic nonheme iron catalysts for alkane hydroxylation. Coord. Chem. Rev. 200-202, 517-544. doi: 10.1016/S0010-8545(00)00320-9
52. Costas, M., Mehn, M. P., Jensen, M. P., and Que, L. Jr. (2004). Dioxygen activation at mononuclear nonheme iron active sites: enzymes, models, and intermediates. Chem. Rev. 104, 939-986. doi: 10.1021/cr020628n
53. Cramer, C. J., and Truhlar, D. G. (2009). Density functional theory for transition metals and transitionmetal chemistry. Phys. Chem. Chem. Phys. 11, 10757-10816. doi: 10.1039/b907148b
54. Cui, Q., Elstner, M., Kaxiras, E., Frauenheim, T., and Karplus, M. (2001). A QM/MM implementation of the self-consistent charge density functional tight binding (SCC-DFTB) method. J. Phys. Chem. B 105, 569-585. doi: 10.1021/jp0029109
55. Cui, Q., and Karplus, M. (2002). Quantum mechanics/molecular mechanics studies of triosephosphate isomerase-catalyzed reactions: effect of geometry and tunneling on proton-transfer rate constants. J. Am. Chem. Soc. 124, 3093-3124. doi: 10.1021/ja0118439
56. Davies, H. M. L., and Manning, J. R. (2008). Catalytic C-H functionalization by metal carbenoid and nitrenoid insertion. Nature 451, 417-424. doi: 10.1038/nature06485
57. Davydov, R., Makris, T. M., Kofman, V., Werst, D. E., Sligar, S. G., and Hoffman, B. M. (2001). Hydroxylation of camphor by reduced oxy-cytochrome P450cam: mechanistic implications of EPR and ENDOR studies of catalytic intermediates in native and mutant enzymes. J. Am. Chem. Soc. 123, 1403-1415. doi: 10.1021/ja003583l
58. Dawson, J. H., and Sono, M. (1987). Cytochrome P-450 and chloroperoxidase: thiolate-ligated heme enzymes. Spectroscopic determination of their active-site structures and mechanistic implications of thiolate ligation. Chem. Rev. 87, 1255-1276. doi: 10.1021/cr00081a015
59. de Visser, S. P. (2006). What factors influence the ratio of C-H hydroxylation versus C=C epoxidation by a nonheme cytochrome P450 biomimetic? J. Am. Chem. Soc. 128, 15809-15818. doi: 10.1021/ja065365j
60. de Visser, S. P. (2010). Trends in substrate hydroxylation reactions by heme and nonheme iron(IV)-oxo oxidants give correlations between intrinsic properties of the oxidant with barrier height. J. Am. Chem. Soc. 132, 1087-1097. doi: 10.1021/ja908340j
61. de Visser, S. P., Kumar, D., and Shaik, S. (2004). How do aldehyde side products occur during alkene epoxidation by cytochrome P450? Theory reveals a state-specific multi-state scenario where the high-spin component leads to all side products. J. Inorg. Biochem. 98, 1183-1193. doi: 10.1016/j.jinorgbio.2004.01.015
62. de Visser, S. P., Latifi, R., Tahsini, L., and Nam, W. (2011). The axial ligand effect on aliphatic and aromatic hydroxylation by non-heme iron(IV)-oxo biomimetic complexes. Chem. Asian J. 6, 493-504. doi: 10.1002/asia.201000586
63. de Visser, S. P., Ogliaro, F., Sharma, P. K., and Shaik, S. (2002). What factors affect the regioselectivity of oxidation by cytochrome P450? A DFT study of allylic hydroxylation and double bond epoxidation in a model reaction. J. Am. Chem. Soc. 124, 11809-11826. doi: 10.1021/ja026872d
64. de Visser, S. P., Oh, K., Han, A. R., and Nam, W. (2007). Combined experimental and theoretical study on aromatic hydroxylation by mononuclear nonheme iron(IV)-oxo complexes. Inorg. Chem. 46, 4632-4641. doi: 10.1021/ic700462h
65. de Visser, S. P., Rohde, J. U., Lee, Y. M., Cho, J., and Nam, W. (2013). Intrinsic properties and reactivities of mononuclear nonheme iron-oxygen complexes bearing the tetramethylcyclam ligand. Coord. Chem. Rev. 257, 381-393. doi: 10.1016/j.ccr.2012.06.002
66. IV=O complexes: Fe-O bonding and its contributions to reactivity. J. Am. Chem. Soc. 129, 15983-15996. doi: 10.1021/ja074900s
67. IV=O heme and non-heme species: electronic structures, bonding, and reactivities. Angew. Chem. Int. Ed. Engl. 44, 2252-2255. doi: 10.1002/anie.200462182
68. Denisov, I. G., Makris, T. M., Sligar, S. G., and Schlichting, I. (2005). Structure and chemistry of cytochrome P450. Chem. Rev. 105, 2253-2278. doi: 10.1021/cr0307143
69. Derat, E., Kumar, D., Hirao, H., and Shaik, S. (2006). Gauging the relative oxidative powers of compound I, ferric-hydroperoxide, and the ferric-hydrogen peroxide species of cytochrome P450 toward C-H hydroxylation of a radical clock substrate. J. Am. Chem. Soc. 128, 473-484. doi: 10.1021/ja056328f
70. Derat, E., and Shaik, S. (2006). The Poulos-Kraut mechanism of compound I formation in horseradish peroxidase: a QM/MM study. J. Phys. Chem. B 110, 10526-10533. doi: 10.1021/jp055412e
71. IV=O oxidants. Angew. Chem. Int. Ed. Engl. 47, 3356-3359. doi: 10.1002/anie.200705880
72. Dumas, V. G., Defelipe, L. A., Petruk, A. A., Turjanski, A. G., and Marti, M. A. (2013). QM/MM study of the C-C coupling reaction mechanism of CYP121, an essential cytochrome p450 of Mycobacterium tuberculosis. Proteins. doi: 10.1002/prot.24474
73. Feig, A. L., and Lippard, S. J. (1994). Reactions of non-heme iron(II) centers with dioxygen in biology and chemistry. Chem. Rev. 94, 759-805. doi: 10.1021/cr00027a011
74. Feixas, F., Solà, M., and Swart, M. (2009). Chemical bonding and aromaticity in metalloporphyrins. Can. J. Chem. 87, 1063-1073. doi: 10.1139/V09-037
75. Fiedler, A. T., and Que, L. Jr. (2009). Reactivities of Fe(IV) complexes with oxo, hydroxo, and alkylperoxo ligands: an experimental and computational study. Inorg. Chem. 48, 11038-11047. doi: 10.1021/ic901391y
76. Field, M. J., Bash, P. A., and Karplus, M. (1990). A combined quantum mechanical and molecular mechanical potential for molecular dynamics simulations. J. Comput. Chem. 11, 700-733. doi: 10.1002/jcc.540110605
77. Fishelovitch, D., Hazan, C., Hirao, H., Wolfson, H. J., Nussinov, R., and Shaik, S. (2007). QM/MM study of the active species of the human cytochrome P450 3A4, and the influence thereof of the multiple substrate binding. J. Phys. Chem. B 111, 13822-13832. doi: 10.1021/jp076401j
78. Friedle, S., Reisner, E., and Lippard, S. J. (2010). Current challenges of modeling diiron enzyme active sites for dioxygenactivation by biomimetic synthetic complexes. Chem. Soc. Rev. 39, 2768-2779. doi: 10.1039/c003079c
79. Friesner, R. A., and Guallar, V. (2005). Ab initio quantum chemical and mixed quantum mechanics/molecular mechanics (QM/MM) methods for studying enzymatic catalysis. Annu. Rev. Phys. Chem. 56, 389-427. doi: 10.1146/annurev.physchem.55.091602.094410
80. Gao, J. (1996). Hybrid quantum and molecular mechanical simulations: an alternative avenue to solvent effects in organic chemistry. Acc. Chem. Res. 29, 298-305. doi: 10.1021/ar950140r
81. Geng, C., Ye, S., and Neese, F. (2010). Analysis of reaction channels for alkane hydroxylation by nonheme iron(IV)-oxo complexes. Angew. Chem. Int. Ed. Engl. 49, 5717-5720. doi: 10.1002/anie.201001850
82. Godula, K., and Sames, D. (2006). C-H bond functionalization in complex organic synthesis. Science 312, 67-72. doi: 10.1126/science.1114731
83. Goldberg, K. I., and Goldman, A. S. (2004). "Activation and functionalization of C-H bonds, " in ACS Symposium Series, Vol. 885 (Washington, DC: American Chemical Society). doi: 10.1021/bk-2004-0885
84. Gonzalez-Ovalle, L. E., Quesne, M. G., Kumar, D., Goldberg, D. P., and de Visser, S. P. (2012). Axial and equatorial ligand effects on biomimetic cysteine dioxygenase model complexes. Org. Biomol. Chem. 10, 5401-5409. doi: 10.1039/c2ob25406a
85. 2+. Inorg. Chem. 51, 63-75. doi: 10.1021/ic200754w
86. Gordon, M. S., and Schmidt, M. W. (2005). "Advances in electronic structure theory: GAMESS a decade later, " in Theory and Applications of Computational Chemistry, eds C. E. Dykstra, K. S. Frenking, and G. E. Scuseria (Amsterdam: Elsevier).
