Topological models for prediction of adductability of substituted cyclic organic compounds in urea

  • Seema Thakral
  • A. K. Madan
Original article


The relationship of urea adductability of substituted cyclic organic compounds with topological descriptors has been investigated. Wiener’s index—a distance-based topological descriptor, molecular connectivity index—an adjacency-based topological descriptor and eccentric connectivity index—an adjacency-cum-distance based topological descriptor were employed for the present study. A data set comprising of 45 cyclic organic compounds was utilized. The values of all the three topological indices for every compound involved in the data set were computed using in-house computer program. The resultant data was analyzed and suitable models were developed after identification of adductible ranges. Subsequently, each compound in the data set was classified using these models either as urea adductible or non-adductible, which was then compared with the reported adductability in urea. Accuracy of prediction was found to vary from a minimum of 90% for a model based upon eccentric connectivity index to a maximum of 92% for model based upon Wiener’s index. Statistical analysis revealed the selected topological indices to be weakly or appreciably intercorrelated for the said data set.


Eccentric connectivity index Molecular connectivity index Wiener’s index Topological descriptors Urea adductability Urea inclusion compounds 


  1. 1.
    Hollingsworth, M.D., Harris, K.D.M.: Urea inclusion compounds. In: Atwood, J.L., Davis, J.E.D., Macnicol, D.D., Vogtle, F. (eds.) Comprehensive Supramolecular Chemistry. Solid State Supramolecular Chemistry-Crystal Engineering, vol. 6, pp. 177–237. Pergamon Press, Oxford (1996).Google Scholar
  2. 2.
    Harris, K.D.M.: Urea Inclusion Compounds. In: Atwood, J.L., Steed, J.W. (eds.) Encyclopedia of Supramolecular Chemistry, vol. 2, pp. 1538–1549. Marcel Dekker, New York (2004).Google Scholar
  3. 3.
    Vaughan, P., Donohue, J.: The structure of urea. Interatomic distances and resonance in urea and related compounds. Acta Crystallogr. 5, 530–535 (1952).CrossRefGoogle Scholar
  4. 4.
    Smith, A.E.: The crystal structure of urea–hydrocarbon complexes. Acta Crystallogr. 5, 224–235 (1952).CrossRefGoogle Scholar
  5. 5.
    Harris, K.D.M., Thomas, J.M.: Structure aspects of urea inclusion compounds and their investigations by x-ray diffraction: a general discussion. J. Chem. Soc., Faraday Trans. 86, 2985–2996 (1990).CrossRefGoogle Scholar
  6. 6.
    Frank, S.G.: Inclusion compounds. J. Pharm. Sci. 64, 1585–1604 (1975).CrossRefGoogle Scholar
  7. 7.
    Harris, K.D.M., Smart, S.S., Hollingsworth, M.D.: Structural properties of α, ω-dibromoalkane/urea inclusion compounds: a new type of interchannel guest molecule ordering. J. Chem. Soc. Faraday Trans. 87, 3423–3429 (1991).CrossRefGoogle Scholar
  8. 8.
    Clement, R., Mazieres, C., Guibe, L.: Low temperature phase transition in urea-trioxane inclusion compounds. J. Solid State Chem. 5, 436–440 (1972).CrossRefGoogle Scholar
  9. 9.
    Lenne, H.U., Mez, H.C., Schlenk, W.: The lengths of molecules in inclusion channels of urea and thiourea. Liebigs Ann. Chem. 73, 70–96 (1968).Google Scholar
  10. 10.
    Smart, S.S., Baghdadi, A.E., Guillaume, F., Harris, K.D.M.: Conformational and vibrational properties of α, ω- dihalogenoalkane/urea inclusion compounds: a Raman scattering investigation. J. Chem. Soc. Faraday Trans. 90, 1313–1322 (1994).CrossRefGoogle Scholar
  11. 11.
    Hayes, D.G., Alstine, J.V., Setterwall, F.: Urea-based fractionation of fatty acids and glycerides of polyunsaturated and hydroxy fatty acid seed oils. J. Am. Oil Chem. Soc. 77, 207–215 (2000).CrossRefGoogle Scholar
  12. 12.
    Bishop, R., Dance, I.G.: New type of helical inclusion networks. Top. Curr. Chem. 149, 139–188 (1988).Google Scholar
  13. 13.
    Takemoto, K., Sonoda, N.: Inclusion compounds of urea, thiourea and selenourea. In: Atwood, J.W., Davis, J.E.D., MacNicol, D.D. (eds.) Inclusion Compounds, vol. 2, pp. 47–67. Academic Press, London (1984).Google Scholar
  14. 14.
