Preparation, characterization and molecular modelling of inclusion complex between α-naphthylacetic acid with ethylenediamine-β-cyclodextrin

  • Zhendong Li
  • Huijun LiuEmail author
  • Caixia Qi
  • Aohui Yang
  • Shanxia Deng
Original Article


Using ethylenediamine-β-cyclodextrin and α-naphthylacetic acid as raw material, a novel inclusion complex (en-β-CD@NAA) was synthesized. The inclusion complex structures and properties were analyzed by reliable spectroscopic and physicochemical techniques. The stoichiometry of the inclusion complex was 1:1 and the stability constant (KS) value was found to be 2511 M−1 at 293 K. Molecular thermodynamic parameters indicated that the spontaneous and exothermic nature of the process. The inclusion form was foreseen by Chem 3D program combined with 1H-NMR experimental data. The solubilization curves (K1 = 2.05) and in-vitro dissolution data demonstrated that the en-β-CD@NAA inclusion complex has satisfactory water solubility.


Ethylenediamine-β-cyclodextrin Inclusion complex Molecular modelling Thermodynamics 



This work was supported by Nature Science Foundation of China (No. 11375084), the Nature Science Foundation of Hunan (No. 2017JJ4046), Hunan Provincial Innovation Foundation For Postgraduate (No. CX2017B523).


