Skip to main content
SpringerLink
Log in

Host-guest complex of nabumetone: β-cyclodextrin: quantum chemical study and QTAIM analysis

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

The aim of the present work is the investigation of the inclusion complex of nabumetone (NAB) and β-cyclodextrin (β-CD) using PM3, DFT, DFT-D and ONIOM2 methods. The results indicate that the most energetically favorable structure predicts a preference of the methoxy group to enter the cavity of β-CD from its wide rim. Consequently, the butanone moiety is positioned outside the cavity on the side of the secondary hydroxyls, with a total insertion of naphthalene group. The semi-empirical PM3 results are in good agreement with those obtained by the DFT optimization (with and without dispersion correction). The donor–acceptor interactions between drug and the cavity wall of the host, studied on the basis of natural bonding orbital (NBO) analysis, show the presence of weak intermolecular hydrogen bonds in addition to the most important van der Waals interactions. Furthermore, it is revealed that among the DFT and DFT-D techniques selected to quantify these interactions, WB97X-D functional provides the greatest values of stabilization energies E(2). Finally, a detailed topological charge density analysis based on the quantum theory of atoms in molecules (QTAIM), developed by Bader and co-workers, has been accomplished using the WB97X-D and B3LYP methods on the most favorable complexes. A good correlation between the structural parameters and the electronic density is found.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Loukas, Y.l.: Complexation of haloperidol with a water-soluble β-cyclodextrin polymer: characterization of the inclusion complex in solid state and in aqueous solution. Pharm. Pharmacol. Commun. 1, 509–512 (1995)

    CAS  Google Scholar 

  2. Loukas, L.Y., Jayasekera, P., Gregoriadis, G.: Characterization and photoprotection studies of a model γ-cyclodextrin-induced photolabile drug entrapped in liposomes incorporating light absorbers. J. Phys. Chem. 99, 11035–11040 (1995)

    Article  CAS  Google Scholar 

  3. Bensouilah, N., Abdaoui, M.: Inclusion complex of N-nitroso, N-(2-chloroethyl), N,N-dibenzylsulfamid with β-cyclodextrin: fluorescence and molecular modeling. C. R. Chimie 15, 1022–1036 (2012)

    Article  CAS  Google Scholar 

  4. Fisli, H., Bensouilah, N., Dhaoui, N., Abdaoui, M.: Effects of solvent, pH and b-cyclodextrin on the fluorescent behaviour of lomustine. J. Incl. Phen. 73, 369–376 (2012)

    Article  CAS  Google Scholar 

  5. Valero, M., Costa, S.M.B., Ascenso, J.R., Velazquez, M.M., Rodriguez, L.J.: Complexation of the non-steroidal anti-inflammatory drug nabumetone with modified and unmodified cyclodextrins. J. Inc. Ph. Mac. Chem. 35, 663–677 (1999)

    CAS  Google Scholar 

  6. Saenger, W.: Cyclodextrin inclusion compounds in research and industry. Angew. Chem. Int. Ed. Engl. 19, 344–362 (1980)

    Article  Google Scholar 

  7. Szejtli, J.: Cyclodextrins and their inclusion complexes. Akademio Kaido, Budapest (1982)

    Google Scholar 

  8. Szejtli, J., Szente, L.: Interaction between indomethacin and β-cyclodextrin. Pharmazie 36, 694–696 (1985)

    Google Scholar 

  9. Rathi, P.B., Deshpande, K.V.: Determination and evaluation of solubility parameter of nabumetone using dioxane-water system. Asi. J. Bio. Phar. Sci. (03) 27, 30–33 (2013)

    Google Scholar 

  10. Tabushi, I.: Cyclodextrin catalysis as a model for enzyme action. Acc. Chem. Res. 15, 66–72 (1982)

    Article  CAS  Google Scholar 

  11. Clarke, R.J., Coates, J.H., Lincoln, S.F.: Inclusion complexes of the cyclomalto-oligosaccharides (cyclodextrins). Adv. Carbohydr. Chem. Biochem. 46, 205–249 (1988)