87. Green, M. T., Dawson, J. H., and Gray, H. B. (2004). Oxoiron(IV) in chloroperoxidase compound II is basic: implications for P450 chemistry. Science 304, 1653-1656. doi: 10.1126/science.1096897
88. Grimme, S. (2006). Semiempirical GGA-type density functional constructed with a long-range dispersion correction. J. Comput. Chem. 27, 1787-1799. doi: 10.1002/jcc.20495
89. Groves, J. T. (1985). Key elements of the chemistry of cytochrome P-450: the oxygen rebound mechanism. J. Chem. Educ. 62, 928-931. doi: 10.1021/ed062p928
90. Groves, J. T. (2006). High-valent iron in chemical and biological oxidations. J. Inorg. Biochem. 100, 434-447. doi: 10.1016/j.jinorgbio.2006.01.012
91. Groves, J. T. (2014). Enzymatic C-H bond activation: using push to get pull. Nat. Chem. 6, 89-91. doi: 10.1038/nchem.1855
92. Groves, J. T., McClusky, G. A., White, R. E., and Coon, M. J. (1978). Aliphatic hydroxylation by highly purified liver microsomal cytochrome P-450. Evidence for a carbon radical intermediate. Biochem. Biophys. Res. Commun. 81, 154-160. doi: 10.1016/0006-291X(78)91643-1
93. Guallar, V., and Friesner, R. A. (2004). Cytochrome P450CAM enzymatic catalysis cycle: a quantum mechanics/molecular mechanics study. J. Am. Chem. Soc. 126, 8501-8508. doi: 10.1021/ja036123b
94. Guengerich, F. P. (2001). Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 14, 611-650. doi: 10.1021/tx0002583
95. Guengerich, F. P. (2008). Cytochrome P450 and chemical toxicology. Chem. Res. Toxicol. 21, 70-83. doi: 10.1021/tx700079z
96. Guengerich, F. P. (2013). New trends in cytochrome P450 research at the half-century mark. J. Biol. Chem. 288, 17063-17064. doi: 10.1074/jbc.R113.466821
97. Hackett, J. C., Brueggemeier, R. W., and Hadad, C. M. (2005). The final catalytic step of cytochrome P450 aromatase: a density functional theory study. J. Am. Chem. Soc. 127, 5224-5237. doi: 10.1021/ja044716w
98. Hackett, J. C., Sanan, T. T., and Hadad, C. M. (2007). Oxidative dehalogenation of perhalogenated benzenes by cytochrome P450 compound I. Biochemistry 46, 5924-5940. doi: 10.1021/bi700365x
99. Hammes-Schiffer, S. (2013). Catalytic efficiency of enzymes: a theoretical analysis. Biochemistry 52, 2012-2020. doi: 10.1021/bi301515j
100. Hammes-Schiffer, S., Hatcher, E., Ishikita, H., Skone, J. H., and Soudackov, A. V. (2008). Theoretical studies of proton-coupled electron transfer: models and concepts relevant to bioenergetics. Coord. Chem. Rev. 252, 384-394. doi: 10.1016/j.ccr.2007.07.019
101. Hammes-Schiffer, S., and Soudackov, A. V. (2008). Proton-coupled electron transfer in solution, proteins, and electrochemistry. J. Phys. Chem. B 112, 14108-14123. doi: 10.1021/jp805876e
102. Hanson, K. L., VandenBrink, B. M., Babu, K. N., Allen, K. E., Nelson, W. L., and Kunze, K. L. (2010). Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (S)-fluoxetine, and N-desmethyldiltiazem. Drug Metab. Dispos. 38, 963-972. doi: 10.1124/dmd.110.032391
103. Harvey, J. N. (2006). On the accuracy of density functional theory in transition metal chemistry. Annu. Rep. Prog. Chem. Sect. C 102, 203-226. doi: 10.1039/b419105f
104. Harvey, J. N., Bathelt, C. M., and Mulholland, A. J. (2006). QM/MM modeling of compound I active species in cytochrome P450, cytochrome C peroxidase, and ascorbate peroxidase. J. Comput. Chem. 27, 1352-1362. doi: 10.1002/jcc.20446
105. Hatcher, E., Soudackov, A. V., and Hammes-Schiffer, S. (2004). Proton-coupled electron transfer in soybean lipoxygenase. J. Am. Chem. Soc. 126, 5763-5775. doi: 10.1021/ja039606o
106. Hegg, E. L., and Que, L. Jr. (1997). The 2-his-1-carboxylate facial triad-an emerging structural motif in mononuclear non-heme iron(II) enzymes. Eur. J. Biochem. 250, 625-629. doi: 10.1111/j.1432-1033.1997.t01-1-00625.x
107. Himo, F., and Siegbahn, P. E. M. (2003). Quantum chemical studies of radical-containing enzymes. Chem. Rev. 103, 2421-2456. doi: 10.1021/cr020436s
108. Hirao, H. (2011a). Energy decomposition analysis of the protein environmental effect: the case of cytochrome P450cam compound I. Chem. Lett. 40, 1179-1181. doi: 10.1246/cl.2011.1179
109. Hirao, H. (2011b). The effects of protein environment and dispersion on the formation of ferric-superoxide species in myo-inositol oxygenase (MIOX): a combined ONIOM(DFT:MM) and energy decomposition analysis. J. Phys. Chem. B 115, 11278-11285. doi: 10.1021/jp2057173
110. Hirao, H., and Morokuma, K. (2009). Insights into the (superoxo)Fe(III)Fe(III) intermediate and reaction mechanism of myo-inositol oxygenase: DFT and ONIOM(DFT:MM) study. J. Am. Chem. Soc. 131, 17206-17214. doi: 10.1021/ja905296w
111. Hirao, H., and Morokuma, K. (2010a). Ferric superoxide and ferric hydroxide are used in the catalytic mechanism of hydroxyethylphosphonate dioxygenase: a density functional theory investigation. J. Am. Chem. Soc. 132, 17901-17909. doi: 10.1021/ja108174d
112. Hirao, H., and Morokuma, K. (2010b). What is the real nature of ferrous soybean lipoxygenase-1? A new two-conformation model based on combined ONIOM(DFT:MM) and multireference configuration interaction characterization. J. Phys. Chem. Lett. 1, 901-906. doi: 10.1021/jz1001456
113. Hirao, H., and Morokuma, K. (2011a). Recent progress in the theoretical studies of structure, function, and reaction of biological molecules. Yakugaku Zasshi 131, 1151-1161. doi: 10.1248/yakushi.131.1151
114. Hirao, H., and Morokuma, K. (2011b). ONIOM(DFT:MM) study of 2-hydroxyethylphosphonate dioxygenase: what determines the destinies of different substrates? J. Am. Chem. Soc. 133, 14550-14553. doi: 10.1021/ja206222f
115. Hirao, H., Chen, H., Carvajal, M. A., Wang, Y., and Shaik, S. (2008b). Effect of external electric fields on the C-H bond activation reactivity of nonheme iron-oxo reagents. J. Am. Chem. Soc. 130, 3319-3327. doi: 10.1021/ja070903t
116. Hirao, H., Cheong, Z. H., and Wang, X. (2012). Pivotal role of water in terminating enzymatic function: a density functional theory study of the mechanism-based inactivation of cytochromes P450. J. Phys. Chem. B 116, 7787-7794. doi: 10.1021/jp302592d
117. Hirao, H., Cho, K.-B., and Shaik, S. (2008c). QM/MM theoretical study of the pentacoordinate Mn(III) and resting states of manganese-reconstituted cytochrome P450cam. J. Biol. Inorg. Chem. 13, 521-530. doi: 10.1007/s00775-007-0340-9
118. Hirao, H., Chuanprasit, P., Cheong, Y. Y., and Wang, X. (2013a). How is a metabolic intermediate formed in the mechanism-based inactivation of cytochrome P450 by using 1, 1-dimethylhydrazine: hydrogen abstraction or N-nitrogen oxidation? Chem. Eur. J. 19, 7361-7369. doi: 10.1002/chem.201300689
119. Hirao, H., Kumar, D., Que, L. Jr., and Shaik, S. (2006a). Two-state reactivity in alkane hydroxylation by non-heme iron-oxo complexes. J. Am. Chem. Soc. 128, 8590-8606. doi: 10.1021/ja061609o
120. Hirao, H., Kumar, D., and Shaik, S. (2006b). On the identity and reactivity patterns of the "second oxidant" of the T252A mutant of cytochrome P450cam in the oxidation of 5-methylenenylcamphor. J. Inorg. Biochem. 100, 2054-2068. doi: 10.1016/j.jinorgbio.2006.09.001
121. Hirao, H., Kumar, D., Thiel, W., and Shaik, S. (2005). Two states and two more in the mechanisms of hydroxylation and epoxidation by cytochrome P450. J. Am. Chem. Soc. 127, 13007-13018. doi: 10.1021/ja053847+
122. 2 and a nonheme iron(II) complex: O-O cleavage involving proton-coupled electron transfer. Inorg. Chem. 50, 6637-6648. doi: 10.1021/ic200522r
123. IV=O oxidants. Chem. Eur. J. 14, 1740-1756. doi: 10.1002/chem.200701739
124. Hirao, H., Thellamurege, N. M., Chuanprasit, P., and Xu, K. (2013b). Importance of H-abstraction in the final step of nitrosoalkane formation in the mechanism-based inactivation of cytochrome P450 by amine-containing drugs. Int. J. Mol. Sci. 14, 24692-24705. doi: 10.3390/ijms141224692
125. Hohenberg, P., and Kohn, W. (1964). Inhomogeneous electron gas. Phys. Rev. B 136, 864-871. doi: 10.1103/PhysRev.136.B864
126. Hohenberger, J., Ray, K., and Meyer, K. (2012). The biology and chemistry of high-valent iron-oxo and iron-nitrido complexes. Nat. Commun. 3, 720. doi: 10.1038/ncomms1718