  1. 1.
    Fenyvesi, Ã, Vikmon, M., Szente, L.: Cyclodextrins in food technology and human nutrition: benefits and limitations. Crit. Rev. Food Sci. Nutr. 56, 1981–2004 (2016)CrossRefGoogle Scholar
  2. 2.
    Stella, V.J., He, Q.: Cyclodextrins. Toxicol. Pathol. 36, 30–42 (2008)CrossRefGoogle Scholar
  3. 3.
    Higginbottom, A., Short, W.F.: 1-Naphthylacetic acid. Recl. Trav. Chim. Pays-Bas 53, 1141–1141 (2015)CrossRefGoogle Scholar
  4. 4.
    Jin-Hua, L.I., Hao, L.I., Lin, M., Sun, K.D., Tang, C.L., Zhou, X.R.: Effects of compound sodium nitrophenolate and 1-naphthylacetic acid on cutting efficiency of bauhinia blakeana. Guangxi For. Sci. 2, 204–207 (2016)Google Scholar
  5. 5.
    Milić, B., Tarlanović, J., Keserović, Z., Zorić, L., Blagojević, B., Magazin, N.: The growth of apple central fruits as affected by thinning with NAA, BA and naphthenic acids. Erwerbs Obstbau 59, 1–9 (2016)Google Scholar
  6. 6.
    Aloisio, C., Antimisiaris, S.G., Longhi, M.R.: Liposomes containing cyclodextrins or meglumine to solubilize and improve the bioavailability of poorly soluble drugs. J. Mol. Liq. 229, 106–113 (2017)CrossRefGoogle Scholar
  7. 7.
    Bulani, V.D., Kothavade, P.S., Kundaikar, H.S., Gawali, N.B., Chowdhury, A.A., Degani, M.S.: Inclusion complex of ellagic acid with β-cyclodextrin: characterization and in vitro anti-inflammatory evaluation. J. Mol. Struct. 1105, 308–315 (2016)CrossRefGoogle Scholar
  8. 8.
    Ding, L., He, J., Huang, L., Lu, R.: Studies on a novel modified β-cyclodextrin inclusion complex. J. Mol. Struct. 979, 122–127 (2010)CrossRefGoogle Scholar
  9. 9.
    Zhu, J.Y., Liu, L., Lu, C.S., Meng, Q.J.: Inclusion compound of β-cyclodextrin with p-azidobenzoic acid. Chin. J. Org. Chem. 23, 1303–1305 (2003)Google Scholar
  10. 10.
    Michalska, P., Wojnicz, A., Ruiz-Nuño, A., Abril, S., Buendia, I., León, R.: Inclusion complex of ith12674 with 2-hydroxypropyl-β-cyclodextrin: preparation, physical characterization and pharmacological effect. Carbohydr. Polym. 157, 94–104 (2017)CrossRefGoogle Scholar
  11. 11.
    Peng, L., Liu, H.J., Hu, C.: Terephthaloyl chloride bridged bis(β-cyclodextrin) and their synergetic bonding behaviors with dyes. Chin. J. Org. Chem. 35, 1330–1334 (2015)CrossRefGoogle Scholar
  12. 12.
    Silva, M., Pérezquintanilla, D., Morantezarcero, S., Sierra, I., Marina, M.L., Aturki, Z.: Ordered mesoporous silica functionalized with β-cyclodextrin derivative for stereoisomer separation of flavanones and flavanone glycosides by nano-liquid chromatography and capillary electrochromatography. J. Chromatogr. A 1490, 166–176 (2017)CrossRefGoogle Scholar
  13. 13.
    D’Aria, F., Serri, C., Niccoli, M., Mayol, L., Quagliariello, V., Iaffaioli, R.V.: Host–guest inclusion complex of quercetin and hydroxypropyl-β-cyclodextrin. J. Therm. Anal. Calorim. 1, 1–6 (2017)Google Scholar
  14. 14.
    Li, J.F., Zhang, J.X., Wang, Z.G., Yao, Y.J., Han, X., Zhao, Y.L.: Identification of a cyclodextrin inclusion complex of antimicrobial peptide cm4 and its antimicrobial activity. Food Chem. 221, 296–301 (2017)CrossRefGoogle Scholar
  15. 15.
    Misiuk, W., Jozefowicz, M.: Study on a host–guest interaction of hydroxypropyl-β-cyclodextrin with ofloxacin. J. Mol. Liq. 202, 101–106 (2015)CrossRefGoogle Scholar
  16. 16.
    Wei, Y., Zhang, J., Zhou, Y., Bei, W., Li, Y., Yuan, Q.: Characterization of glabridin/hydroxypropyl-β-cyclodextrin inclusion complex with robust solubility and enhanced bioactivity. Carbohydr. Polym. 159, 152–160 (2017)CrossRefGoogle Scholar
  17. 17.
    Yuan, C., Jin, Z., Xu, X., Zhuang, H., Shen, W.: Preparation and stability of the inclusion complex of astaxanthin with hydroxypropyl-β-cyclodextrin. Food Chem. 109, 264–268 (2008)CrossRefGoogle Scholar
  18. 18.
    Peña, A.M.D.L., Salanas, F., Gómez, M.J., Acedo, M.I., Peña, M.S.: Absorptiometric and spectrofluorimetric study of the inclusion complexes of 2-naphthyloxyacetic acid and 1-naphthylacetic acid with β-cyclodextrin in aqueous solution. J. Incl. Phenom. Macrocycl. Chem. 15, 131–143 (1993)CrossRefGoogle Scholar
  19. 19.
    Wang, E.J., Chen, G.Y., Chang, R.: Crystal structure of a novel sandwich inclusion complex of β-cyclodextrin with a-naphthylacetic acid. Chem. Res. Chin. Univ. 27, 730–733 (2011)Google Scholar
  20. 20.
    Gu, J., Chi, S.M., Zhao, Y., Zheng, P., Ruan, Q., Zhao, Y.: Inclusion complexes of coenzyme Q10 with polyamine-modified β-cyclodextrins: characterization, solubilization, and inclusion mode. Helv. Chim. Acta 94, 1608–1617 (2011)CrossRefGoogle Scholar
  21. 21.
    Lv, P., Liu, M., Liao, R., Zhao, Y., Liao, X., Gao, C.: Host–guest inclusion system of rhein with polyamine-modified β-cyclodextrins: characterization and cytotoxicity. Pharm. Dev. Technol. 22, 669–677 (2016)CrossRefGoogle Scholar
  22. 22.
