Theoretical study of cyclohexane hydroxylation by three possible isomers of [FeIV(O)(R-TPEN)]2+: does the pentadentate ligand wrapping around the metal center differently lead to the different stability and reactivity?

  • Yi Wang
  • Yong Wang
  • Keli HanEmail author
Original Paper


Density functional theory calculations have been carried out to elucidate the mechanism of cyclohexane hydroxylation by three possible isomers of [FeIV(O)(N-R-N,N′,N′-tris(2-pyridylmethyl)ethane-1,2-diamine)]2+ (R is methyl or benzyl) (Klinker et al. in Angew Chem Int Ed 44:3690–3694, 2005). The calculations offer a mechanistic view and reveal the following features: (a) all the three isomers possess triplet ground states and low-lying quintet excited states, (b) the relative stability follows the order isomer A > isomer B > isomer C, in agreement with the conclusions of Klinker et al., (c) the theoretical investigations provide a rationale to explain the interconversion of the three isomers, (d) the reaction pathways of the C–H hydroxylation are initiated by a hydrogen-abstraction step, and (e) the three isomers react with cyclohexane via two-state-reactivity patterns on competing triplet and quintet spin-state surfaces. As such, in the gas phase, the relative reactivity exhibits the trend isomer B > isomer A, while at the highest level, B2//B1 with zero point energy and solvation corrections, the relative reactivity follows the order isomer B > isomer A > isomer C. Thus, the calculated reaction pathway shows that pyridine rings perpendicular to the Fe–O axis result in more reactive species, and a pyridine ring coordinated trans to the oxygen atom leads to the least reactive isomer.


Non-heme Hydroxylation Density functional calculations 



This work was supported by NKBRSF(2007CB815202) and NSFC(20833008). Our deep appreciation goes to Sason Shaik and Hirao Hajime of the Jerusalem group for their generous help and to Edward I. Solomon and D. Wong Shaun of Stanford University for their useful advice.

Supplementary material

775_2009_468_MOESM1_ESM.pdf (385 kb)
Supplementary material 1 (PDF 385 kb)