127. Hong, S., Lee, Y.-M., Cho, K.-B., Seo, M. S., Song, D., Yoon, J., et al. (2014). Conversion of high-spin iron(III)-alkylperoxo to iron(IV)-oxo species via O-O bond homolysis in nonheme iron models. Chem. Sci. 5, 156-162. doi: 10.1039/C3SC52236A
128. Hu, H., and Yang, W. (2008). Free energies of chemical reactions in solution and in enzymes with ab initio quantum mechanics/molecular mechanics methods. Annu. Rev. Phys. Chem. 59, 573-601. doi: 10.1146/annurev.physchem.59.032607.093618
129. Hu, H., and Yang, W. (2009). Development and application of ab initio QM/MM methods for mechanistic simulation of reactions in solution and in enzymes. J. Mol. Struct. Theochem 898, 17-30. doi: 10.1016/j.theochem.2008.12.025
130. Hughes, T. F., and Friesner, R. A. (2012). Development of accurate DFT methods for computing redox potentials of transition metal complexes: results for model complexes and application to cytochrome P450. J. Chem. Theory Comput. 8, 442-459. doi: 10.1021/ct2006693
131. Humbel, S., Sieber, S., and Morokuma, K. (1996). The IMOMO method: integration of different levels of molecular orbital approximations for geometry optimization of large systems: test for n-butane conformation and SN2 reaction: RCl+Cl-. J. Chem. Phys. 105, 1959-1967. doi: 10.1063/1.472065
132. Isin, E. M., and Guengerich, F. P. (2007). Complex reactions catalyzed by cytochrome P450 enzymes. Biochim. Biophys. Acta 1770, 314-329. doi: 10.1016/j.bbagen.2006.07.003
133. Isobe, H., Nishihara, S., Shoji, M., Yamanaka, S., Shimada, J., Hagiwara, M., et al. (2008). Extended Hartree-Fock theory of chemical reactions. VIII. Hydroxylation reactions of chemical reactions by P450. Int. J. Quantum Chem. 108, 2991-3009. doi: 10.1002/qua.21874
134. Isobe, H., Yamaguchi, K., Okumura, M., and Shimada, J. (2012). Role of perferryl-oxo oxidant in alkane hydroxylation catalyzed by cytochrome P450: a hybrid density functional study. J. Phys. Chem. B 116, 4713-4730. doi: 10.1021/jp211184y
135. Isobe, H., Yamanaka, S., Okumura, M., Yamaguchi, K., and Shimada, J. (2011). Unique structural and electronic features of perferryl-oxo oxidant in cytochrome P450. J. Phys. Chem. B 115, 10730-10738. doi: 10.1021/jp206004y
136. Iyengar, S. S., Sumner, I., and Jakowski, J. (2008). Hydrogen tunneling in an enzyme active site: a quantum wavepacket dynamical perspective. J. Phys. Chem. B 112, 7601-7613. doi: 10.1021/jp7103215
137. Jia, C., Kitamura, T., and Fujiwara, Y. (2001). Catalytic functionalization of arenes and alkanes via C-H bond activation. Acc. Chem. Res. 34, 633-639. doi: 10.1021/ar000209h
138. 2+. J. Phys. Chem. C 111, 12397-12406. doi: 10.1021/jp0730444
139. IVO complexes that can oxidize the C-H bonds of cyclohexane at room temperature. J. Am. Chem. Soc. 126, 472-473. doi: 10.1021/ja037288n
140. Kakiuchi, F., and Chatani, N. (2003). Catalytic methods for C-H bond functionalization: application in organic synthesis. Adv. Synth. Catal. 345, 1077-1101. doi: 10.1002/adsc.200303094
141. Kamachi, T., Shiota, Y., Ohta, T., and Yoshizawa, K. (2003). Does the hydroxo species of cytochrome P450 participate in olefein epoxidation with the main oxidant, compund I? Critisism from density functioal calculations. Bull. Chem. Soc. Jpn. 76, 721-732. doi: 10.1246/bcsj.76.721
142. Kamachi, T., and Yoshizawa, K. (2003). A theoretical study on the mechanism of camphor hydroxylation by compound I of cytochrome P450. J. Am. Chem. Soc. 125, 4652-4661. doi: 10.1021/ja0208862
143. Kamerlin, S. C. L., Haranczyk, M., and Warshel, A. (2009). Progress in ab initio QM/MM free-energy simulations of electrostatic energies in proteins: accelerated QM/MM studies of pKa, redox reactions and solvation free energies. J. Phys. Chem. B 113, 1253-1272. doi: 10.1021/jp8071712
144. Karton, A., Tarnopolsky, A., Lamère, J. F., Schatz, G. C., and Martin, J. M. L. (2008). Highly accurate first-principles benchmark data sets for the parametrization and validation of density functional and other approximate methods. Derivation of a robust, generally applicable, double-hybrid functional for thermochemistry and thermochemical kinetics. J. Phys. Chem. A, 112, 12868-12886. doi: 10.1021/jp801805p
145. Kim, S. O., Sastri, C. V., Seo, M. S., Kim, J., and Nam, W. (2005). Dioxygen activation and catalytic aerobic oxidation by a mononuclear nonheme iron(II) complex. J. Am. Chem. Soc., 127, 4178-4179. doi: 10.1021/ja043083i
146. Kim, Y. M., Cho, K.-B., Cho, J., Wang, B., Li, C., Shaik, S., et al. (2013). A mononuclear non-heme high-spin iron(III)-hydroperoxo complex as an active oxidant in sulfoxidation reactions. J. Am. Chem. Soc. 135, 8838-8841. doi: 10.1021/ja404152q
147. Kitaura, K., and Morokuma, K. (1976). A new energy decomposition scheme for molecular interactions within the Hartree-Fock approximation. Int. J. Quantum Chem. 10, 325-340. doi: 10.1002/qua.560100211
148. Klinker, E. J., Shaik, S., Hirao, H., and Que, L. Jr. (2009). A two-state reactivity model explains unusual kinetic isotope effect patterns in C-H bond cleavage by nonheme oxoiron(IV) complexes. Angew. Chem. Int. Ed. Engl. 48, 1291-1295. doi: 10.1002/anie.200804029
149. Klinman, J. P. (2009). An integrated model for enzyme catalysis emerges from studies of hydrogen tunneling. Chem. Phys. Lett. 471, 179-193. doi: 10.1016/j.cplett.2009.01.038
150. Knapp, M. J., and Klinman, J. P. (2002). Environmentally coupled hydrogen tunneling. Eur. J. Biochem. 269, 3113-3121. doi: 10.1046/j.1432-1033.2002.03022.x
151. Knapp, M. J., Rickert, K., and Klinman, J. P. (2002). Temperature-dependent isotope effects in soybean lipoxygenase-1: correlating hydrogen tunneling with protein dynamics. J. Am. Chem. Soc. 124, 3865-3874. doi: 10.1021/ja012205t
152. Koch, W., and Holthausen, M. C. (2001). A Chemist's Guide to Density Functional Theory, 2nd Edn. New York, NY: Wiley-VCH. doi: 10.1002/3527600043
153. Kohn, W. (1999). Electronic structure of matter-wave functions and density functionals. Rev. Mod. Phys. 71, 1253-1266. doi: 10.1103/RevModPhys.71.1253
154. Kohn, W., Becke, A. D., and Parr, R. G. (1996). Density functional theory of electronic structure. J. Phys. Chem. 100, 12974-12980. doi: 10.1021/jp960669l
155. Kohn, W., and Sham, L. J. (1965). Self-consistent equations including exchange and correlation effects. Phys. Rev. 140, A1133-A1138. doi: 10.1103/PhysRev.140.A1133
156. Krámos, B., and Oláh, J. (2014). Enolization as an alternative proton delivery pathway in human aromatase (P450 19A1). J. Phys. Chem. B 118, 390-405. doi: 10.1021/jp407365x
157. Krámos, B. Z., Menyhárd, D. R. K., and Oláh, J. (2012). Direct hydride shift mechanism and stereoselectivity of P450nor confirmed by QM/MM calculations. J. Phys. Chem. B 116, 872-885. doi: 10.1021/jp2080918
158. Krebs, C., Fujimori, D. G., Walsh, C. T., and Bollinger, J. M. Jr. (2007). Non-heme Fe(IV)-oxo intermediates. Acc. Chem. Res. 40, 484-492. doi: 10.1021/ar700066p
159. Kumar, D., Altun, A., Shaik, S., and Thiel, W. (2011). Water as biocatalyst in cytochrome P450. Faraday Discuss. 148, 373-383. doi: 10.1039/c004950f
160. 2+: an oxidant more powerful than P450? J. Am. Chem. Soc. 127, 8026-8802. doi: 10.1021/ja0512428
161. Kwiecien, R. A., Le Questel, J.-Y., Lebreton, J., Delaforge, M., André, F., Pihan, E., et al. (2012). Cytochrome P450-catalyzed degradation of nicotine: fundamental parameters determining hydroxylation by cytochrome P450 2A6 at the 5'-Carbon or the N-methyl carbon. J. Phys. Chem. B 116, 7827-7840. doi: 10.1021/jp304276v
162. Labinger, J. A., and Bercaw, J. E. (2002). Understanding and exploiting C-H bond activation. Nature 417, 507-514. doi: 10.1038/417507a
163. Lai, W., Chen, H., Cohen, S., and Shaik, S. (2011). Will P450cam hydroxylate or desaturate alkanes? QM and QM/MM studies. J. Phys. Chem. Lett. 2, 2229-2235. doi: 10.1021/jz2007534
164. Lai, W., and Shaik, S. (2011). Can ferric-superoxide act as a potential oxidant in P450cam? QM/MM investigation of hydroxylation, epoxidation, and sulfoxidation. J. Am. Chem. Soc. 133, 5444-5452. doi: 10.1021/ja111376n
