Systematic Derivation and Testing of AMBER Force Field Parameters for Fatty Ethers from Quantum Mechanical Calculations

  • M. Velinova
  • Y. Tsoneva
  • Ph. Shushkov
  • A. Ivanova
  • A. Tadjer
Part of the Progress in Theoretical Chemistry and Physics book series (PTCP, volume 22)


Nontoxic drug delivery systems for efficient trans-membrane transport are central in the successful therapy of a number of diseases. Appropriate building blocks of reversible drug-carrying micelles are water-soluble surfactants, e.g. pentaethylene glycol monododecyl ether (C12E5). The present study aims to derive from first principles calculations and to test molecular mechanics parameters for such ethers to be used in subsequent all-atom simulations of micelle formation. Two monomers and one dimer with two different types of periphery, which are short-chain prototypes of the amphiphilic surfactant C12E5, are used as model systems. The geometry of low-energy conformers is obtained from conformational analysis with a modified OPLS force field and optimized at PBE and MP2 levels, with aug-cc-pVTZ basis sets in vacuum and in implicit solvent. The quantum-chemical calculations provide detailed information on the structural flexibility of the surfactant models and can be used as reference for MD simulations. Weak dependence of the parameters sought on the length of the oligomers and higher sensitivity to the type of periphery is found. Validation of the derived molecular mechanics parameters is carried out through comparison of the density, molecular volume, enthalpy of solvation and vaporization obtained from molecular dynamics simulations (Amber99/NPT/300 K) of diethyl ether to the existing experimental data. The two theoretical approaches yield similar results both at molecular level and as secondary thermodynamic output. Moreover, the derived set of molecular mechanics parameters is consistent with experiment and can be used for extensive molecular dynamics simulations of larger CxEy surfactant assemblies.


Torsion Angle Conformational Analysis Valence Angle Force Field Parameter Ether Fragment 
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The research was supported by Project DO-02-256/2008 of the National Science Fund of Bulgaria with partial funding from Projects DCVP-02-2/2009, DO-02-52/2008 and DO-02-136/2008; the Alexander von Humboldt Foundation is acknowledged for an Equipment Grant.

Supplementary Information Available online are: PBE and MP2 energy data (Table S1); MP2 torsion angles with conformer population in vacuum (Table S2) and in water (Table S3) for the monomers and analogous data for the dimer (Tables S4, S5); the PBE entries of Table 26.5 (Table S6); RESP charges (Table S7); MD trajectories of control parameters (Fig. S1); rotational barrier about Θ2 of the dimer in water (Fig. S2).


