Journal of Molecular Modeling

, Volume 18, Issue 8, pp 3455–3466 | Cite as

A test of improved force field parameters for urea: molecular-dynamics simulations of urea crystals

  • Gül Altınbaş Özpınar
  • Frank R. Beierlein
  • Wolfgang Peukert
  • Dirk Zahn
  • Timothy Clark
Original Paper


Molecular-dynamics (MD) simulations of urea crystals of different shapes (cubic, rectangular prismatic, and sheet) have been performed using our previously published force field for urea. This force field has been validated by calculating values for the cohesive energy, sublimation temperature, and melting point from the MD data. The cohesive energies computed from simulations of cubic and rectangular prismatic urea crystals in vacuo at 300 K agreed very well with the experimental sublimation enthalpies reported at 298 K. We also found very good agreement between the melting points as observed experimentally and from simulations. Annealing the crystals just below the melting point leads to reconstruction to form crystal faces that are consistent with experimental observations. The simulations reveal a melting mechanism that involves surface (corner/edge) melting well below the melting point, and rotational disordering of the urea molecules in the corner/edge regions of the crystal, which then facilitates the translational motion of these molecules.


Crystal simulations Force field Molecular dynamics Urea 



This work was supported by the Deutsche Forschungsgemeinschaft as part of the project PE 42710-2 and the Excellence Cluster Engineering of Advanced Materials.

Supplementary material

894_2011_1336_MOESM1_ESM.doc (7 mb)
ESM 1 (DOC 7204 kb)