165. Lange, S. J., and Que, L. Jr. (1998). Oxygen activating nonheme iron enzymes. Curr. Opin. Chem. Biol. 2, 159-172. doi: 10.1016/S1367-5931(98)80057-4
166. Latifi, R., Tahsini, L., Nam, W., and de Visser, S. P. (2012). Regioselectivity of aliphatic versus aromatic hydroxylation by a nonheme iron(II)-superoxo complex. Phys. Chem. Chem. Phys. 14, 2518-2524. doi: 10.1039/c2cp23352e
167. Lee, Y. M., Bang, S., Kim, Y. M., Cho, J., Hong, S., Nomura, T., et al. (2013). A mononuclear nonheme iron(III)-peroxo complex binding redox-inactive metal ions. Chem. Sci. 4, 3917-3923. doi: 10.1039/c3sc51864g
168. Lee, Y.-M., Hong, S., Morimoto, Y., Shin, W., Fukuzumi, S., and Nam, W. (2010). Dioxygen activation by a non-heme iron(II) complex: formation of an iron(IV)-oxo complex via C-H activation by a putative iron(III)-superoxo species. J. Am. Chem. Soc. 132, 10668-10670. doi: 10.1021/ja103903c
169. Lehnert, N., Neese, F., Ho, R. Y. N., Que, L. Jr., and Solomon, E. I. (2002). Electronic structure and reactivity of low-spin Fe(III)-hydroperoxo complexes: comparison to activated bleomycin. J. Am. Chem. Soc. 124, 10810-10822. doi: 10.1021/ja012621d
170. Levy, M. (1979). Universal variational functionals of electron densities, first-order density matrices, and natural spin-orbitals and solution of the v-representability problem. Proc. Natl. Acad. Sci. U.S.A. 76, 6062-6065. doi: 10.1073/pnas.76.12.6062
171. Li, C., and Shaik, S. (2013). How do perfluorinated alkanoic acids elicit cytochrome P450 to catalyze methane hydroxylation? An MD and QM/MM study. RSC Advances 3, 2995-3005. doi: 10.1039/c2ra22294a
172. Li, C., Zhang, L., Zhang, C., Hirao, H., Wu, W., and Shaik, S. (2007). Which oxidant is really responsible for sulfur oxidation by cytochrome P450? Angew. Chem. Int. Ed. Engl. 46, 8168-8170. doi: 10.1002/anie.200702867
173. Li, D., Huang, X., Lin, J., and Zhan, C.-G. (2013). Catalytic mechanism of cytochrome P450 for N-methylhydroxylation of nicotine: reaction pathways and regioselectivity of the enzymatic nicotine oxidation. Dalton Trans. 42, 3812-3820. doi: 10.1039/c2dt32106h
174. Li, D., Wang, Y., and Han, K. (2012). Recent density functional theory model calculations of drug metabolism by cytochrome P450. Coord. Chem. Rev. 256, 1137-1150. doi: 10.1016/j.ccr.2012.01.016
175. IV=O at a nonheme iron(II) center. Insights into the O-O bond cleavage step. J. Am. Chem. Soc. 132, 2134-2135. doi: 10.1021/ja9101908
176. IV-O complex. J. Am. Chem. Soc. 133, 7256-7259. doi: 10.1021/ja111742z
177. Lian, P., Li, J., Wang, D.-Q., and Wei, D.-Q. (2013). Car-Parrinello molecular dynamics/molecular mechanics (CPMD/MM) simulation study of coupling and uncoupling mechanisms of cytochrome P450cam. J. Phys. Chem. B 117, 7849-7856. doi: 10.1021/jp312107r
178. IV=O complex of a tetradentate tripodal nonheme ligand. Proc. Natl. Acad. Sci. U.S.A. 100, 3665-3670. doi: 10.1073/pnas.0636830100
179. Lin, H., Schöneboom, J. C., Cohen, S., Shaik, S., and Thiel, W. (2004). QM/MM study of the product-enzyme complex in P450cam catalysis. J. Phys. Chem. B 108, 10083-10088. doi: 10.1021/jp0493632
180. Lin, H., and Truhlar, D. G. (2007). QM/MM: what have we learned, where are we, and where do we go from here? Theor. Chem. Acc. 117, 185-199. doi: 10.1007/s00214-006-0143-z
181. Llano, J., and Gauld, J. W. (2010). Mechanistics of enzyme catalysis: From small to large active-site models. Quantum Biochem. 643-666. doi: 10.1002/9783527629213.ch23
182. Lonsdale, R., Harvey, J. N., and Mulholland, A. J. (2010). Inclusion of dispersion effects significantly improves accuracy of calculated reaction barriers for cytochrome P450 catalyzed reactions. J. Phys. Chem. Lett. 1, 3232-3237. doi: 10.1021/jz101279n
183. Lonsdale, R., Harvey, J. N., and Mulholland, A. J. (2012). Effects of dispersion in density functional based quantum mechanical/molecular mechanical calculations on cytochrome P450 catalyzed reactions. J. Chem. Theory Comput. 8, 4637-4645. doi: 10.1021/ct300329h
184. Lonsdale, R., Houghton, K. T., Zurek, J., Bathelt, C. M., Foloppe, N., De Groot, M. J., et al. (2013). Quantum mechanics/molecular mechanics modeling of regioselectivity of drug metabolism in cytochrome P450 2C9. J. Am. Chem. Soc. 135, 8001-8015. doi: 10.1021/ja402016p
185. Lonsdale, R., Oláh, J., Mulholland, A. J., and Harvey, J. N. (2011). Does compound I vary significantly between isoforms of cytochrome P450? J. Am. Chem. Soc. 133, 15464-15474. doi: 10.1021/ja203157u
186. Lundberg, M., and Borowski, T. (2013). Oxoferryl species in mononuclear non-heme iron enzymes: biosynthesis, properties and reactivity from a theoretical perspective. Coord. Chem. Rev. 257, 277-289. doi: 10.1016/j.ccr.2012.03.047
187. Lundberg, M., Kawatsu, T., Vreven, T., Frisch, M. J., and Morokuma, K. (2009). Transition states in a protein environment-ONIOM QM:MM modeling of isopenicillin N synthesis. J. Chem. Theory Comput. 5, 222-234. doi: 10.1021/ct800457g
188. Lynch, B. J., and Truhlar, D. G. (2001). How well can hybrid density functional methods predict transition state geometries and barrier heights? J. Phys. Chem. A 105, 2936-2941. doi: 10.1021/jp004262z
189. Lyons, T. W., and Sanford, M. S. (2010). Palladium-catalyzed ligand-directed C-H functionalization reactions. Chem. Rev. 110, 1147-1169. doi: 10.1021/cr900184e
190. Makris, T. M., von Koenig, K., Schlichting, I., and Sligar, S. G. (2006). The status of high-valent metal oxo complexes in the P450 cytochromes. J. Inorg. Biochem. 100, 507-518. doi: 10.1016/j.jinorgbio.2006.01.025
191. Mas-Ballesté, R., McDonald, A. R., Reed, D., Usharani, D., Schyman, P., Milko, P., et al. (2012). Intramolecular gas-phase reactions of synthetic nonheme oxoiron(IV) ions: proximity and spin-state reactivity rules. Chem. Eur. J. 18, 11747-11760. doi: 10.1002/chem.201200105
192. Maseras, F., and Morokuma, K. (1995). IMOMM: a new integrated ab initio + molecular mechanics geometry optimization scheme of equilibrium structures and transition states. J. Comput. Chem. 16, 1170-1179. doi: 10.1002/jcc.540160911
193. McDonald, A. R., Guo, Y. S., Vu, V., Bominaar, E. L., Munck, E., and Que, L. Jr. (2012). A mononuclear carboxylate-rich oxoiron(IV) complex: a structural and functional mimic of TauD intermediate J. Chem. Sci. 3, 1680-1693. doi: 10.1039/c2sc01044e
194. McDonald, A. R., and Que, L. Jr. (2013). High-valent nonheme iron-oxo complexes: synthesis, structure, and spectroscopy. Coord. Chem. Rev. 257, 414-428. doi: 10.1016/j.ccr.2012.08.002
195. Merkx, M., Kopp, D. A., Sazinsky, M. H., Blazyk, J. L., Müller, J., and Lippard, S. J. (2001). Dioxygen activation and methane hydroxylation by soluble methane monooxygenase: a tale of two irons and three proteins. Angew. Chem. Int. Ed. Engl. 40, 2782-2807. doi: 10.1002/1521-3773(20010803)40:15<2782::AID-ANIE2782>3.0.CO;2-P
196. Meunier, B., de Visser, S. P., and Shaik, S. (2004). Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes. Chem. Rev. 104, 3947-3980. doi: 10.1021/cr020443g
197. Murphy, R. B., Philipp, D. M., and Friesner, R. A. (2000). A mixed quantum mechanics/molecular mechanics (QM/MM) method for large-scale modeling of chemistry in protein environments. J. Comput. Chem. 21, 1442-1457. doi: 10.1002/1096-987X(200012)21:16<1442::AID-JCC3>3.0.CO;2-O
198. 2+) and ligands (porphine, corrin, and TMC). Polyhedron 52, 96-101. doi: 10.1016/j.poly.2012.11.018
199. Nam, K., Gao, J., and York, D. M. (2005). An efficient linear-scaling ewald method for long-range electrostatic interactions in combined QM/MM calculations. J. Chem. Theory Comput. 1, 2-13. doi: 10.1021/ct049941i
200. Nam, W. (2007). High-valent iron(IV)-oxo complexes of heme and non-heme ligands in oxygenation reactions. Acc. Chem. Res. 40, 522-531. doi: 10.1021/ar700027f
201. Nam, W., Lee, Y.-M., and Fukuzumi, S. (2014). Tuning reactivity and mechanism in oxidation reactions by mononuclear nonheme iron(IV)-oxo complexes. Acc. Chem. Res. doi: 10.1021/ar400258p. [Epub ahead of print].