  1. 1.
    (a) Tchoukov P, Mileva E, Exerowa D (2003) Langmuir 19:1215; (b) Mileva E, Tchoukov P, Exerowa D (2005) Adv Coll Interf Sci 47:114Google Scholar
  2. 2.
    Balogh J, Pedersen JS (2008) Prog Colloid Polym Sci 135:101Google Scholar
  3. 3.
    (a) Balogh J, Olsson U, Pedersen JS, Dispers J (2006) Sci Technol 27:497; (b) Balogh J, Olsson U, Dispers J (2007) Sci Technol 28:223; (c)Balogh J, Kaper H, Olsson U, Wennerstrm H (2006) Phys Rev E 73:041506Google Scholar
  4. 4.
    Glass JE, Ed. (1996) Hydrophilic Polymers: Performance with Environmental Acceptability, American Chemical Society, Washington, D.C., Vol. 248Google Scholar
  5. 5.
    (a) Smith GD, Yoon DY, Jaffe RL (1993) Macromolecules 26:5213; (b) Smith GD, Jaffe RL, Yoon DY (1996) J Phys Chem 100:13439Google Scholar
  6. 6.
    Smith GD, Yoon DY, Jaffe RL, Colby RH, Krishnamoorti R, Fetters LJ (1996) Macromolecules 29:3462CrossRefGoogle Scholar
  7. 7.
    Neyertz S, Brown D, Thomas JO (1994) J Chem Phys 101:10064CrossRefGoogle Scholar
  8. 8.
    Lin B, Boinske PT, Halley JW (1996) J Chem Phys 105:1668CrossRefGoogle Scholar
  9. 9.
    Bedrov D, Pekny M, Smith GD (1998) J Phys Chem B 102:996CrossRefGoogle Scholar
  10. 10.
    Smith GD, Borodin O, Bedrov D (2002) J Comput Chem 23:1480CrossRefGoogle Scholar
  11. 11.
    Bedrov D, Smith GD (1999) J Phys Chem B 103:3791CrossRefGoogle Scholar
  12. 12.
    Smith GD, Bedrov D (2002) Macromolecules 35:5712CrossRefGoogle Scholar
  13. 13.
    (a) Jorgensen WL, Tirado-Rives J (1988) J Am Chem Soc 110:1657; (b) Pranate J, Wierschke S, Jorgensen WL (1991) J Am Chem Soc 113:2810Google Scholar
  14. 14.
    Jorgensen WL, Madura JD (1985) Mol Phys 56:1381CrossRefGoogle Scholar
  15. 15.
    Jorgensen WL, Madura JD (1985) Mol Phys 56:1381CrossRefGoogle Scholar
  16. 16.
    (a) Perdew JP, Burke K, Ernzerhof M (1996) Phys Rev Lett 77:3865; (b) Perdew P, Burke K, Ernzerhof M (1997) Phys Rev Lett 78:1396Google Scholar
  17. 17.
    Moller C, Plesset M (1934) Phys Rev 46:618CrossRefGoogle Scholar
  18. 18.
    Kendall RA, Dunning TH Jr, Harrison RJ (1992) J Chem Phys 96:6796CrossRefGoogle Scholar
  19. 19.
    Miertus S, Scrocco E, Tomasi J (1981) J Chem Phys 55:117Google Scholar
  20. 20.
    (a) Bayly CI, Cieplak P, Cornell WD, Kollman PA (1993) J Phys Chem 97:10269; (b) Cieplak P, Cornell WD, Bayly C, Kollman PA (1995) J Comput Chem 16:1357Google Scholar
  21. 21.
    Cornell WD, Cieplak P, Baily CI, Gould IR, Merz KM Jr, Ferguson DC, Fox T, Caldwell JW, Kollman PA (1995) J Am Chem Soc 117:5179CrossRefGoogle Scholar
  22. 22.
    Berendsen JC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) J Chem Phys 81:3684CrossRefGoogle Scholar
  23. 23.
    Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) J Chem Phys 103:8577CrossRefGoogle Scholar
  24. 24.
    HyperChem 7.0 (2002) Hypercube: Gainesville, FLGoogle Scholar
  25. 25.
    Frisch MJ et al (2009) Gaussian, Inc., Wallingford, CTGoogle Scholar
  26. 26.
    Case DA et al (2004) AMBER 8; University of California, San Francisco, CAGoogle Scholar
  27. 27.
    Snyder RG, Zerbi G (1967) Spectrochim Acta 23:391CrossRefGoogle Scholar
  28. 28.
    Wieser H, Laidlaw WG, Krueger PJ, Fuhrer H (1968) Spectrochim Acta 24:1055CrossRefGoogle Scholar
  29. 29.
    Perchard JP, Monier JC, Dixabo P (1971) Spectrochim Acta 27:447CrossRefGoogle Scholar
  30. 30.
    Maissara M, Labenne JP, Devaure J (1985) J Chem Phys 82:451Google Scholar
  31. 31.
    Kanesaka I, Snyder RG, Strauss HL (1986) J Chem Phys 84:395CrossRefGoogle Scholar
  32. 32.
    Kuze N, Kuroki N, Takeuchi H, Egawa T, Konaka S (1993) J Mol Struct 301:81CrossRefGoogle Scholar
  33. 33.
    Astrup EE (1979) Acta Chim Scand A 33:655CrossRefGoogle Scholar
  34. 34.
    Yoshida H, Tanaka T, Matsuura H (1996) Chem Lett 8:637CrossRefGoogle Scholar
  35. 35.
    Goutev N, Ohno K, Matsuura H (2000) J Phys Chem A 104:9226CrossRefGoogle Scholar
  36. 36.
    Yoshida H, Kaneko I, Matsuura H, Ogawa Y, Tasumi M (1992) Chem Phys Lett 196:601CrossRefGoogle Scholar
  37. 37.
    Bedrov D, Borodin O, Smith GD (1998) J Phys Chem B 102:5683CrossRefGoogle Scholar
  38. 38.
    Bedrov D, Smith GD (1998) J Chem Phys 109:8118CrossRefGoogle Scholar
  39. 39.
    Ganguly B, Fuchs B (2000) J Org Chem 65:558CrossRefGoogle Scholar
  40. 40.
    Andersson M, KarlstrBm G (1985) J Phys Chem 89:4967CrossRefGoogle Scholar
  41. 41.
    Inomata K, Abe A (1992) J Phys Chem 96:7934CrossRefGoogle Scholar
  42. 42.
    Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM Jr, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA (1995) J Am Chem Soc 117:5179CrossRefGoogle Scholar
  43. 43.
    Kuchitsu K (1998) Structure of free polyatomic molecules basic data; Springer, Berlin.
  44. 44.
    (a) Favero LB, Caminati W, Velino B (2003) Phys Chem Chem Phys 5:4776; (b) Niidea Y, Hayashi M (2004) J Mol Spectrosc 223:152Google Scholar
  45. 45.
    Maikut OM, Makitra RG, Ya Palchikova E (2006) Russ J Gen Chem 76:170Google Scholar
  46. 46.
    (a) Hansen KC, Rock RS, Larsen RW, Chan SI (2000) J Am Chem Soc 122:11567; (b) Larsen RW, Langley T (1999) J Am Chem Soc 121:4495Google Scholar
  47. 47.
    Dai J, Li X, Zhao L, Sun H (2010) Fluid Phase Equilibria 289:156CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • M. Velinova
    • 1
  • Y. Tsoneva
    • 1
  • Ph. Shushkov
    • 1
  • A. Ivanova
    • 1
  • A. Tadjer
    • 1
  1. 1.Faculty of ChemistryUniversity of SofiaSofiaBulgaria

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