    Article  CAS  Google Scholar 

  12. Bader, R.W.F.: Atoms in Molecules. A Quantum Theory. Calendon Press, Oxford (1990)

    Google Scholar 

  13. Keith, T.A.: AIMALL software package, version 10.05.04 (2010)

  14. Hyperchem, release 7.51 for windows 2002 Hypercube. Inc.

  15. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G.A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H.P., Izmaylov, A.F., Bloino, J., Zheng, G., Sonnenberg, J.L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, J.A. Jr., Peralta, J.E., Ogliaro, F., Bearpark, M., Heyd, J.J., Brothers, E., Kudin, K.N., Staroverov, V.N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J.C., Iyengar, S.S., Tomasi, J., Cossi, M., Rega, N., Millam, J.M., Klene, M., Knox, J.E., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi R, Pomelli, C., Ochterski, J.W., Martin, R.L., Morokuma, K., Zakrzewski, V.G., Voth, G.A., Salvador, P., Dannenberg, J.J., Dapprich, S., Daniels, A.D., Farkas, O,, Foresman, J.B., Ortiz, J.V., Cioslowski, J., Fox, D.J.: Gaussian 09, revision A.02. Gaussian, Inc., Wallingford CT (2009)

    Google Scholar 

  16. Al-Sou’od, K.A.: Molecular mechanics study of the inclusion complexes of some 1,2,4-oxadiazole derivatives of 3,3′-bis (1,2,4-oxadiazol-5(4H)-one) with β-cyclodextrin. J. Inc. Phen. Macr. Chem. 54, 123–127 (2006)

    Article  Google Scholar 

  17. Seridi, L., Boufelfel, A.: Molecular modeling study of lamotrigine/β-cyclodextrin inclusion complex. J. Mol. Liquids 158, 151–158 (2011)

    Article  CAS  Google Scholar 

  18. Madi, F., Khatmi, D., Dhaoui, N., Bouzitouna, A., Abdaoui, A., Boucekkine, A.: Molecular model of CENS piperidine β-CD inclusion complex: DFT study. C. R. Chimie 12, 1305–1312 (2009)

    Article  CAS  Google Scholar 

  19. Liu, L., Li, X.S., Song, K.S., Guo, Q.X.: PM3 studies on the complexation of α-cyclodextrin with benzaldehyde and acetophenone. J. Mol. Struct. Theochem. 531, 127–134 (2000)

    Article  CAS  Google Scholar 

  20. Liu, L., Guo, Q.X.: Use of quantum chemical methods to study cyclodextrin chemistry. J. Inc. Phen. Macr. Chem. 50, 95–103 (2004)

    Article  CAS  Google Scholar 

  21. Yan, C., Xiu, Z., Li, X., Hao, C.: Molecular modeling study of β-cyclodextrin complexes with (+)-catechin and (–)-epicatechin. J. Mol. Graph. Mod. 26, 420–428 (2007)

    Article  CAS  Google Scholar 

  22. Dapprich, S., Komaromi, I., Byun, K.S., Morokuma, K., Frisch, M.J.: A new ONIOM implementation in Gaussian 98. Part I. The calculation of energies, gradients, vibrational frequencies and electric field derivatives. J. Mol. Struct. Theo. 461–462, 1–21 (1999)

    Article  Google Scholar 

  23. Maseras, F., Morokuma, K.: IMOMM: a new integrated ab initio + molecular mechanics geometry optimization scheme of equilibrium structures and transition states. J. Comput. Chem. 16, 1170–1179 (1995)

    Article  CAS  Google Scholar 

  24. Humbel, S., Sieber, S., Morokuma, K.: 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−. Chem. Phys. 105, 1959–1967 (1996)

    CAS  Google Scholar 

  25. Liu, L., Li, X.S., Guo, Q.X., Liu, Y.C.: Hartree-Fock and density functional theory studies on the molecular recognition of the cyclodextrin. Chin. Chem. Lett. 10, 1053–1056 (1999)

    CAS  Google Scholar 

  26. Liu, L., Li, X.S., Mu, T.W., Guo, Q.X., Liu, Y.C.: Interplay between molecular recognition and redox properties: a theoretical study of the inclusion complexation of β-cyclodextrin with phenothiazine and its radical cation. J. Inc. Phen. Macr. Chem. 38, 199–206 (2000)