202. Neese, F. (2006). A critical evaluation of DFT, including time-dependent DFT, applied to bioinorganic chemistry. J. Biol. Inorg. Chem. 11, 702-711. doi: 10.1007/s00775-006-0138-1
203. Neese, F. (2009). Prediction of molecular properties and molecular spectroscopy with density functional theory: from fundamental theory to exchange-coupling. Coord. Chem. Rev. 253, 526-563. doi: 10.1016/j.ccr.2008.05.014
204. Neidig, M. L., Decker, A., Choroba, O. W., Huang, F., Kavana, M., Moran, G. R., et al. (2006). Spectroscopic and electronic structure studies of aromatic electrophilic attack and hydrogen-atom abstraction by non-heme iron enzymes. Proc. Natl. Acad. Sci. U.S.A. 103, 12966-12973. doi: 10.1073/pnas.0605067103
205. Newmyer, S. L., and Ortiz de Montellano, P. R. (1995). Horseradish peroxidase His-42→Ala, His-42→Val, and Phe-41→Ala mutants: histidine catalysis and control of substrate access to the heme iron. J. Biol. Chem. 270, 19430-19438.
206. Noack, H., and Siegbahn, P. E. M. (2007). Theoretical investigation on the oxidative chlorination performed by a biomimetic non-heme iron catalyst. J. Biol. Inorg. Chem. 12, 1151-1162. doi: 10.1007/s00775-007-0284-0
207. Ogliaro, F., Cohen, S., de Visser, S. P., and Shaik, S. (2000b). Medium polarization and hydrogen bonding effects on compound I of cytochrome P450: what kind of a radical is it really? J. Am. Chem. Soc. 122, 12892-12893. doi: 10.1021/ja005619f
208. Ogliaro, F., de Visser, S. P., Cohen, S., Sharma, P. K., and Shaik, S. (2002). Searching for the second oxidant in the catalytic cycle of cytochrome P450: a theoretical investigation of the iron(III)-hydroperoxo species and its epoxidation pathways. J. Am. Chem. Soc. 124, 2806-2817. doi: 10.1021/ja0171963
209. Ogliaro, F., Harris, N., Cohen, S., Filatov, M., de Visser, S. P., and Shaik, S. (2000a). A model "rebound" mechanism of hydroxylation by cytochrome P450: stepwise and effectively concerted pathways, and their reactivity patterns. J. Am. Chem. Soc. 122, 8977-8989. doi: 10.1021/ja991878x
210. Olsson, M. H. M., Siegbahn, P. E. M., and Warshel, A. (2004a). Simulating large nuclear quantum mechanical corrections in hydrogen atom transfer reactions in metalloenzymes. J. Biol. Inorg. Chem. 9, 96-99. doi: 10.1007/s00775-003-0503-2
211. Olsson, M. H. M., Siegbahn, P. E. M., and Warshel, A. (2004b). Simulations of the large kinetic isotope effect and the temperature dependence of the hydrogen atom transfer in lipoxygenase. J. Am. Chem. Soc. 126, 2820-2828. doi: 10.1021/ja037233l
212. Orio, M., Pantazis, D. A., and Neese, F. (2009). Density functional theory. Photosynth. Res. 102, 443-453. doi: 10.1007/s11120-009-9404-8
213. Orr, S. T. M., Ripp, S. L., Ballard, T. E., Henderson, J. L., Scott, D. O., Obach, R. S., et al. (2012). Mechanism-based inactivation (MBI) of cytochrome P450 enzymes: structure-activity relationships and discovery strategies to mitigate drug-drug interaction risks. J. Med. Chem. 55, 4896-4933. doi: 10.1021/jm300065h
214. Ortiz de Montellano., P. R. (2005). Cytochrome P450: Structure, Mechanism, and Biochemistry, 3rd Edn. New York, NY: Kluwer Academic/Plenum Publishers. doi: 10.1007/b139087
215. Ortiz de Montellano, P. R. (2010). Hydrocarbon hydroxylation by cytochrome P450 enzymes. Chem. Rev. 110, 932-948. doi: 10.1021/cr9002193
216. Parr, R. G., and Yang, W. (1989). Density-Functional Theory of Atoms and Molecules. New York, NY: Oxford University Press.
217. Peck, S. C., Cooke, H. A., Cicchillo, R. M., Malova, P., Hammerschmidt, F., Nair, S. K., et al. (2011). Mechanism and substrate recognition of 2-hydroxyethylphosphonate dioxygenase. Biochemistry 50, 6598-6605. doi: 10.1021/bi200804r
218. Pelkonen, O., Turpeinen, M., Hakkola, J., Honkakoski, P., Hukkanen, J., and Raunio, H. (2008). Inhibition and induction of human cytochrome P450 enzymes: current status. Arch. Toxicol. 82, 667-715. doi: 10.1007/s00204-008-0332-8
219. Perdew, J. P., Ruzsinszky, A., Constantin, L. A., Sun, J., and Csonka, G. I. (2009). Some fundamental issues in ground-state density functional theory: a guide for the perplexed. J. Chem. Theory Comput. 5, 902-908. doi: 10.1021/ct800531s
220. Perdew, J. P., Ruzsinszky, A., Tao, J., Staroverov, V. N., Scuseria, G. E., and Csonka, G. I. (2005). Prescription for the design and selection of density functional approximations: more constraint satisfaction with fewer fits. J. Chem. Phys. 123, 062201. doi: 10.1063/1.1904565
221. Perdew, J. P., and Schmidt, K. (2001). Jacob's ladder of density functional approximations for the exchange-correlation energy. AIP Conf. Proc. 577, 1-20. doi: 10.1063/1.1390175
222. Phatak, P., Sumner, I., and Iyengar, S. S. (2012). Gauging the flexibility of the active site in soybean lipoxygenase-1 (SLO-1) through an atom-centered density matrix propagation (ADMP) treatment that facilitates the sampling of rare events. J. Phys. Chem. B 116, 10145-10164. doi: 10.1021/jp3015047
223. Porro, C. S., Sutcliffe, M. J., and de Visser, S. P. (2009). Quantum mechanics/molecular mechanics studies on the sulfoxidation of dimethyl sulfide by compound I and compound 0 of cytochrome P450: which is the better oxidant? J. Phys. Chem. A. 113, 11635-11642. doi: 10.1021/jp9023926
