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Adsorption of Ampyra anticancer drug on the graphene and functionalized graphene as template materials with high efficient carrier

  • Najme Dastani
  • Ali ArabEmail author
  • Heidar Raissi


The adsorption of Ampyra drug on the graphene nanosheet (GNS) and functionalized graphene nanosheets (f-GNSs) with an epoxide, hydroxyl, carboxyl, and carbonyl group was investigated using DFT computations in the gas phase and aqueous solution. The optimization of different structures for GNS-Ampyra indicated that the drug molecule was attracted by its hexagonal aromatic ring, to the six-membered ring of GNS by π–π stacking interaction. By functionalization of GNS with a carboxyl group, the maximum adsorption energy obtained. By adsorption of Ampyra on functionalized nanosheets, the energy gap and global hardness decreased which indicated an increase in the reactivity of considered complexes. In addition, Ampyra adsorption increased the polarity, which revealed that the dispersion and solubility of intended complexes increased after adsorption. The values of solvation energy showed a noticeable increase in the stability of f-GNSs after adsorption of Ampyra in the presence of water solvent. The physical nature of the Ampyra adsorption represented an advantage of easy desorption of the drug molecule without any electronic or structural variation. These results confirmed that the chemical modification of GNS using the mentioned functional groups was an effective method for the delivery of Ampyra drug in the living systems.


Functionalized graphene nanosheet Ampyra drug Drug delivery DFT AIM NBO 



The authors thank the Research Council of the Semnan University for support of this study.

Supplementary material

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Supplementary Material 1 (DOCX 2317 kb)