    Findlay, R.A.: Adductive crystallization. In: Schoen, H.M., Mcketta, J.J. (eds.) Interscience Library of Chemical Engineering and Processing. New Chemical Engineering Separation Techniques, vol. 1, pp. 257–318. Interscience Publishers, New York (1962).Google Scholar
  15. 15.
    Thakral, S., Madan, A.K.: Topological models for prediction of adductability of branched aliphatic compounds in urea. J. Inclusion Phemon. Macrocyclic Chem. 56, 405–412 (2006).CrossRefGoogle Scholar
  16. 16.
    Estrada, E., Uriate, E.: Recent advances on the role of topological indices in drug discovery research. Current Med. Chem. 8, 1573–1588 (2001).Google Scholar
  17. 17.
    Nikolic, S., Kovacevic, G., Milicevic, A., Trinajstic, N.: The Zagreb Indices: thirty years after. Croat. Chem. Acta 76, 113–124 (2003).Google Scholar
  18. 18.
    Gozalbes, R., Doucet, J., Derouin, F.: Application of topological descriptors in QSAR and drug design: history and new trends. Curr. Drug Targets Infect. Disord. 2, 93–102 (2002).CrossRefGoogle Scholar
  19. 19.
    Wiener, H.: Correlation of heats of isomerization, and differences in heats of vaporization of isomers, among the paraffin hydrocarbons. J. Am. Chem. Soc. 69, 2636–2638 (1947).CrossRefGoogle Scholar
  20. 20.
    Wiener, H.: Structural determination of paraffin boiling points. J. Am. Chem. Soc. 69, 17–20 (1947).CrossRefGoogle Scholar
  21. 21.
    Balaban, A.T.: Topological indices based on topological distances in molecular graphs. Pure Appl. Chem. 55(2), 199–206 (1983).Google Scholar
  22. 22.
    Hosoya, H.: Topological indices as a sorting device for coding chemical structures. J. Chem. Doc. 12, 181–183 (1972).CrossRefGoogle Scholar
  23. 23.
    Randic, M.: On characterization of molecular branching. J. Am. Chem. Soc. 97(23), 6609–6615 (1975).CrossRefGoogle Scholar
  24. 24.
    Gutman, I., Randic, M.: Algebraic characterization of skeletal branching. Chem. Phys. Lett. 47, 15–19 (1977).CrossRefGoogle Scholar
  25. 25.
    Sharma, V., Goswami, R., Madan, A.K.: Eccentric connectivity index: a novel highly discriminating topological descriptor for structure-property and structure-activity studies. J. Chem. Inf. Comput. Sci. 37, 273–282 (1997).CrossRefGoogle Scholar
  26. 26.
    Kumar, V., Madan, A.K.: Topological models for the prediction of cyclindependent kinase 2 inhibitory activity of aminothiazoles. MATCH Commun. Math. Comput. Chem. 51, 59–78 (2004).Google Scholar
  27. 27.
    Swern, D.: Urea and thiourea complexes in separating organic compounds. Ind. Eng. Chem. 47, 216–221 (1955).CrossRefGoogle Scholar
  28. 28.
    Schiessler, R.W., Flitter, D.: Urea and thiourea adduction of C5–C42-hydrocarbons. J. Am. Chem. Soc. 74, 1720–1723 (1950).CrossRefGoogle Scholar
  29. 29.
    Truter, E.V.: Urea complexes of some branched-chain and cyclic esters. J. Chem. Soc. 2416–2419 (1951).Google Scholar
  30. 30.
    Linstead, R.P., Whallwy, M.: The formation of crystalline complexes between urea and esters, and their application to separation of mixtures of esters. J. Chem. Soc. 2987–2989 (1950).Google Scholar
  31. 31.
    Zimmerschied, W.J., Dinerstein, R.A., Wietkamp, A.W., Marschner, R.F.: Complexes of urea with linear aliphatic compounds. J. Am. Chem. Soc. 71, 2947 (1949).CrossRefGoogle Scholar
  32. 32.
    Redlich, O., Gable, C.M., Dunlop, A.K., Millar, R.W.: Addition compounds of urea and organic substances. J. Am. Chem. Soc. 72, 4153–4160 (1950).CrossRefGoogle Scholar
  33. 33.
    Mima, H., Nishikawa, M.: Inclusion compounds of α-lipoic acid methyl ester with urea and thiourea. J. Pharm. Sci. 53, 931–934 (1964).CrossRefGoogle Scholar
  34. 34.
    Gupta, S., Singh, M., Madan, A.K.: Predicting anti-HIV activity: computational approach using a novel topological descriptor. J. Comput. Aided Mol. Des. 15, 671–678 (2001).CrossRefGoogle Scholar
  35. 35.
    Gupta, S., Singh, M., Madan, A.K.: Application of graph theory: relationship of molecular connectivity index and atomic molecular connectivity index with anti-HSV activity. J. Mol. Struct. (Theochem) 571, 142–152 (2000).Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  1. 1.GVM College of PharmacySonipatIndia
  2. 2.Faculty of Pharmaceutical SciencesM.D. UniversityRohtakIndia

Personalised recommendations