  1. 1.
    Bonin M, Marshall WG, Weber HP, Tolendo P (1999) Polymorphism in urea. IOP Publishing ISIS. Accessed August 1999.
  2. 2.
    Mathews CK, van Holde KE (1996) Biochemistry, 2nd edn. Cummings, Menlo Park, CA, p 4Google Scholar
  3. 3.
    Bhatnagar VM (1968) Clathrates of urea and thiourea. J Struct Chem 8:513–529. doi: 10.1007/BF00751656 CrossRefGoogle Scholar
  4. 4.
    Theophanides T, Harvey PD (1987) Structural and spectroscopic properties of metal-urea complexes. Coord Chem Rev 76:237–264. doi: 10.1016/0010-8545(87)85005-1 CrossRefGoogle Scholar
  5. 5.
    Boek ES, Briels WJ (1993) Molecular dynamics simulations of aqueous urea solutions: Study of dimer stability and solution structure, and calculation of the total nitrogen radial distribution function GN(r). J Chem Phys 98:1422–1427. doi: 10.1063/1.464306 CrossRefGoogle Scholar
  6. 6.
    Boek ES, Briels WJ, van Eerden J, Feil D (1992) Molecular-dynamics simulations of interfaces between water and crystalline urea. J Chem Phys 96:7010–7018. doi: 10.1063/1.462560 CrossRefGoogle Scholar
  7. 7.
    Åstrand PO, Wallqvist A, Karlström G (1994) Molecular dynamics simulations of 2M aqueous urea solutions. J Phys Chem 98:8224–8233. doi: 10.1021/j100084a046 CrossRefGoogle Scholar
  8. 8.
    Åstrand PO, Wallqvist A, Karlström G (1994) Nonempirical intermolecular potentials for urea – water systems. J Chem Phys 100:1262–1273. doi: 10.1063/1.466655 CrossRefGoogle Scholar
  9. 9.
    Cristinziao P, Lelj F, Amodeo P, Barone V (1987) A molecular dynamics study of associations in solution. An NPT simulation of the urea dimer in water. Chem Phys Lett 140:401–405. doi: 10.1016/0009-2614(87)80755-8 CrossRefGoogle Scholar
  10. 10.
    Hermans J, Berendsen HJC, van Gunsteren WF, Postma JPM (1984) A consistent empirical potential for water–protein interactions. Biopolymers 23:1513–1518. doi: 10.1002/bip.360230807 CrossRefGoogle Scholar
  11. 11.
    Hagler AT, Huler E, Lifson S (1976) Energy functions for peptides and proteins. I. Derivation of a consistent force field including the hydrogen bond from amide crystals. J Am Chem Soc 96:5319–5327. doi: 10.1021/ja00824a004 CrossRefGoogle Scholar
  12. 12.
    Kallies B (2002) Coupling of solvent and solute dynamics—molecular dynamics simulations of aqueous urea solutions with different intramolecular potentials. Phys Chem Chem Phys 4:86–95. doi: 10.1039/b105836n CrossRefGoogle Scholar
  13. 13.
    Caballo-Herrera A, Nilsson L (2006) Urea parameterization for molecular dynamics simulations. J Mol Struct THEOCHEM 758:139–148. doi: 10.1016/j.theochem.2005.10.018 CrossRefGoogle Scholar
  14. 14.
    Özpınar GA, Peukert W, Clark T (2010) An improved generalized AMBER force field (GAFF) for urea. J Mol Mod 16:1427–1440. doi: 10.1007/s00894-010-0650-7 CrossRefGoogle Scholar
  15. 15.
    Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25:1157–1174. doi: 10.1002/jcc.20035 CrossRefGoogle Scholar
  16. 16.
    Moller C, Plesset MS (1934) Note on an Approximation Treatment for Many-Electron Systems. Phys Rev 46:618–622. doi: 10.1103/PhysRev.46.618 CrossRefGoogle Scholar
  17. 17.
    Dunning TH Jr (1989) Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen. J Chem Phys 90:1007–1023. doi: 10.1063/1.456153 CrossRefGoogle Scholar
  18. 18.
    Bayly CI, Cieplak P, Cornell WD, Kollman PA (1993) A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model. J Phys Chem 97:10269–10280. doi: 10.1021/j100142a004 CrossRefGoogle Scholar
  19. 19.
    Zavodnik V, Stash A, Tsirelson V, De Vires R, Feil D (1999) Electron density study of urea using TDS-corrected X-ray diffraction data: quantitative comparison of experimental and theoretical results. Acta Cryst B55:45–54. doi: 10.1107/S0108768198005746 Google Scholar
  20. 20.
    Vaughan P, Donohue J (1952) The structure of urea. Interatomic distances and resonance in urea and related compounds. Acta Cryst 5:530–535. doi: 10.1107/S0365110X52001477 CrossRefGoogle Scholar
  21. 21.