    Xiao, D., Yang, B., Zhao, Y.L., Liao, X.L., Yang, X.M., Wang, F.: Inclusion complexes of dihydroartemisinin with cyclodextrin and its derivatives: characterization, solubilization and inclusion mode. J. Incl. Phenom. Macrocycl. Chem. 79, 349–356 (2014)CrossRefGoogle Scholar
  23. 23.
    Wang, Y.L., Feng, R.S., Guo, Y.J.: Heterogeneous synthesis of mono 6-deoxy-tosyl-β-cyclodextrin in alkaline. Chin. J. Appl. Chem. 28, 1269–1273 (2011)Google Scholar
  24. 24.
    Benesi, H.A., Hildebrand, J.H.: A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. J. Am. Chem. Soc. 71, 2703–2707 (1949)CrossRefGoogle Scholar
  25. 25.
    Caso, J.V., Russo, L., Palmieri, M., Malgieri, G., Galdiero, S., Falanga, A.: Investigating the inclusion properties of aromatic amino acids complexing β-cyclodextrins in model peptides. Amino Acids 47, 2215–2227 (2015)CrossRefGoogle Scholar
  26. 26.
    Araújo, M.V.G.D., Vieira, E.K.B., Lázaro, G.S., Conegero, L.S., Almeida, L.E., Barreto, L.S.: Sulfadiazine/hydroxypropyl-β-cyclodextrin host–guest system: characterization, phase-solubility and molecular modeling. Bioorgan. Med. Chem. 16, 5788–5794 (2008)CrossRefGoogle Scholar
  27. 27.
    Liu, M., Lv, P., Lia, R., Zhao, Y., Yang, B.: Synthesis, characterization and biological activity of rhein-cyclodextrin conjugate. J. Mol. Struct. 1128, 239–244 (2016)CrossRefGoogle Scholar
  28. 28.
    Melo, P.N.D., Barbosa, E.G., Caland, L.B.D., Carpegianni, H., Garnero, C., Longhi, M.: Host–guest interactions between benznidazole and beta-cyclodextrin in multicomponent complex systems involving hydrophilic polymers and triethanolamine in aqueous solution. J. Mol. Liq. 186, 147–156 (2013)CrossRefGoogle Scholar
  29. 29.
    Nazaro, V.B., Avakyan, V.G., Fomina, M.V., Vedernikov, A.I., Alfimov, M.V., Gromov, S.P.: Spectral properties of protonated naphthylpyridine in the presence of cyclodexrins. Russ. Chem. Bull. 62, 2150–2157 (2013)CrossRefGoogle Scholar
  30. 30.
    Rungnim, C., Phunpee, S., Kunaseth, M.: Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex. Beilstein J. Org. Chem. 11, 2306–2318 (2015)CrossRefGoogle Scholar
  31. 31.
    Cramer, F., Saenger, W., Spatz, H.C.: Inclusion compounds. XIX.1a the formation of inclusion compounds of α-cyclodextrin in aqueous solutions. thermodynamics and kinetics. J. Am. Chem. Soc. 89, 14–20 (1967)CrossRefGoogle Scholar
  32. 32.
    Hao, A.Y., Tong, L.H., Zhang, F.S., Gao, X.M.: Convenient preparation of monoacylated β-cyclodextrin (cyclomaltoheptaose) on the secondary hydroxyl side. Carbohydr. Res. 277, 333–337 (1995)CrossRefGoogle Scholar
  33. 33.
    Izadmanesh, Y., Ghasemi, J.B.: Thermodynamic study of β-cyclodextrin-dye inclusion complexes using gradient flow injection technique and molecular modeling. Spectrochim. Acta 165, 54–60 (2016)CrossRefGoogle Scholar
  34. 34.
    Chakraborty, S., Basu, S., Lahiri, A., Basak, S.: Inclusion of chrysin in β-cyclodextrin nanocavity and its effect on antioxidant potential of chrysin: a spectroscopic and molecular modeling approach. J. Mol. Struct. 977, 180–188 (2010)CrossRefGoogle Scholar
  35. 35.
    Roy, M.N., Saha, S., Kundu, M.: Exploration of inclusion complexes of neurotransmitters with β-cyclodextrin by physicochemical techniques. Chem. Phys. Lett. 655–656, 43–50 (2016)CrossRefGoogle Scholar
  36. 36.
    Desai, C., Prabhakar, B.: Nano-amorphous composites of cilostazol–HP-β-CD inclusion complexes: physicochemical characterization, structure elucidation, thermodynamic studies and in vitro evaluation. J. Incl. Phenom. Macrocycl. Chem. 81, 175–191 (2015)CrossRefGoogle Scholar
  37. 37.
    Ol’Khovich, M.V., Sharapova, A.V., Lavrenov, S.N., Blokhina, S.V., Perlovich, G.L.: Inclusion complexes of hydroxypropyl-β-cyclodextrin with novel cytotoxic compounds: solubility and thermodynamic properties. Fluid Phase Equilib. 384, 68–72 (2014)CrossRefGoogle Scholar
  38. 38.
    Padhan, P., Sethy, A., Behera, P.K.: Host–guest interaction between ofloxacin-β-cyclodextrin complexes in acidic and neutral pH: a fluorescence quenching study. J. Photochem. Photobiol. A Chem. 337, 165–171 (2017)CrossRefGoogle Scholar
  39. 39.
    Hao, J., Wang, A.Y., Zhang, M.M.: Dissolution and physiological activity of α-naphthylacetic acid/β-cyclodextrin inclusion complexes. Jangsu Agric. Sci. 41, 75–82 (2013)Google Scholar
  40. 40.
    Yong, G., Hongwu, T., Liang, Z., et al.: Solubilization of cholesterol by ethylenediamine-β-cyclodextrin. Sci. Technol. Food Ind. 23(3), 32–33 (2002)Google Scholar
  41. 41.
    Jiang, S., Li, J.N., Jiang, Z.T.: Inclusion reactions of β-cyclodextrin and its derivatives with cinnamaldehyde in cinnamomum loureirii essential oil. Eur. Food Res. Technol. 230, 543–550 (2010)CrossRefGoogle Scholar

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.College of Chemistry and Chemical EngineeringUniversity of South ChinaHengyangChina

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