    Article  CAS  Google Scholar 

  27. Zhao, Y., Schultz, N.E., Truhlar, D.G.: Exchange-correlation functional with broad accuracy for metallic and nonmetallic compounds, kinetics, and noncovalent interactions. J. Chem. Phys. 123, 161103–161106 (2005)

    Article  Google Scholar 

  28. Zhao, Y., Truhlar, D.G.: The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functional. Theor. Chem. Acc. 120, 215–241 (2008)

    Article  CAS  Google Scholar 

  29. Josa, D., Rodriguez-Otero, J., Cabaleiro-Lago, E. M., Rellan-Pineiro, M.: Analysis of the performance of DFT-D, M05-2X and M06-2X functionals for studying π⋯π interactions. Chem. Phy. Lett. 557, 170–175 (2013)

    Article  CAS  Google Scholar 

  30. Grimme, S.: Accurate description of van der Waals complexes by density functional theory including empirical corrections. J. Comput. Chem. 25, 1463–1473 (2004)

    Article  CAS  Google Scholar 

  31. Grimme, S., Anthony, J., Schwabe, T., Muck-Lichtenfeld, C.: Density functional theory with dispersion corrections for supramolecular structures, aggregates, and complexes of (bio)organic molecules. Org. Biomol. Chem. 5, 741–758 (2007)

    Article  CAS  Google Scholar 

  32. Becke, A.D., Johnson, E.R.: Exchange-hole dipole moment and the dispersion interaction revisited. J. Chem. Phys. 127, 154108–154113 (2007)

    Article  Google Scholar 

  33. Steinmann, S.N., Corminboeuf, C.: A generalized-gradient approximation exchange hole model for dispersion coefficients. J. Chem. Phys. 134, 044117–044121 (2011)

    Article  Google Scholar 

  34. Tkatchenko, A., Scheffler, M.: Accurate molecular van der Waals interactions from ground-state electron density and free-atom reference dataphys. Rev. Lett. 102, 073005–073008 (2009)

    Article  Google Scholar 

  35. Krishtal, A., Vanommeslaeghe, K., Olasz, A., Veszpremi, T., Van Alsenoy, C., Geerlings, P.: Accurate interaction energies at density functional theory level by means of an efficient dispersion correction. J. Chem. Phys. 130, 174101 (2009). doi:10.1063/1.3126248

    Article  Google Scholar 

  36. Sato, T., Nakai, H.: Local response dispersion method. II. Generalized multicenter interactions. J. Chem. Phys. 133, 194101–194109 (2010)

    Article  Google Scholar 

  37. Dabbagh, H.A., Zamani, M., Farrokhpour, H.: DFT investigation of endohedral boron oxide nanocapsules: encapsulation of He, Ne, Ar, H, N, and Cl atoms. Chem. Phys. 393, 86–95 (2012)

    Article  CAS  Google Scholar 

  38. Becke, A.D.: Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A 38, 3098–3100 (1988)

    Article  CAS  Google Scholar 

  39. Grimme, S.: Semi-empirical GGA-type density functional constructed with a long-range dispersion correction. J. Comput. Chem. 27, 1787–1799 (2006)

    Article  CAS  Google Scholar 

  40. Chai, J.-D., Head-Gordon, M.: Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys. Chem. Chem. Phys. 10, 6615–6620 (2008)

    Article  CAS  Google Scholar 

  41. Jurečka, P., Černý, J., Hobza, P., Salahub, D.R.: Density functional theory augmented with an empirical dispersion term. Interaction energies and geometries of 80 noncovalent complexes compared with ab initio quantum mechanics calculations. J. Comput. Chem. 28, 555–569 (2007)

    Article  Google Scholar 

  42. Raju, R.K., Ramraj, A., Hillier, I.H., Vincent, M.A., Burton, N.A.: Carbohydrate–aromatic π interactions: a test of density functionals and the DFT-D method. Phys. Chem. Chem. Phys. 11, 3411–3416 (2009)

    Article  CAS  Google Scholar 

  43. Jha, P.C., Rinkevicius, Z., Agren, H., Seal, P., Chakrabarti, S.: Searching of potential energy curves for the benzene dimer using dispersion-corrected density functional theory. Phys. Chem. Chem. Phys. 10, 2715–2721 (2008)