224. Poulos, T. L. (2014). Heme enzyme structure and function. Chem. Rev. doi: 10.1021/cr400415k
225. Poulos, T. L., and Kraut, J. (1980). The stereochemistry of peroxidase catalysis. J. Biol. Chem. 255, 8199-8205.
226. Que, L. Jr. (2007). The road to non-heme oxoferryls and beyond. Acc. Chem. Res. 40, 493-500. doi: 10.1021/ar700024g
227. Que, L. Jr., and Ho, R. Y. N. (1996). Dioxygen activation by enzymes with mononuclear non-heme iron active sites. Chem. Rev. 96, 2607-2624. doi: 10.1021/cr960039f
228. Que, L. Jr., and Tolman, W. B. (2008). Biologically inspired oxidation catalysis. Nature 455, 333-340. doi: 10.1038/nature07371
229. Quinonero, D., Morokuma, K., Musaev, D. G., Mas-Ballesté, R., and Que, L. Jr. (2005). Metal-peroxo versus metal-oxo oxidants in non-heme iron-catalyzed olefin oxidations: computational and experimental studies on the effect of water. J. Am. Chem. Soc. 127, 6548-6549. doi: 10.1021/ja051062y
230. Radon, M., and Broclawik, E. (2007). Peculiarities of the electronic structure of cytochrome P450 compound I: CASPT2 and DFT modeling. J. Chem. Theory Comput. 3, 728-734. doi: 10.1021/ct600363a
231. Riccardi, D., Schaefer, P., Yang, Y., Yu, H., Ghosh, N., Prat-Resina, X., et al. (2006). Development of effective quantum mechanical/molecular mechanical (QM/MM) methods for complex biological processes. J. Phys. Chem. B 110, 6458-6469. doi: 10.1021/jp056361o
232. Rittle, J., and Green, M. T. (2010). Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics. Science 330, 933-937. doi: 10.1126/science.1193478
233. Roelfes, G., Vrajmasu, V., Chen, K., Ho, R. Y. N., Rohde, J. U., Zondervan, C., et al. (2003). End-on and side-on peroxo derivatives of non-heme iron complexes with pentadentate ligands: models for putative intermediates in biological iron/dioxygen chemistry. Inorg. Chem. 42, 2639-2653. doi: 10.1021/ic034065p
234. Rohde, J. U., In, J. H., Lim, M. H., Brennessel, W. W., Bukowski, M. R., Stubna, A., et al Jr. (2003). Crystallographic and spectroscopic characterization of a nonheme Fe(IV)=O complex. Science 299, 1037-1039. doi: 10.1126/science.299.5609.1037
235. Rohde, J.-U., Stubna, A., Bominaar, E. L., Münck, E., Nam, W., and Que, L. Jr. (2006). Nonheme oxoiron(IV) complexes of tris(2-pyridylmethyl)amine with cis-monoanionic ligands. Inorg. Chem. 45, 6435-6445. doi: 10.1021/ic060740u
236. Römelt, M., Ye, S., and Neese, F. (2009). Calibration of modern density functional theory methods for the prediction of 57Fe Mössbauer isomer shifts: meta-GGA and double-hybrid functionals. Inorg. Chem. 48, 784-785. doi: 10.1021/ic801535v
237. Ryabov, A. D. (1990). Mechanisms of intramolecular activation of carbon-hydrogen bonds in transition-metal complexes. Chem. Rev. 90, 403-424. doi: 10.1021/cr00100a004
238. Rydberg, P., Jørgensen, F. S., and Olsen, L. (2014). Use of density functional theory in drug metabolism studies. Expert Opin. Drug Metab. Toxicol. 10, 215-227. doi: 10.1517/17425255.2014.864278
239. Rydberg, P., and Olsen, L. (2011). Do two different reaction mechanisms contribute to the hydroxylation of primary amines by cytochrome P450? J. Chem. Theory Comput. 7, 3399-3404. doi: 10.1021/ct200422p
240. Sahu, S., Widger, L. R., Quesne, M. G., de Visser, S. P., Matsumura, H., Moënne-Loccoz, P., et al. (2013). Secondary coordination sphere influence on the reactivity of nonheme iron(II) complexes: an experimental and DFT approach. J. Am. Chem. Soc. 135, 10590-10593. doi: 10.1021/ja402688t
241. Sameera, W. M. C., and Maseras, F. (2012). Transition metal catalysis by density functional theory and density functional theory/molecular mechanics. WIREs Comput. Mol. Sci. 2, 375-385. doi: 10.1002/wcms.1092
242. Sastri, C. V., Lee, J., Oh, K., Yoon, J. L., Jackson, T. A., Ray, K., et al. (2007). Axial ligand tuning of a nonheme iron(IV)-oxo unit for hydrogen atom abstraction. Proc. Natl. Acad. Sci. U.S.A. 104, 19181-19186. doi: 10.1073/pnas.0709471104
243. IV=O complexes: observation of near-UV LMCT bands and Fe=O raman vibrations. J. Am. Chem. Soc. 127, 12494-12495. doi: 10.1021/ja0540573
244. Schlichting, I., Berendzen, J., Chu, K., Stock, A. M., Maves, S. A., Benson, D. E., et al. (2000). The catalytic pathway of cytochrome P450cam at atomic resolution. Science 287, 1615-1622. doi: 10.1126/science.287.5458.1615
245. Schmidt, M. W., Baldridge, K. K., Boatz, J. A., Elbert, S. T., Gordon, M. S., Jensen, J. H., et al. (1993). General atomic and molecular electronic structure system. J. Comput. Chem. 14, 1347-1363. doi: 10.1002/jcc.540141112
246. Schöneboom, J. C., Cohen, S., Lin, H., Shaik, S., and Thiel, W. (2004). Quantum mechanical/molecular mechanical investigation of the mechanism of C-H hydroxylation of camphor by cytochrome P450cam: theory supports a two-state rebound mechanism. J. Am. Chem. Soc. 126, 4017-4034. doi: 10.1021/ja039847w
247. Schöneboom, J. C., Lin, H., Reuter, N., Thiel, W., Cohen, S., Ogliaro, F., et al. (2002). The elusive oxidant species of cytochrome P450 enzymes: characterization by combined quantum mechanical/molecular mechanical (QM/MM) calculations. J. Am. Chem. Soc. 124, 8142-8151. doi: 10.1021/ja026279w
248. Schöneboom, J. C., Neese, F., and Thiel, W. (2005). Toward identification of the compound I reactive intermediate in cytochrome P450 chemistry: a QM/MM study of its EPR and Mössbauer parameters. J. Am. Chem. Soc. 127, 5840-5853. doi: 10.1021/ja0424732
249. Schöneboom, J. C., and Thiel, W. (2004). The resting state of P450cam: a QM/MM study. J. Phys. Chem. B 108, 7468-7478. doi: 10.1021/jp049596t
250. Schröder, D., Shaik, S., and Schwarz, H. (2000). Two-state reactivity as a new concept in organometallic chemistry. Acc. Chem. Res. 33, 139-145. doi: 10.1021/ar990028j
251. Schwarz, H. (2011). Chemistry with methane: concepts rather than recipes. Angew. Chem. Int. Ed. Engl. 50, 10096-10115. doi: 10.1002/anie.201006424
252. Schyman, P., Lai, W. Z., Chen, H., Wang, Y., and Shaik, S. (2011). The directive of the protein: how does cytochrome P450 select the mechanism of dopamine formation? J. Am. Chem. Soc. 133, 7977-7984. doi: 10.1021/ja201665x
253. Senn, H. M., and Thiel, W. (2007a). QM/MM methods for biological systems. Top. Curr. Chem. 268, 173-290. doi: 10.1007/128_2006_084
254. Senn, H. M., and Thiel, W. (2007b). QM/MM studies of enzymes. Curr. Opin. Chem. Biol. 11, 182-187. doi: 10.1016/j.cbpa.2007.01.684
255. Senn, H. M., and Thiel, W. (2009). QM/MM methods for biomolecular systems. Angew. Chem. Int. Ed. Engl. 48, 1198-1229. doi: 10.1002/anie.200802019
256. Seo, M. S., Kim, N. H., Cho, K.-B., So, J. E., Park, S. K., Clémancey, M., et al. (2011). A mononuclear nonheme iron(IV)-oxo complex which is more reactive than cytochrome P450 model compound I. Chem. Sci. 2, 1039-1045. doi: 10.1039/c1sc00062d
257. Seregin, I. V., and Gevorgyan, V. (2007). Direct transition metal-catalyzed functionalization of heteroaromatic compounds. Chem. Soc. Rev. 36, 1173-1193. doi: 10.1039/b606984n
258. Shaik, S., Chen, H., and Janardanan, D. (2011). Exchange-enhanced reactivity in bond activation by metal-oxo enzymes and synthetic reagents. Nat. Chem. 3, 19-27. doi: 10.1038/nchem.943
259. Shaik, S., Cohen, S., Wang, Y., Chen, H., Kumar, D., and Thiel, W. (2010a). P450 enzymes: their structure, reactivity, and selectivity-modeled by QM/MM calculations. Chem. Rev. 110, 949-1017. doi: 10.1021/cr900121s
260. Shaik, S., Filatov, M., Schröder, D., and Schwarz, H. (1998). Electronic structure makes a difference: cytochrome P-450 mediated hydroxylations of hydrocarbons as a two-state reactivity paradigm. Chem. Eur. J. 4, 193-199.