    Worsham JE, Levy HA, Peterson SE (1957) The positions of hydrogen atoms in urea by neutron diffraction. Acta Cryst 10:319–323. doi: 10.1107/S0365110X57000924 CrossRefGoogle Scholar
  22. 22.
    Materials Studio 5.0 (2009), Accelrys Software Inc., San Diego, CA.Google Scholar
  23. 23.
    Case DA, Darden TA, Cheatham TE III, Simmerling CL, Wang J, Duke RE, Luo R, Crowley M, Walker RC, Zhang W, Merz KM, Wang B, Hayik S, Roitberg A, Seabra G, Kolossváry I, Wong KF, Paesani F, Vanicek J, Wu X, Brozell SR, Steinbrecher T, Gohlke H, Yang L, Tan C, Mongan J, Hornak V, Cui G, Mathews DH, Seetin MG, Sagui C, Babin V, Kollman PA (2008) AMBER 10. University of California, San FranciscoGoogle Scholar
  24. 24.
    Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995)A smooth particle mesh Ewald method. J Chem Phys 103:8577-8593. doi: 10.1063/1.470117 Google Scholar
  25. 25.
    Darden T, York D, Pedersen L (1993) Particle mesh Ewald: An N log(N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092. doi: 10.1063/1.464397 CrossRefGoogle Scholar
  26. 26.
    Civalleri B, Doll K, Zicovich-Wilson CM (2007) Ab initio investigation of structure and cohesive energy of crystalline urea. J Phys Chem B 111:26–33. doi: 10.1021/jp065757c CrossRefGoogle Scholar
  27. 27.
    Civalleri B, Zicovich-Wilson CM, Valenzano L, Ugliengo P (2008) B3LYP augmented with an empirical dispersion term (B3LYP-D*) as applied to molecular crystals. Cryst Eng Comm 10:405–410. doi: 10.1039/B715018K Google Scholar
  28. 28.
    Case DA, Darden TA, Cheatham TE III, Simmerling CL, Wang J, Duke RE, Luo R, Merz KM, Pearlman DA, Crowley M, Walker RC, Zhang W, Wang B, Hayik S, Roitberg A, Seabra G, Wong KF, Paesani F, Wu X, Brozell S, Tsui V, Gohlke H, Yang L, Tan C, Mongan J, Hornak V, Cui G, Beroza P, Mathews DH, Schafmeister C, Ross WS, Kollman PA (2006) AMBER 9. University of California, San FranciscoGoogle Scholar
  29. 29.
    Turzi SS (2011) On the Cartesian definition of orientational order parameters. J Math Phys 52:053517CrossRefGoogle Scholar
  30. 30.
    Suzuki K, Onishi S, Koide T, Seki S (1956) Vapor pressures of molecular crystals. XI Vapor pressures of crystalline urea and diformylhydrazine. Energies of hydrogen bonds in these crystals. Bull Chem Soc Jpn 29:127–131. doi: 10.1246/bcsj.29.127 CrossRefGoogle Scholar
  31. 31.
    Ferro D, Barone G, Della Gatta G, Piacente V (1978) Vapour pressures and sublimation enthalpies of urea and some of its derivatives. J Chem Thermodyn 9:915–923. doi: 10.1016/0021-9614(87)90038-3 Google Scholar
  32. 32.
    Emel’yanenko VN (2006) Measurement and prediction of thermochemical properties: improved increments for the estimation of enthalpies of sublimation and standard enthalpies of formation of alkyl derivatives of urea. J Chem Eng Data 51:79–87. doi: 10.1021/je050230z CrossRefGoogle Scholar
  33. 33.
    Zaitsau DZ, Kabo GJ, Kozyro AA, Sevruk VM (2003) The effect of the failure of isotropy of a gas in an effusion cell on the vapor pressure and enthalpy of sublimation for alkyl derivatives of carbamide. Thermochimica Acta 406:17–28. doi: 10.1016/S0040-6031(03)00231-4 CrossRefGoogle Scholar
  34. 34.
    De Wit HGM, van Miltenburg JC, De Kruif CG (1983) Thermodynamic properties of molecular organic crystals containing nitrogen, oxygen, and sulphur 1. Vapour pressures and enthalpies of sublimation. J Chem Thermodyn 15:651–663. doi: 10.1016/002-9614(83)90079-4 CrossRefGoogle Scholar
  35. 35.
    Gora RW, Bartkowiak W, Roszak S, Leszczynski J (2002) A new theoretical insight into the nature of intermolecular interactions in the molecular crystal of urea. J Chem Phys 117:1031–1039. doi: 10.1063/1.1482069 CrossRefGoogle Scholar
  36. 36.
    Tsuziki S, Orita H, Honda K, Mikami M (2010) First-principles lattice energy calculation of urea and hexamine crystals by a combination of periodic DFT and MP2 two-body interaction energy calculations. J Phys Chem B 114:6799–6805. doi: 10.1021/jp912028q CrossRefGoogle Scholar
  37. 37.