  1. 1.
    Que L Jr, Ho RYN (1996) Chem Rev 96:2607–2624PubMedCrossRefGoogle Scholar
  2. 2.
    Solomon EI, Brunold TC, Davis M, Kemsley JN, Lee S-K, Lehnert N, Neese F, Skulan AJ, Yang Y-S, Zhou J (2000) Chem Rev 100:235–350PubMedCrossRefGoogle Scholar
  3. 3.
    Costas M, Mehn MP, Jensen MP, Que L Jr (2004) Chem Rev 104:939–986PubMedCrossRefGoogle Scholar
  4. 4.
    Price JC, Barr EW, Glass TE, Krebs C, Bollinger JM Jr (2003) J Am Chem Soc 125:13008–13009PubMedCrossRefGoogle Scholar
  5. 5.
    Price JC, Barr EW, Tirupati B, Bollinger JM Jr, Krebs C (2003) Biochemistry 42:7497–7508PubMedCrossRefGoogle Scholar
  6. 6.
    Proshlyakov DA, Henshaw TF, Monterosso GR, Ryle MJ, Hausinger RP (2004) J Am Chem Soc 126:1022–1023PubMedCrossRefGoogle Scholar
  7. 7.
    Hoffart LM, Barr EW, Guyer RB, Bollinger JM Jr, Krebs C (2006) Proc Natl Acad Sci USA 103:14738–14743PubMedCrossRefGoogle Scholar
  8. 8.
    Galonic DP, Barr EW, Walsh CT, Bollinger JM Jr, Krebs C (2007) Nat Chem Biol 3:113–116PubMedCrossRefGoogle Scholar
  9. 9.
    Shan XP, Que L Jr (2006) J Inorg Biochem 100:421–433PubMedCrossRefGoogle Scholar
  10. 10.
    Neese F (2006) J Inorg Biochem 100:716–726PubMedCrossRefGoogle Scholar
  11. 11.
    Rohde J-U, In J-H, Lim MH, Brennessel WW, Bukowski MR, Stubna A, Münck E, Nam W, Que L Jr (2003) Science 299:1037–1039PubMedCrossRefGoogle Scholar
  12. 12.
    Lim MH, Rohde J-U, Stubna A, Bukoeski MR, Costas M, Ho RYN, Münck E, Nam W, Que L Jr (2003) Proc Natl Acad Sci USA 100:3665–3670PubMedCrossRefGoogle Scholar
  13. 13.
    Kaizer J, Klinker EJ, Oh NY, Rohde J-U, Song WJ, Stubna A, Kim J, Münck E, Nam W, Que L Jr (2004) J Am Chem Soc 126:472–473PubMedCrossRefGoogle Scholar
  14. 14.
    Kim SO, Sastri CV, Seo MS, Kim J, Nam W (2005) J Am Chem Soc 127:4178–4179PubMedCrossRefGoogle Scholar
  15. 15.
    Oh NY, Suh Y, Park MJ, Seo MS, Kim J, Nam W (2005) Angew Chem Int Ed 44:4235–4239CrossRefGoogle Scholar
  16. 16.
    Sastri CV, Park MJ, Ohta T, Jackson TA, Stubna A, Seo MS, Lee J, Kim J, Kitagawa T, Münck E, Que L Jr, Nam W (2005) J Am Chem Soc 127:12494–12495PubMedCrossRefGoogle Scholar
  17. 17.
    Bukowski MR, Koehntop KD, Stubna A, Bominaar EL, Halfen JA, Münck E, Nam W, Que L Jr (2005) Science 310:1000–1002PubMedCrossRefGoogle Scholar
  18. 18.
    Klinker EJ, Kaizer J, Brennessel WW, Woodrum NL, Cramer CJ, Que L Jr (2005) Angew Chem Int Ed 44:3690–3694CrossRefGoogle Scholar
  19. 19.
    Sastri CV, Oh K, Lee YJ, Seo MS, Shin W, Nam W (2006) Angew Chem Int Ed 45:3992–3995CrossRefGoogle Scholar
  20. 20.
    Krebs C, Fujimori DG, Walsh C, Bollinger JM Jr (2007) Acc Chem Res 40:484–492PubMedCrossRefGoogle Scholar
  21. 21.
    Que L Jr (2007) Acc Chem Res 40:493–500PubMedCrossRefGoogle Scholar
  22. 22.
    Decker A, Clay MD, Solomon EI (2006) J Inorg Biochem 100:697–706PubMedCrossRefGoogle Scholar
  23. 23.