261. Shaik, S., Hirao, H., and Kumar, D. (2007a). Reactivity of high-valent iron-oxo species in enzymes and synthetic reagents: a tale of many states. Acc. Chem. Res. 40, 532-542. doi: 10.1021/ar600042c
262. Shaik, S., Hirao, H., and Kumar, D. (2007b). Reactivity patterns of cytochrome P450 enzymes: multifunctionality of the active species, and the two states-two oxidants conundrum. Nat. Prod. Rep. 24, 533-552. doi: 10.1039/b604192m
263. Shaik, S., Kumar, D., de Visser, S. P., Altun, A., and Thiel, W. (2005). Theoretical perspective on the structure and mechanism of cytochrome P450 enzymes. Chem. Rev. 105, 2279-2328. doi: 10.1021/cr030722j
264. Shaik, S., Lai, W., Chen, H., and Wang, Y. (2010c). The valence bond way: reactivity patterns of cytochrome P450 enzymes and synthetic analogs. Acc. Chem. Res. 43, 1154-1165. doi: 10.1021/ar100038u
265. Shaik, S., Wang, Y., Chen, H., Song, J. S. A., and Meir, R. (2010b). Valence bond modelling and density functional theory calculations of reactivity and mechanism of cytochrome P450 enzymes: thioether sulfoxidation. Faraday Discuss. 145, 49-70. doi: 10.1039/b906094d
266. Shilov, A. E., and Shteinman, A. A. (1999). Oxygen atom transfer into C-H bond in biological and model chemical systems. Mechanistic aspects. Acc. Chem. Res. 32, 763-771. doi: 10.1021/ar980009u
267. Shilov, A. E., and Shul'pin, G. B. (1997). Activation of C-H bonds by metal complexes. Chem. Rev. 97, 2879-2932. doi: 10.1021/cr9411886
268. Shoji, M., Isobe, H., Saito, T., Yabushita, H., Koizumi, K., Kitagawa, Y., et al. (2008). Theory of chemical bonds in metalloenzymes. VII. Hybrid-density functional theory studies on the electronic structures of P450. Int. J. Quantum Chem. 108, 631-650. doi: 10.1002/qua.21547
269. 2 diamond core structure for the key intermediate Q of methane monooxygenase. Science 275, 515-518. doi: 10.1126/science.275.5299.515
270. Sicking, W., Korth, H.-G., Jansen, G., de Groot, H., and Sustmann, R. (2007). Hydrogen peroxide decomposition by a non-heme iron(III) catalase mimic: a DFT study. Chem. Eur. J. 13, 4230-4245. doi: 10.1002/chem.200601209
271. Siegbahn, P. E. M. (2006). The performance of hybrid DFT for mechanisms involving transition metal complexes in enzymes. J. Biol. Inorg. Chem. 11, 695-701. doi: 10.1007/s00775-006-0137-2
272. Siegbahn, P. E. M., and Blomberg, M. R. A. (2010). Quantum chemical studies of proton-coupled electron transfer in metalloenzymes. Chem. Rev. 110, 7040-7061. doi: 10.1021/cr100070p
273. Siegbahn, P. E. M., Blomberg, M. R. A., and Chen, S. L. (2010). Significant van der Waals effects in transition metal complexes. J. Chem. Theory Comput. 6, 2040-2044. doi: 10.1021/ct100213e
274. Siegbahn, P. E. M., and Borowski, T. (2006). Modeling enzymatic reactions involving transition metals. Acc. Chem. Res. 39, 729-738. doi: 10.1021/ar050123u
275. Sligar, S. G., Makris, T. M., and Denisov, I. G. (2005). Thirty years of microbial P450 monooxygenase research: peroxo-heme intermediates-the central bus station in heme oxygenase catalysis. Biochem. Biophys. Res. Commun. 338, 346-354. doi: 10.1016/j.bbrc.2005.08.094
276. Solomon, E. I., Brunold, T. C., Davis, M. I., Kemsley, J. N., Lee, S.-K., Lehnert, N., et al. (2000). Geometric and electronic structure/function correlations in non-heme iron enzymes. Chem. Rev. 100, 235-350. doi: 10.1021/cr9900275
277. Solomon, E. I., Wong, S. D., Liu, L. V., Decker, A., and Chow, M. S. (2009). Peroxo and oxo intermediates in mononuclear nonheme iron enzymes and related active sites. Curr. Opin. Chem. Biol. 13, 99-113. doi: 10.1016/j.cbpa.2009.02.011
278. Sono, M., Roach, M. P., Coulter, E. D., and Dawson, J. H. (1996). Heme-containing oxygenases. Chem. Rev. 96, 2841-2887. doi: 10.1021/cr9500500
279. Stubbe, J., Nocera, D. G., Yee, C. S., and Chang, M. C. (2003). Radical initiation in the class I ribonucleotide reductase: long-range proton-coupled electron transfer? Chem. Rev. 103, 2167-2202. doi: 10.1021/cr020421u
280. Su, P., and Li, H. (2009). Energy decomposition analysis of covalent bonds and intermolecular interactions. J.Chem. Phys. 131, 014102. doi: 10.1063/1.3159673
281. Sun, X., Geng, C., Huo, R., Ryde, U., Bu, Y., and Li, J. (2014). Large equatorial ligand effects on C-H bond activation by nonheme iron(IV)-oxo complexes. J. Phys. Chem. B. 118, 1493-1500. doi: 10.1021/jp410727r
282. 2 oxidative addition. J. Phys. Chem. 100, 19357-19363. doi: 10.1021/jp962071j
283. Swart, M. (2008). Accurate spin-state energies for iron complexes. J. Chem. Theory Comput. 4, 2057-2066. doi: 10.1021/ct800277a
284. Tanaka, M., Ishimori, K., Mukai, M., Kitagawa, T., and Morishima, I. (1997). Catalytic activities and structural properties of horseradish peroxidase distal His42→Glu or Gln mutant. Biochemistry 36, 9889-9898. doi: 10.1021/bi970906q
285. Tang, H., Guan, J., Liu, H., and Huang, X. (2013). Analysis of an alternative to the H-atom abstraction mechanism in methane C-H bond activation by nonheme iron(IV)-oxo oxidants. Dalton Trans. 42, 10260-10270. doi: 10.1039/c3dt50866h
286. Taxak, N., Desai, P. V., Patel, B., Mohutsky, M., Klimkowski, V. J., Gombar, V., et al. (2012). Metabolic-intermediate complex formation with cytochrome P450: theoretical studies in elucidating the reaction pathway for the generation of reactive nitroso intermediate. J. Comput. Chem. 33, 1740-1747. doi: 10.1002/jcc.23008
287. Taxak, N., Kalra, S., and Bharatam, P. V. (2013b). Mechanism-based inactivation of cytochromes by furan epoxide: unraveling the molecular mechanism. Inorg. Chem. 52, 13496-13508. doi: 10.1021/ic401907k
288. Taxak, N., Patel, B., and Bharatam, P. V. (2013a). Carbene generation by cytochromes and electronic structure of heme-iron-porphyrin-carbene complex: a quantum chemical study. Inorg. Chem. 52, 5097-5109. doi: 10.1021/ic400010d
289. Tejero, I., Garcia-Viloca, M., González-Lafont, Á., Lluch, J. M., and York, D. M. (2006). Enzyme dynamics and tunneling enhanced by compression in the hydrogen abstraction catalyzed by soybean lipoxygenase-1. J. Phys. Chem. B 110, 24708-24719. doi: 10.1021/jp066263i
290. Thellamurege, N., and Hirao, H. (2013). Water complexes of cytochrome P450: insights from energy decomposition analysis. Molecules 18, 6782-6791. doi: 10.3390/molecules18066782
291. Thellamurege, N. M., and Hirao, H. (2014). Effect of protein environment within cytochrome P450cam evaluated using a polarizable-embedding QM/MM method. J. Phys. Chem. B 118, 2084-2092. doi: 10.1021/jp412538n
292. Thellamurege, N. M., Si, D., Cui, F., Zhu, H., Lai, R., and Li, H. (2013). QuanPol: a full spectrum and seamless QM/MM program. J. Comput. Chem. 34, 2816-2833. doi: 10.1002/jcc.23435
293. Thibon, A., England, J., Martinho, M., Young, V. G. Jr., Frisch, J. R., Guillot, R., et al. (2008). Proton and reductant-assisted dioxygen activation by a nonheme iron(II) complex to form an oxoiron(IV) intermediate. Angew. Chem. Int. Ed. Engl. 47, 7064-7067. doi: 10.1002/anie.200801832
294. Tian, L., and Friesner, R. A. (2009). QM/MM simulation on P450 BM3 enzyme catalysis mechanism. J. Chem. Theory Comput. 5, 1421-1431. doi: 10.1021/ct900040n
295. Tshuva, E. Y., and Lippard, S. J. (2004). Synthetic models for non-heme carboxylate-bridged diiron metalloproteins: strategies and tactics. Chem. Rev. 104, 987-1012. doi: 10.1021/cr020622y
296. Usharani, D., Janardanan, D., Li, C., and Shaik, S. (2013a). A theory for bioinorganic chemical reactivity of oxometal complexes and analogous oxidants: the exchange and orbital-selection rules. Acc. Chem. Res. 46, 471-482. doi: 10.1021/ar300204y
297. Usharani, D., Lacy, D. C., Borovik, A. S., and Shaik, S. (2013b). Dichotomous hydrogen atom transfer vs proton-coupled electron transfer during activation of X-H bonds (X = C, N, O) by nonheme iron-oxo complexes of variable basicity. J. Am. Chem. Soc. 135, 17090-17104. doi: 10.1021/ja408073m
298. Usharani, D., Zazza, C., Lai, W., Chourasia, M., Waskell, L., and Shaik, S. (2012). A single-site mutation (F429H) converts the enzyme CYP 2B4 into a heme oxygenase: a QM/MM study. J. Am. Chem. Soc. 134, 4053-4056. doi: 10.1021/ja211905e
299. van der Donk, W. A., Krebs, C., and Bollinger, J. M. Jr. (2010). Substrate activation by iron superoxo intermediates. Curr. Opin. Struct. Biol. 20, 673-683. doi: 10.1016/j.sbi.2010.08.005