  1. Alghwiri, A.A., Khalil, H., Al-Sharman, A., El-Salem, Kh: Depression is a predictor for balance in people with multiple sclerosis. Mult. Scler. Relat. Disord. 24, 28–31 (2018)CrossRefGoogle Scholar
  2. Biegler-Konig, F.: AIM2000 Designed. University of Applied Sciences, Bielefeld (2001)Google Scholar
  3. Boys, S.F., Bernardi, F.D.: The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys. 19, 553–566 (1970)CrossRefGoogle Scholar
  4. Cho, K., Wang, X.U., Nie, S., Shin, D.M.: Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res. 14, 1310–1316 (2008)CrossRefGoogle Scholar
  5. Dass, C.R., Su, T.: Particle-mediated intravascular delivery of oligonucleotides to tumors: associated biology and lessons from genotherapy. Drug. Deliv. 8, 191–213 (2001)CrossRefGoogle Scholar
  6. Duan, X., Xiao, J., Yin, Q., Zhang, Z., Yu, H., Mao, S., Li, Y.: Smart pH-sensitive and temporal controlled polymeric micelles for effective combination therapy of doxorubicin and disulfiram. ACS Nano 7, 5858–5869 (2013)CrossRefGoogle Scholar
  7. Dubin, C.H.: Special delivery: pharmaceutical companies aim to target their drugs with nano precision. Mech. Eng. Nanotechnol. 126, 10–12 (2004)Google Scholar
  8. Espinosa, E., Molins, E.: Retrieving interaction potentials from the topology of the electron density distribution: the case of hydrogen bonds. J. Chem. Phys. 113, 5686–5694 (2000)CrossRefGoogle Scholar
  9. Espinosa, E., Souhassou, M., Lachekar, H., Lecomte, C.: Topological analysis of the electron density in hydrogen bonds. Acta Crystallogr. Sect. B 55, 563–572 (1999)CrossRefGoogle Scholar
  10. Esrafili, M.: Investigation of H-bonding and halogen bonding effects in dichloroacetic acid: DFT calculations of NQR parameters and QTAIM analysis. J. Mol. Model. 18, 5005–5016 (2012)CrossRefGoogle Scholar
  11. Feng, L.Z., Liu, Z.A.: Graphene in biomedicine: opportunities and challenges. Nanomedicine. 6, 317–324 (2011)CrossRefGoogle Scholar
  12. Feng, L., Wu, L., Qu, X.: New horizons for diagnostics and therapeutic applications of graphene and graphene oxide. Adv. Mater. 25, 168–186 (2013)CrossRefGoogle Scholar
  13. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Montgomery, J.A., Jr. Vreven, T., Kudin, K.N., Burant, J.C., Millam, J.M., Iyengar, S.S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G.A., Nakatsuji, H., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Klene, M., Li, X., Knox, J.E., Hratchian, H.P., Cross, J.B., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Ayala, P.Y., Morokuma, K., Voth, G.A., Salvador, P., Dannenberg, J.J., Zakrzewski, V.G., Dapprich, S., Daniels, A.D., Strain, M.C., Farkas, O., Malick, D.K., Rabuck, A.D., Raghavachari, K., Foresman, J.B., Ortiz, J.V., Cui, Q., Baboul, A.G., Clifford, S., Cioslowski, J., Liu, G., Stefanov, B.B., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R.L., Fox, D.J., Keith, T., Al-Laham, M.A., Peng, C.Y., Nana-yakkara, A., Challacombe, M., Gill, P.M.W., Johnson, B., Chen, W., Wong, M.W., Gonzalez, C., Pople, J.A.: Gaussian 03, Revision C.02 (or D.01). Gaussian Inc., Pittsburgh (2003)Google Scholar
  14. Geim, A.K., Novoselov, K.S.: The rise of graphene. Nat. Mater. 6, 183–191 (2007)CrossRefGoogle Scholar
  15. Ghosh, M., Brahmachari, S., Das, P.K.: pH-responsive single walled carbon nanotube dispersion for target specific release of doxorubicin to cancer cells. Macromol. Biosci. 14, 1795–1806 (2014)CrossRefGoogle Scholar
  16. Glendening, E.D., Reed, A.E., Carpenter, J.E., Weinhold, F.: NBO, Version 3.1. Gaussian Inc., Pittsburgh (1992)Google Scholar
  17. Gonçalves, G., Vila, M., Portoles, M.T., Vallet-Regi, M., Gracio, J., Marques, P.A.A.: Nano-graphene oxide: a potential multifunctional platform for cancer therapy. Adv. Healthc. Mater. 2, 1072–1090 (2013)CrossRefGoogle Scholar
  18. Goodman, A.D., Brown, T.R., Cohen, J.A., Krupp, L.B., Schapiro, R., Schwid, S.R., Cohen, R., Marinucci, L.N., Blight, A.R.: Fampridine MS-F202 study group, dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology. 71, 1134–1141 (2008)CrossRefGoogle Scholar
  19. Hasanzade, Z., Raissi, H.: Solvent/co-solvent effects on the electronic properties and adsorption mechanism of anticancer drug Thioguanine on graphene oxide surface as a nanocarrier: Density functional theory investigation and a molecular dynamics. Appl. Surf. Sci. 422, 1030–1041 (2017)CrossRefGoogle Scholar
  20. He, H., Klinowski, J., Forster, M., Lerf, A.: A new structural model for graphite oxide. Chem. Phys. Lett. 287, 53–56 (1998)CrossRefGoogle Scholar
  21. Kamel, M., Raissi, H., Morsali, A.: Theoretical study of solvent and co-solvent effects on the interaction of Flutamide anticancer drug with Carbon nanotube as a drug delivery system. J. Mol. Liq. 248, 490–500 (2017)CrossRefGoogle Scholar