    Neidig ML, Decker A, Choroba OW, Huang FL, Kavana M, Moran GR, Spencer JB, Solomon EI (2006) Proc Natl Acad Sci USA 103:12966–12973PubMedCrossRefGoogle Scholar
  24. 24.
    Decker A, Rohde J-U, Que L Jr, Solomon EI (2004) J Am Chem Soc 126:5378–5379PubMedCrossRefGoogle Scholar
  25. 25.
    Pau MYM, Davis MI, Orville AM, Lipscomb JD, Solomon EI (2007) J Am Chem Soc 129:1944–1958PubMedCrossRefGoogle Scholar
  26. 26.
    Schenk G, Pau MYM, Solomon EI (2004) J Am Chem Soc 126:505–515PubMedCrossRefGoogle Scholar
  27. 27.
    Decker A, Solomon EI (2005) Angew Chem Int Ed 44:2252–2255CrossRefGoogle Scholar
  28. 28.
    Decker A, Rohde J-U, Klinker EJ, Wong SD, Que L Jr, Solomon EI (2007) J Am Chem Soc 129:15983–15996PubMedCrossRefGoogle Scholar
  29. 29.
    Decker A, Solomon EI (2005) Curr Opin Chem Biol 9:152–163PubMedCrossRefGoogle Scholar
  30. 30.
    Shaik S, Hirao H, Kumar D (2007) Acc Chem Res 40:532–542PubMedCrossRefGoogle Scholar
  31. 31.
    Johansson AJ, Blomberg MRA, Siegbahn PEM (2007) J Phys Chem C 111:12397–12406CrossRefGoogle Scholar
  32. 32.
    Hirao H, Que L Jr, Nam W, Shaik S (2008) Chem Eur J 14:1740–1756CrossRefGoogle Scholar
  33. 33.
    Hirao H, Kumar D, Que L Jr, Shaik S (2006) J Am Chem Soc 128:8590–8606PubMedCrossRefGoogle Scholar
  34. 34.
    Kumar D, Hirao H, Que L Jr, Shaik S (2005) J Am Chem Soc 127:8026–8027PubMedCrossRefGoogle Scholar
  35. 35.
    Hirao H, Chen H, Carvajal MA, Wang Y, Shaik S (2008) J Am Chem Soc 130:3319–3327PubMedCrossRefGoogle Scholar
  36. 36.
    de Visser SP, Oh K, Han A-R, Nam W (2007) Inorg Chem 46:4632–4641PubMedCrossRefGoogle Scholar
  37. 37.
    de Visser SP (2006) J Am Chem Soc 128:9813–9824PubMedCrossRefGoogle Scholar
  38. 38.
    de Visser SP (2006) J Am Chem Soc 128:15809–15818PubMedCrossRefGoogle Scholar
  39. 39.
    Balland V, Charlot A-F, Banse F, Girerd J-J, Mattioli TA, Bill E, Bartoli J-F, Battioni P, Mansuy D (2004) Eur J Inorg Chem 2:301–308CrossRefGoogle Scholar
  40. 40.
    Martinho M, Banse F, Bartoli M-F, Mattioli TA, Battioni P, Horner O, Bourcier S, Girerd J-J (2005) Inorg Chem 44:9592–9596PubMedCrossRefGoogle Scholar
  41. 41.
    Paine TK, Costas M, Kaizer J, Que L Jr (2006) J Biol Inorg Chem 11:272–276PubMedCrossRefGoogle Scholar
  42. 42.
    Sastri CV, Seo MS, Park MJ, Kim KM, Nam W (2005) Chem Commun 1405–1407Google Scholar
  43. 43.
    You M, Seo MS, Kim KM, Nam W, Kim J (2006) Bull Korean Chem Soc 27:1140–1144CrossRefGoogle Scholar
  44. 44.
    Sastri CV, Lee J, Oh K, Lee YJ, Lee J, Jackson TA, Ray K, Hirao H, Shin W, Halfen JA, Kim J, Que L Jr, Shaik S, Nam W (2007) Proc Natl Acad Sci USA 104:19181–19186PubMedCrossRefGoogle Scholar
  45. 45.
    Rohde J-U, Que L Jr (2005) Angew Chem Int Ed 44:2255–2258CrossRefGoogle Scholar
  46. 46.
    Nam W (2007) Acc Chem Res 40:522–531PubMedCrossRefGoogle Scholar
  47. 47.
    Rohde J-U, Torelli S, Shan XP, Lim MH, Klinker EJ, Kaizer J, Chen K, Nam W, Que L Jr (2004) J Am Chem Soc 126:16750–16761PubMedCrossRefGoogle Scholar
  48. 48.