    Brunsteiner M, Price SL (2001) Morphologies of organic crystals: sensitivity of attachment energy predictions to the model intermolecular potential. Cryst Growth Des 1:447–453. doi: 10.1021/cg015541u CrossRefGoogle Scholar
  38. 38.
    Boek ES, Feil D, Briels WJ, Bennema P (1991) From wave function to crystal morphology: Application to urea and alpha-glycine. J Cryst Growth 114:389–410. doi: 10.1016/0022-0248(91)90057-C CrossRefGoogle Scholar
  39. 39.
    Kabo G Ya, Miroshnichenko EA, Frenkel ML, Kozyro AA, Simirskii VV, Krasulin AP, Vorob'eva VP, Lebedev Yu A (1990) Thermochemistry of urea alkyl derivatives. Bull Acad Sci USSR, Div Chem Sci 662-667Google Scholar
  40. 40.
    Stephenson RM, Malanowski S (1987) Handbook of the thermodynamics of organic compounds. Elsevier, New YorkCrossRefGoogle Scholar
  41. 41.
    Trimble LE, Voorhoeve RJH (1978) Continuous colorimetric monitoring of vapour-phase urea and cyanates. Analyst 103:759–765. doi: 10.1039/AN9780300759 CrossRefGoogle Scholar
  42. 42.
    Bradley RS, Cleasby TG (1953) The vapour pressure and lattice energy of hydrogen-bonded crystals. Part I. Oxamide, oxamic acid, and rubeanie acid. J Chem Soc London 1681-16.Google Scholar
  43. 43.
    Paorici C, Zha M, Zanotti L, Attolini G, Traldi P, Catinella S (1995) Thermodynamic analysis of urea physical vapour transport. Cryst Res Technol 30:667–675. doi: 10.1002/crat.2170300513 CrossRefGoogle Scholar
  44. 44.
    Aylward GH, Findlay TJV (1986) Datensammlung Chemie in SI Einheiten, 2nd edn. Chemie, WeinheimGoogle Scholar
  45. 45.
    Tartaglino U, Zykova-Timan T, Ercolessi F, Tosatti E (2005) Melting and nonmelting of solid surfaces and nanosystems. Phys Reports 411:291–321. doi: 10.1016/j.physrep.2005.01.004 CrossRefGoogle Scholar
  46. 46.
    Weiner SJ, Kollman PA, Case DA, Singh UC, Ghio C, Alagona G, Profeta S, Weiner P (1984) A new force field for molecular mechanical simulation of nucleic acids and proteins. J Am Chem Soc 106:765–784. doi: 10.1021/ja00315a051 CrossRefGoogle Scholar
  47. 47.
    Haleblian J, McCrone W (1969) Pharmaceutical applications of polymorphism. J Pharm Sci 58:911–929. doi: 10.1002/jps.2600580802 CrossRefGoogle Scholar
  48. 48.
    Coombes DS, Catlow CRA, Gale JD, Hardy MJ, Saunders MR (2002) Theoretical and experimental investigations on the morphology of pharmaceutical crystals. J Pharm Sci 91:1652–1658. doi: 10.1002/jps.10148 CrossRefGoogle Scholar
  49. 49.
    Anwar J, Zahn D (2011) Uncovering molecular processes in crystal nucleation and growth by using molecular simulation. Angewandte Chem Int Edn 50:1996–2013. doi: 10.1002/anie.201000463 CrossRefGoogle Scholar
  50. 50.
    Kawska A, Brickmann J, Hochrein O, Zahn D (2005) From amorphous aggregates to crystallites: modelling studies of crystal growth in vacuum. Z Anorg Allg Chem 631:1172–1176. doi: 10.1002/zaac.200400548 CrossRefGoogle Scholar
  51. 51.
    Kawska A, Brickmann J, Kniep R, Hochrein O, Zahn D (2006) An atomistic simulation scheme for modeling crystal formation from solution. J Chem Phys 124:024513-1-024513-7. doi: 10.1063/1.2145677 Google Scholar
  52. 52.
    Kawska A, Duchstein P, Hochrein O, Zahn D (2008) Atomistic mechanisms of ZnO aggregation from ethanolic solution: ion association. Proton Transfer, and Self-Organization Nano Lett 8:2336–2340. doi: 10.1021/nl801169x Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Gül Altınbaş Özpınar
    • 1
    • 2
    • 3
  • Frank R. Beierlein
    • 2
    • 3
  • Wolfgang Peukert
    • 3
    • 4
  • Dirk Zahn
    • 2
    • 3
  • Timothy Clark
    • 2
    • 3
  1. 1.Department of ChemistryNatural Sciences, Architecture and Engineering Faculty, Bursa Technical UniversityOsmangaziTurkey
  2. 2.Computer-Chemie-Centrum and Interdisciplinary Center for Molecular MaterialsFriedrich-Alexander Universität Erlangen-NürnbergErlangenGermany
  3. 3.Excellence Cluster Engineering of Advanced MaterialsFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany
  4. 4.Lehrstuhl für Feststoff- und GrenzflächenverfahrenstechnikFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Personalised recommendations