  22. Kaminskas, L.M., McLeod, V.M., Kelly, B.D., Sberna, G., Boyd, B.J., Williamson, M., Owen, D.J., Porter, C.J.: A comparison of changes to doxorubicin pharmacokinetics, antitumor activity, and toxicity mediated by PEGylated dendrimer and PEGylated liposome drug delivery systems. Nanomedicine 8, 103–111 (2012)CrossRefGoogle Scholar
  23. Ke, X.Y., Ng, V.W., Gao, S.J., Tong, Y.W., Hedrick, J.L., Yang, Y.Y.: Co-delivery of thioridazine and doxorubicin using polymeric micelles for targeting both cancer cells and cancer stem cells. Biomaterials 35, 1096–1108 (2014)CrossRefGoogle Scholar
  24. Khorram, R., Raissi, H., Morsali, A.: Assessment of solvent effects on the interaction of carmustine drug with the pristine and COOH-functionalized single-walled carbon nanotubes: a DFT perspective. J. Mol. Liq. 240, 87–89 (2017)CrossRefGoogle Scholar
  25. Korenke, A.R., Rivey, M.P., Allington, D.R.: Sustained-release fampridine for symptomatic treatment of multiple sclerosis. Ann. Pharmacother. 42(10), 1458–1465 (2008)CrossRefGoogle Scholar
  26. Kuma, M.N.: Nano and microparticles as controlled drug delivery devices. J. Pharm. Pharm. Sci. 3, 234–258 (2000)Google Scholar
  27. Kumar, P.V., Bardhan, N.M., Tongay, S., Wu, J., Belcher, A.M., Grossman, J.C.: Scalable enhancement of graphene oxide properties by thermally driven phase transformation. Nat. Chem. 6, 151–158 (2014)CrossRefGoogle Scholar
  28. Lai, P.S., Lou, P.J., Peng, C.L., Pai, C.L., Yen, W.N., Huang, M.Y., Young, T.H., Shieh, M.J.: Doxorubicin delivery by polyamidoamine dendrimer conjugation and photochemical internalization for cancer therapy. J. Control. Release 122, 39–46 (2007)CrossRefGoogle Scholar
  29. Lee, C., Wei, X., Kysar, J.W., Hone, J.: Measurement of the elastic properties and intrinsic strength of monolayer graphene. Science 321, 385–388 (2008)CrossRefGoogle Scholar
  30. Liu, H., Lee, J.Y.: Electric field effects on the adsorption of CO on a graphene nanodot and the healing mechanism of a vacancy in a graphene nanodot. J. Phys. Chem. C 116, 3034–3041 (2012)CrossRefGoogle Scholar
  31. Liu, Z., Robinson, J.T., Sun, X., Dai, H.: PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J. Am. Chem. Soc. 130, 10876–10877 (2008)CrossRefGoogle Scholar
  32. Liu, Z., Fan, A.C., Rakhra, K., Sherlock, S., Goodwin, A., Chen, X., Yang, Q., Felsher, D.W., Dai, H.: Supramolecular stacking of doxorubicin on carbon nanotubes for in vivo cancer therapy. Angew. Chem. Int. Ed. 48, 7668–7672 (2009)CrossRefGoogle Scholar
  33. Liu, J., Cui, L., Losic, D.: Graphene and graphene oxide as new nanocarriers for drug delivery applications. Acta Biomater. 9, 9243–9257 (2013)CrossRefGoogle Scholar
  34. Mahdavifar, Z., Moridzadeh, R.: Theoretical prediction of encapsulation and adsorption of platinum-anticancer drugs into single walled boron nitride and carbon nanotubes. J. Incl. Phenom. Macrocycl. Chem. 79, 443–457 (2014)CrossRefGoogle Scholar
  35. Malhotra, M., Ghai, P., Narasimhan, B., Deep, A.: Dalfampridine: Review on its recent development for symptomatic improvement in patients with multiple sclerosis. Arab. J. Chem. 9, S1443–S1449 (2016)CrossRefGoogle Scholar
  36. Mennucci, B.: Polarizable continuum model. WIREs. Comput. Mol. Sci. 2, 386–404 (2012)CrossRefGoogle Scholar
  37. Mianehrow, H., Moghadam, M.H., Sharif, F., Mazinani, S.: Graphene-oxide stabilization in electrolyte solutions using hydroxyethyl cellulose for drug delivery application. Int. J. Pharm. 484, 276–282 (2015)CrossRefGoogle Scholar
  38. Miertus, S., Scrocco, E., Tomasi, J.: Electrostatic interaction of solute with a continuum. A direct utilization of ab initio molecular potentials for the prevision of solvent effects. J. Chem. Phys. 55, 117–129 (1981)Google Scholar
  39. Ni, Y., Zhang, F., Kokot, S.: Graphene oxide as a nanocarrier for loading and delivery of medicinal drugs and as a biosensor for detection of serum albumin. Anal. Chim. Acta 769, 40–48 (2013)CrossRefGoogle Scholar
  40. Noseda Grau, E., Roman, G., Diaz Company, A., Brizuela, G., Juan, A., Simonetti, S.: Relevance of silica surface morphology in Ampyra adsorption. Insights from quantum chemical calculations. RSC Adv. 9, 4415 (2019)CrossRefGoogle Scholar
  41. Parr, R.G., Pearson, R.G.: Absolute hardness: companion parameter to absolute electronegativity. J. Am. Chem. Soc. 105, 7512–7516 (1983)CrossRefGoogle Scholar
  42. Parr, R.G., Szentpaly, L.V., Liu, S.: Electrophilicity index. J. Am. Chem. Soc. 121, 1922–1924 (1999)CrossRefGoogle Scholar
  43. Petros, R.A., De Simone, J.M.: Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug. Discov. 9, 615–627 (2010)CrossRefGoogle Scholar
  44. 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)CrossRefGoogle Scholar