    Article  CAS  Google Scholar 

  44. Lin, I.C., Roethlisberger, U.: Describing weak interactions of biomolecules with dispersion-corrected density functional theory. Phys. Chem. Chem. Phys. 10, 2730–2734 (2008)

    Article  CAS  Google Scholar 

  45. Morgado, C.A., Hillier, I.H., Burton, N.A., Mc Douall, J.J.W.: A QM/MM study of fluoroaromatic interactions at the binding site of carbonic anhydrase II, using a DFT method corrected for dispersive interactions. Phys. Chem. Chem. Phys. 10, 2706–2714 (2008)

    Article  CAS  Google Scholar 

  46. Tongying, P., Tantirungrotechai, Y.: A performance study of density functional theory with empirical dispersion corrections and spin-component scaled second-order Møller–Plesset perturbation theory on adsorbate–zeolite interactions. J. Mol. Stru. Theo. 945, 85–88 (2010)

    Article  CAS  Google Scholar 

  47. NBO 3.1, Glendening, E.D., Reed, A.E., Carpenter, J.E., Weinhold, F.: Theoretical Chemistry Institute. University of Wisconsin, Madison (1996)

    Google Scholar 

  48. Chen, W., Chang, C.E., Gilson, M.K.: Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design. Bioph. J. 87, 3035–3049 (2004)

    Article  CAS  Google Scholar 

  49. Hermans, J., Wang, L.: Inclusion of loss of translational and rotational freedom in theoretical estimates of free energies of binding. Application to a complex of benzene and mutant T4 lysozyme. J. Am. Chem. Soc. 119, 2707–2714 (1997)

    Article  CAS  Google Scholar 

  50. Strajbl, M., Sham, Y.Y., Villa, J., Chu, Z.T., Warshel, A.: Calculations of activation entropies of chemical reactions in solution. J. Phys. Chem. B 104, 4578–4584 (2000)

    Article  CAS  Google Scholar 

  51. Gornas, P., Neunert, G., Baczynski, K., Polewski, K.: β-Cyclodextrin complexes with chlorogenic and caffeic acids from coffee brew: spectroscopic, thermodynamic and molecular modelling study. Food. Chem. 114, 190–196 (2009)

    Article  CAS  Google Scholar 

  52. Zhou, Z., Parr, R.G.: Activation hardness: new index for describing the orientation of electrophilic aromatic substitution. J. Am. Chem. Soc. 112, 5720–5724 (1990)

    Article  CAS  Google Scholar 

  53. Singh, R.K., Verma, S.K., Sharma, P.D.: DFT based Study of interaction between frontier orbitals of transition metal halides and thioamides. Int. J. Chem. Tech. Res. 3, 1571–1579 (2011)

    CAS  Google Scholar 

  54. Pearson, R.G.: Hard and soft acids and bases: the evolution of a chemical concept. Coord. Chem. Rev. 100, 403–425 (1990)

    Article  CAS  Google Scholar 

  55. Gaudio, A.C., Korolkovas, A.: Quantitative structure-activity relationships for 1,4-dihydropyridine calcium channel antagonists (nifedipine analogues): a quantum chemical/classical approach. J. Pharma. Sci. 83, 1110–1115 (1994)

    Article  CAS  Google Scholar 

  56. Seridi, L., Boufelfel, A.: Wogonin hosted @ β-cyclodextrin: structural, electronic and nuclear studies. J. Mol. Liquids. 188, 13–21 (2013)

    Article  CAS  Google Scholar 

  57. Ruangpornvisuti, V., Wanno, B.: Molecular model for host–guest interaction of tetra amino-tert-butylthiacalix[4]arene and tetraamino-tert-butylcalix[4]arene receptors with carboxylate and dicarboxylate guests: an ONIOM study. J Mol Model 13, 65–77 (2007)

    Article  CAS  Google Scholar 

  58. Reed, A.E., Curtiss, L.A., Weinhold, F.: Intermolecular interactions from a natural bond orbital, donor-acceptor view point. Chem. Rev. 88, 899–926 (1988)