300. van der Kamp, M. W., and Mulholland, A. J. (2013). Combined quantum mechanics/molecular mechanics (QM/MM) methods in computational enzymology. Biochemistry 52, 2708-2728. doi: 10.1021/bi400215w
301. Van Heuvelen, K. M., Fiedler, A. T., Shan, X., De Hont, R. F., Meier, K. K., Bominaar, E. L., et al. (2012). One-electron oxidation of an oxoiron(IV) complex to form an [O=FeV=NR]+ center. Proc. Natl. Acad. Sci. U.S.A. 109, 11933-11938. doi: 10.1073/pnas.1206457109
302. Vancoillie, S., Zhao, H., Radon, M., and Pierloot, K. (2010). Performance of CASPT2 and DFT for relative spin-state energetics of heme models. J. Chem. Theory Comput. 6, 576-582. doi: 10.1021/ct900567c
303. Vardhaman, A. K., Sastri, C. V., Kumar, D., and de Visser, S. P. (2011). Nonheme ferric hydroperoxo intermediates are efficient oxidants of bromide oxidation. Chem. Commun. 47, 11044-11046. doi: 10.1039/c1cc13775a
304. von Hopffgarten, M., and Frenking, G. (2012). Energy decomposition analysis. WIREs Comput. Mol. Sci. 2, 43-62. doi: 10.1002/wcms.71
305. Vreven, T., Byun, K. S., Komáromi, I., Dapprich, S., Montgomery, J. A., Morokuma, K., et al. (2006). Combining quantum mechanics methods with molecular mechanics methods in ONIOM. J. Chem. Theory Comput. 2, 815-826. doi: 10.1021/ct050289g
306. Wallar, B. J., and Lipscomb, J. D. (1996). Dioxygen activation by enzymes containing binuclear non-heme iron clusters. Chem. Rev. 96, 2625-2657. doi: 10.1021/cr9500489
307. 2) complex as a highly efficient oxidant in sulfoxidation reactions: revival of an underrated oxidant in cytochrome P450. J. Chem. Theory Comput. 9, 2519-2525. doi: 10.1021/ct400190f
308. Wang, C., Chang, W. C., Guo, Y., Huang, H., Peck, S. C., Pandelia, M. E., et al. (2013a). Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase. Science 342, 991-995. doi: 10.1126/science.1240373
309. Wang, Y., Chen, H., Makino, M., Shiro, Y., Nagano, S., Asamizu, S., et al. (2009b). Theoretical and experimental studies of the conversion of chromopyrrolic acid to an antitumor derivative by cytochrome P450 StaP: the catalytic role of water molecules. J. Am. Chem. Soc. 131, 6748-6762. doi: 10.1021/ja9003365
310. Wang, Y., Hirao, H., Chen, H., Onaka, H., Nagano, S., and Shaik, S. (2008). Electron transfer activation of chromopyrrolic acid by cytochrome P450 en route to the formation of an antitumor indolocarbazole derivative: theory supports experiment. J. Am. Chem. Soc. 130, 7170-7171. doi: 10.1021/ja711426y
311. 2 and acetic acid is the cyclic ferric peracetate complex, not a perferryloxo complex. ACS Catal. 3, 1334-1341. doi: 10.1021/cs400134g
312. 2+: does the pentadentate ligand wrapping around the metal center differently lead to the different stability and reactivity? J. Biol. Inorg. Chem. 14, 533-545. doi: 10.1007/s00775-009-0468-x
313. Warshel, A., and Levitt, M. (1976). Theoretical studies of enzymic reactions: dielectric, electrostatic and steric stabilization of reaction of lysozyme. J. Mol. Biol. 103, 227-249. doi: 10.1016/0022-2836(76)90311-9
314. Webb, J. R., Burgess, S. A., Cundari, T. R., and Gunnoe, T. B. (2013). Activation of carbon-hydrogen bonds and dihydrogen by 1, 2-CH-addition across metal-heteroatom bonds. Dalton Trans. 42, 16646-16665. doi: 10.1039/c3dt52164h
315. Whitteck, J. T., Cicchillo, R. M., and van der Donk, W. A. (2009). Hydroperoxylation by hydroxyethylphosphonate dioxygenase. J. Am. Chem. Soc. 131, 16225-16232. doi: 10.1021/ja906238r
316. Whitteck, J. T., Malova, P., Peck, S. C., Cicchillo, R. M., Hammerschmidt, F., and van der Donk, W. A. (2011). On the stereochemistry of 2-hydroxyethylphosphonate dioxygenase. J. Am. Chem. Soc. 133, 4236-4239. doi: 10.1021/ja1113326
317. Wirstam, M., Blomberg, M. R., and Siegbahn, P. E. (1999). Reaction mechanism of compound I formation in heme peroxidases: a density functional theory study. J. Am. Chem. Soc. 121, 10178-10185. doi: 10.1021/ja991997c
318. IV=O S=2 non-heme site in TMG3tren: experimentally calibrated insights into reactivity. Angew. Chem. Int. Ed. Engl. 50, 3215-3218. doi: 10.1002/anie.201007692
319. Xing, G., Diao, Y., Hoffart, L. M., Barr, E. W., Prabhu, K. S., Arner, R. J., et al. (2006). Evidence for C-H cleavage by an iron-superoxide complex in the glycol cleavage reaction catalyzed by myo-inositol oxygenase. Proc. Natl. Acad. Sci. U.S.A. 103, 6130-6135. doi: 10.1073/pnas.0508473103
320. Yamaguchi, K., Yamanaka, S., Isobe, H., Shoji, M., Saito, T., Kitagawa, Y., et al. (2009). Theory of chemical bonds in metalloenzymes XIII: singlet and triplet diradical mechanisms of hydroxylations with iron-oxo species and P450 are revisited. Int. J. Quantum Chem 109, 3723-3744. doi: 10.1002/qua.22348
321. Yamaguchi, J., Yamaguchi, A. D., and Itami, K. (2012). C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals. Angew. Chem. Int. Ed. Engl. 51, 8960-9009. doi: 10.1002/anie.201201666
322. Ye, S., and Neese, F. (2009). Quantum chemical studies of C-H activation reactions by high-valent nonheme iron centers. Curr. Opin. Chem. Biol. 13, 89-98. doi: 10.1016/j.cbpa.2009.02.007
323. Ye, S. F., Geng, C. Y., Shaik, S., and Neese, F. (2013). Electronic structure analysis of multistate reactivity in transition metal catalyzed reactions: the case of C-H bond activation by non-heme iron(IV)-oxo cores. Phys. Chem. Chem. Phys. 15, 8017-8030. doi: 10.1039/c3cp00080j
324. Ye, S. F., and Neese, F. (2011). Nonheme oxo-iron(IV) intermediates form an oxyl radical upon approaching the C-H bond activation transition state. Proc. Natl. Acad. Sci. U.S.A. 108, 1228-1233. doi: 10.1073/pnas.1008411108
325. Yoon, J., Wilson, S. A., Jang, Y. K., Seo, M. S., Nehru, K., Hedman, B., et al. (2009). Reactive intermediates in oxygenation reactions with mononuclear nonheme iron catalysts. Angew. Chem. Int. Ed. Engl. 48, 1257-1260. doi: 10.1002/anie.200802672
326. Yosca, T. H., Rittle, J., Krest, C. M., Onderko, E. L., Silakov, A., Calixto, J. C., et al. (2013). Iron(IV)hydroxide pKa and the role of thiolate ligation in C-H bond activation by cytochrome P450. Science 342, 825-829. doi: 10.1126/science.1244373
327. Yoshizawa, K. (2002). Theoretical study on kinetic isotope effects in the C-H bond activation of alkanes by iron-oxo species. Coord. Chem. Rev. 226, 251-259. doi: 10.1016/S0010-8545(01)00464-7
328. Yoshizawa, K., Kamachi, T., and Shiota, Y. (2001). A theoretical study of the dynamic behavior of alkane hydroxylation by a compound I model of cytochrome P450. J. Am. Chem. Soc. 123, 9806-9816. doi: 10.1021/ja010593t
329. Zhao, Y., González-García, N., and Truhlar, D. G. (2005). Benchmark database of barrier heights for heavy atom transfer, nucleophilic substitution, association, and unimolecular reactions and its use to test theoretical methods. J. Phys. Chem. A 109, 2012-2018. doi: 10.1021/jp045141s
330. Zhao, Y., Lynch, B. J., and Truhlar, D. G. (2004). Development and assessment of a new hybrid density functional model for thermochemical kinetics. J. Phys. Chem. A 108, 2715-2719. doi: 10.1021/jp049908s
331. Zhao, Y., and Truhlar, D. G. (2004). Hybrid meta density functional theory methods for thermochemistry, thermochemical kinetics, and noncovalent interactions: the MPW1B95 and MPWB1K models and comparative assessments for hydrogen bonding and van der Waals interactions. J. Phys. Chem. A 108, 6908-6918. doi: 10.1021/jp048147q
332. Zhao, Y., and Truhlar, D. G. (2008). Density functionals with broad applicability in chemistry. Acc. Chem. Res. 41, 157-167. doi: 10.1021/ar700111a
333. Zheng, J., Wang, D., Thiel, W., and Shaik, S. (2006). QM/MM study of mechanisms for compound I formation in the catalytic cycle of cytochrome P450cam. J. Am. Chem. Soc. 128, 13204-13215. doi: 10.1021/ja063439l
334. Zhou, S. F., Chan, S. Y., Goh, B. C., Chan, E., Duan, W., Huang, M., et al. (2005). Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin. Pharmacokinet. 44, 279-304. doi: 10.2165/00003088-200544030-00005
335. Ziegler, T., and Rauk, A. (1979a). A theoretical study of the ethylene-metal bond in complexes between Cu+, Ag+, Au+, Pt0, or Pt2+ and ethylene, based on the Hartree-Fock-Slater transition-state method. Inorg. Chem. 18, 1558-1565. doi: 10.1021/ic50196a034
336. Ziegler, T., and Rauk, A. (1979b). Carbon monoxide, carbon monosulfide, molecular nitrogen, phosphorus trifluoride, and methyl isocyanide as s donors and p acceptors. A theoretical study by the Hartree-Fock-Slater transition-state method. Inorg. Chem. 18, 1755-1759. doi: 10.1021/ic50197a006