    Park MJ, Lee J, Suh Y, Kim J, Nam W (2006) J Am Chem Soc 128:2630–2634PubMedCrossRefGoogle Scholar
  49. 49.
    Nesheim JC, Lipscomb JD (1996) Biochemistry 35:10240–10247PubMedCrossRefGoogle Scholar
  50. 50.
    Frisch MJ et al (2004) Gaussian 03, revision C.02. Gaussian, WallingfordGoogle Scholar
  51. 51.
    Becke AD (1993) J Chem Phys 98:5648–5652CrossRefGoogle Scholar
  52. 52.
    Lee C, Yang W, Parr RG (1988) Phys Rev B 37:785–789CrossRefGoogle Scholar
  53. 53.
    Becke AD (1992) J Chem Phys 96:2155–2160CrossRefGoogle Scholar
  54. 54.
    Becke AD (1992) J Chem Phys 97:9173–9177CrossRefGoogle Scholar
  55. 55.
    Hay JP, Wadt WR (1985) J Chem Phys 82:299–310CrossRefGoogle Scholar
  56. 56.
    Friesner RA, Murphy RB, Beachy MD, Ringlanda MN, Pollard WT, Dunietz BD, Cao YX (1999) J Phys Chem A 103:1913–1928CrossRefGoogle Scholar
  57. 57.
    Melander L, Saunders WH Jr (1987) In: Reaction rates of isotopic molecules. Krieger, Malabar, chap 2Google Scholar
  58. 58.
    Kumar S, de Visser SP, Sharma PK, Cohen S, Shaik S (2004) J Am Chem Soc 126:1907–1920PubMedCrossRefGoogle Scholar
  59. 59.
    de Visser SP (2006) J Biol Inorg Chem 11:168–178PubMedCrossRefGoogle Scholar
  60. 60.
    Bassan A, Blomberg MRA, Siegbahn PEM (2003) Chem Eur J 9:4055–4067CrossRefGoogle Scholar
  61. 61.
    Quinonero D, Morokuma K, Musaev DG, Mas-Balleste R, Que L Jr (2005) J Am Chem Soc 127:6548–6549PubMedCrossRefGoogle Scholar
  62. 62.
    Handy NC, Cohen AJ (2001) Mol Phys 99:403–412CrossRefGoogle Scholar
  63. 63.
    Perdew JP, Burke K, Ernzerhof M (1996) Phys Rev Lett 77:3865–3868PubMedCrossRefGoogle Scholar
  64. 64.
    Perdew JP, Burke K, Ernzerhof M (1997) Phys Rev Lett 78:1396–1396CrossRefGoogle Scholar
  65. 65.
    Swart M, Ehlers AW, Lammertsma K (2004) Mol Phys 102:2467–2474CrossRefGoogle Scholar
  66. 66.
    Groenhof AR, Swart M, Ehlers AW, Lammertsma K (2005) J Phys Chem A 109:3411–3417PubMedCrossRefGoogle Scholar
  67. 67.
    Baker J, Pulay P (2002) J Chem Phys 117:1441–1449CrossRefGoogle Scholar
  68. 68.
    Shaik S, Danovich D, Fiedler A, SchrÖder D, Schwarz H (1995) Helv Chem Acta 78:1393–1407CrossRefGoogle Scholar
  69. 69.
    SchrÖder D, Shaik S, Schwarz H (2000) Acc Chem Res 33:139–145PubMedCrossRefGoogle Scholar
  70. 70.
    Hirao H, Kumar D, Thiel W, Shaik S (2005) J Am Chem Soc 127:13007–13018PubMedCrossRefGoogle Scholar
  71. 71.
    Mola J, Romero I, Rodríguez M, Bozoglian F, Poater A, Solà M, Parella T, Benet-Buchholz J, Fontrodona X, Llobet A (2007) Inorg Chem 46:10707–10716PubMedCrossRefGoogle Scholar
  72. 72.
    Carter EA, Goddard WAIII (1988) J Phys Chem 92:5679–5683CrossRefGoogle Scholar
  73. 73.
    Scott AP, Radom L (1996) J Phys Chem 100:16502–16513CrossRefGoogle Scholar

Copyright information

© SBIC 2009

Authors and Affiliations

  1. 1.State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalianPeople’s Republic of China

Personalised recommendations