    Article  CAS  Google Scholar 

  59. Uccello-Barretta, G., Balzano, F., Sicoli, G., Fríglola, C., Aldana, I., Monge, A., Paolino, D., Guccione, S.: Combining NMR and molecular modelling in a drug delivery context: investigation of the multi-mode inclusion of a new NPY-5 antagonist bromobenzenesulfonamide into β-cyclodextrin. Bioorg. Med. Chem. 12, 447–458 (2004)

    Article  CAS  Google Scholar 

  60. Koch, U., Popelier, P.L.A.: Characterization of C–H–O hydrogen bonds on the basis of the charge density. J. Phys. Chem. 99, 9747–9754 (1995)

    Article  CAS  Google Scholar 

  61. Parthasarathi, R., Subramanian, V., Sathyamurthy, N.: Hydrogen bonding without borders: an atoms-in-molecules perspective. J. Chem. Phys. A Lett. 110, 3349–3351 (2006)

    CAS  Google Scholar 

  62. Cremer, D., Kraka, E.: Chemical bonds without bonding electron density-does the difference electron-density analysis suffice for a description of the chemical bond? Angew. Chem., Int. Ed. Engl. 23, 627–628 (1984)

    Article  Google Scholar 

  63. Rozas, I., Alkorta, I., Elguero, J.: Behavior of ylides containing N, O, and C atoms as hydrogen bond acceptors. J. Am. Chem. Soc. 122, 11154–11161 (2000)

    Article  CAS  Google Scholar 

  64. Tehrani, Z.A., Shakourian-Fard, M., Fattahi, A.: Computational investigation of thermochemical properties of non-natural C-nucloebases: different hydrogen-bonding preferences for non-natural Watson–Crick base pairs. Struct. Chem. 24, 1015–1025 (2013). doi:10.1007/s11224-012-0115-y

    Article  Google Scholar 

  65. Grabowski, S.J., Andrzej Sokalski, W., Leszczynskin, J.: Wide spectrum of H…H interactions: van der Waals contacts, dihydrogen bonds and covalency. Chem. Phys. 337, 68–76 (2007)

    Article  CAS  Google Scholar 

  66. Espinosa, E., Molins, E., Lecomte, C.: Hydrogen bond strengths revealed by topological analyses of experimentally observed electron densities. Chem. Phys. Lett. 285, 170–173 (1998)

    Article  CAS  Google Scholar 

  67. Baryshnikov, G.V., Minaev, B.F., Minaeva, V.A., Baryshnikova, A.T., Pittelkow, M.: DFT and QTAIM study of the tetra-tert-butyltetraoxa[8]circulene regioisomers structure. J. Mol. Struc. 1026, 127–132 (2012)

    Article  CAS  Google Scholar 

  68. Liu, L., Guo, Q.X.: The driving forces in the inclusion complexation of cyclodextrin. J. Inc. Phen. Mac. Chem. 42, 1–14 (2002)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Algerian minister of higher education and scientific research through the CNEPRU research grants.

Author information

Authors and Affiliations

  1. Laboratory of Applied Organic Chemistry, Faculty of Chemistry (LAOC), University of Sciences and Technology Houari Boumediene, USTHB, BP 32, El-Alia, 16111, Bab-Ezzouar, Algiers, Algeria

    Nadjia Bensouilah & Baya Boutemeur-Kheddis

  2. Laboratory of Applied Chemistry (LAC), 08 Mai 45 University, Guelma, 24000, Algeria

    Nadjia Bensouilah & Mohamed Abdaoui

  3. Mechanics and Structures Research Laboratory (LMS), May 8th 1945 University, P.O. Box 401, 24000, Guelma, Algeria

    Hamza Bensouilah & Ikhlas Meddour

Authors
  1. Nadjia Bensouilah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Baya Boutemeur-Kheddis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hamza Bensouilah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ikhlas Meddour
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohamed Abdaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hamza Bensouilah.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 17 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bensouilah, N., Boutemeur-Kheddis, B., Bensouilah, H. et al. Host-guest complex of nabumetone: β-cyclodextrin: quantum chemical study and QTAIM analysis. J Incl Phenom Macrocycl Chem 87, 191–206 (2017). https://doi.org/10.1007/s10847-016-0690-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-016-0690-4

Keywords

Search

Navigation