  45. Safdari, F., Raissi, H., Shahabi, M., Zaboli, M.: DFT calculations and molecular dynamics simulation study on the adsorption of 5-fluorouracil anticancer drug on graphene oxide nanosheet as a drug delivery vehicle. J. Inorg. Organomet. Polym. 27, 805–817 (2017)CrossRefGoogle Scholar
  46. Saha, S., Roy, R.K., Pal, S.: CDASE–a reliable scheme to explain the reactivity sequence between diels-Alder pairs. Phys. Chem. Chem. Phys. 12, 9328–9338 (2010)CrossRefGoogle Scholar
  47. Shahabi, M., Raissi, H.: Investigation of the molecular structure, electronic properties, AIM, NBO, NMR and NQR parameters for the interaction of Sc, Ga and Mg-doped (6,0) aluminum nitride nanotubes with COCl2 gas by DFT study. J. Incl. Phenom. Macrocycl. Chem. 84, 99–114 (2016a)CrossRefGoogle Scholar
  48. Shahabi, M., Raissi, H.: Molecular dynamics simulation and quantum chemical studies on the investigation of aluminum nitride nanotube as phosgene gas sensor. J. Incl. Phenom. Macrocycl. Chem. 86, 305–322 (2016b)CrossRefGoogle Scholar
  49. Shahabi, M., Raissi, H.: Investigation of the solvent effect, molecular structure, electronic properties and adsorption mechanism of tegafur anticancer drug on graphene nanosheet surface as drug delivery system by molecular dynamics simulation and density functional approach. J. Incl. Phenom. Macrocycl. Chem. 88, 159–169 (2017a)CrossRefGoogle Scholar
  50. Shahabi, M., Raissi, H.: Screening of the structural, topological, and electronic properties of the functionalized graphene nanosheets as potential Tegafur anticancer drug carriers using DFT method. J. Biomol. Struct. Dyn. 36(10), 2517–2529 (2017b)CrossRefGoogle Scholar
  51. Shahabi, M., Raissi, H.: Assessment of solvent effects on the inclusion behavior of pyrazinamide drug into cyclic peptide based nanotubes as novel drug delivery vehicles. J. Mol. Liq. 268, 326–334 (2018)CrossRefGoogle Scholar
  52. Shahabi, M., Raissi, H., Mollania, F.: Electronic structures, intramolecular hydrogen bond interaction, and aromaticity of substituted 4-amino-3-penten-2-one in ground and electronic excited state. Struct. Chem. 26, 491–506 (2015)CrossRefGoogle Scholar
  53. Shen, H., Zhang, L., Liu, M., Zhang, Z.: Biomedical applications of graphene. Theranostics. 2, 283–294 (2012)CrossRefGoogle Scholar
  54. Shojaie, F., Dehghan, M.: Theoretical study of functionalized single-walled carbon nanotube (5, 5) with Mitoxantrone drug. Nanomed. J. 3, 115–126 (2016)Google Scholar
  55. Ta, H.T., Dass, C.R., Larson, I., Choong, P.F., Dunstan, D.E.: A chitosan–dipotassium orthophosphate hydrogel for the delivery of doxorubicin in the treatment of osteosarcoma. Biomaterials 30, 3605–3613 (2009a)CrossRefGoogle Scholar
  56. Ta, H.T., Han, H., Larson, I., Dass, C.R., Dunstan, D.E.: Chitosan-dibasic orthophosphate hydrogel: a potential drug delivery system. Int. J. Pharm. 371, 134–141 (2009b)CrossRefGoogle Scholar
  57. Vail, D.M., Amantea, M.A., Colbern, G.T., Martin, F.J., Hilger, R.A., Working, P.K.: Pegylated liposomal doxorubicin: proof of principle using preclinical animal models and pharmacokinetic studies. Semin. Oncol. 31, 16–35 (2004)CrossRefGoogle Scholar
  58. Vovusha, H., Sanyal, S., Sanyal, B.: Interaction of nucleobases and aromatic amino acids with graphene oxide and graphene flakes. J. Phys. Chem. Lett. 4, 3710–3718 (2013)CrossRefGoogle Scholar
  59. Wang, Y., Li, Z., Wang, J., Li, J., Lin, Y.: Graphene and graphene oxide: biofunctionalization and applications in biotechnology. Trends Biotechnol. 29, 205–212 (2011)CrossRefGoogle Scholar
  60. Wendt, M., Weinhold, F.: NBO View 1.0. Theoretical Chemistry Institute, University of Wisconsin, Madison (2001)Google Scholar
  61. Yanagisawa, H., Tanaka, T., Ishida, Y., Matsue, M., Rukuta, E., Otaniand, S., Oshima, C.: Phonon dispersion curves of a B C 3 honeycomb epitaxial sheet. Phys. Rev. Lett. 93, 177003 (2004)CrossRefGoogle Scholar
  62. Yang, H., Shan, C., Li, F., Han, D., Zhang, Q., Niu, L.: Covalent functionalization of polydisperse chemically-converted graphene sheets with amine-terminated ionic liquid. Chem. Commun. 14, 3880–3882 (2009)CrossRefGoogle Scholar
  63. Yang, K., Feng, L., Shi, X., Liu, Z.: Nano-graphene in biomedicine: theranostic applications. Chem. Soc. Rev. 42, 530–547 (2013)CrossRefGoogle Scholar
  64. Yuan, L., Tang, Q., Yang, D., Zhang, J.Z., Zhang, F., Hu, J.: Preparation of pH-responsive mesoporous silica nanoparticles and their application in controlled drug delivery. J. Phys. Chem. C 115, 9926–9932 (2011)CrossRefGoogle Scholar
  65. Zhao, Y., Truhlar, D.G.: Density functionals with broad applicability in chemistry. Acc. Chem. Res. 41, 157–167 (2008)CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of ChemistrySemnan UniversitySemnanIran
  2. 2.Chemistry DepartmentUniversity of BirjandBirjandIran

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