pp 1–15 | Cite as

Density functional theory study towards investigating the adsorption properties of the γ-Fe2O3 nanoparticles as a nanocarrier for delivery of Flutamide anticancer drug

  • Maedeh KamelEmail author
  • Heidar Raissi
  • Ali Morsali
  • Kamal Mohammadifard


In this work, we perform density functional theory studies to comprehend the structure and energetics of the interaction of γ-Fe2O3 nanoparticles with Flutamide (FLU) anticancer drug. Quantum mechanics calculations by two methods including B3LYP/6-31G** and M06-2X/6-31G** have been used to obtain the details of energetic, geometric, and electronic features of the drug molecule interacting with the surface of the maghemite nanoparticles in water solution. The obtained calculations of M06-2X/6-31G** method approved the observation of the strongest adsorption within the hydrogen bond interactions between two considered molecules are predominate, while the adsorption process of drug on the nanoparticles in B3LYP/6-31G** method is endothermic and hence, the adsorbed structures are unstable. The quantum theory of atoms in molecules analysis illustrates closed shell interactions between the drug molecule and the γ-Fe2O3 nanoparticles. The natural bond orbital analysis demonstrated that the drug molecule has the ability to be adsorbed on the nanoparticle surface with the transfer of charge from the drug molecule to maghemite nanoparticles. Moreover, quantum mechanical descriptors within the drug-nanoparticles systems were investigated and it was implied that binding of FLU molecule with γ-Fe2O3 nanoparticles is thermodynamically favorable. Therefore, γ-Fe2O3 nanoparticles can be introduced as efficient systems for the delivery of the drug molecule.


Flutamide molecule γ-Fe2O3 nanoparticles QTAIM NBO Drug delivery system 


Supplementary material

10450_2019_56_MOESM1_ESM.pdf (207 kb)
Supplementary material 1 (PDF 206 KB)


  1. Akcora, P., Zhang, X., Varughese, B., Briber, R.M., Kofinas, P.: Structural and magnetic characterization of norbornene–deuterated norbornene dicarboxylic acid diblock copolymers doped with iron oxide nanoparticles. Polymer. 46, 5194–5201 (2005)CrossRefGoogle Scholar
  2. Atanasov, M.: Theoretical studies on the higher oxidation states of iron. Inorg. Chem. 38, 4942–4948 (1999)CrossRefGoogle Scholar
  3. Bader, R.F.W.: Atoms in Molecules: A Quantum Theory. Oxford University Press, New York (1990)Google Scholar
  4. Biegler-König, F.: AIM2000. University of Applied Sciences, Bielefeld (2000)Google Scholar
  5. 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
  6. Choe, S.J.: Comparison of different theory models and basis sets in calculations of TPOP24N-oxide geometry and geometries of meso-tetraphenyl chlorin N-oxide regioisomers. Bull. Korean Chem. Soc. 33, 2861–2866 (2012)CrossRefGoogle Scholar
  7. Contreras-Garcia, J., Johnson, E.R., Keinan, S., Chaudret, R., Piquemal, J.P., Beratan, D.N., Yang, W.: NCIPLOT: a program for plotting non-covalent interaction regions. J. Chem. Theory. Comput. 7, 625–632 (2011)CrossRefGoogle Scholar
  8. Corr, S., Gun’ko, Y.K., Douvalis, A., Venkatesan, M., Gunning, R., Nellist, P.: From nanocrystals to nanorods: new iron oxide-silica nanocomposites from metallorganic precursors. J. Phys. Chem. C 112, 1008–1018 (2008)CrossRefGoogle Scholar
  9. Cossi, M., Barone, V., Mennucci, B., Tomasi, J.: Ab initio study of ionic solutions by a polarizable continuum dielectric model. Chem. Phys. Lett. 286, 253–260 (1998)CrossRefGoogle Scholar
  10. El Khoury, J.M., Caruntu, D., O’Connor, C.J., Jeong, K.U., Cheng, S.Z.D., Hu, J.: Poly (allylamine) Stabilized Iron Oxide Magnetic Nanoparticles. J. Nanopart. Res. 9, 959–964 (2007)CrossRefGoogle Scholar
  11. Espinosa, E., Molins, E.: Retrieving interaction potentials from the topology of the electron density distribution: the case of hydrogen bonds. J. Phys. Chem. 113, 5686–5694 (2000)CrossRefGoogle Scholar
  12. Espionsa, E., Souhassou, M., Lachekar, H., Lecomte, C.: Topological analysis of the electron density in hydrogen bonds. Acta. Cryst. B 55, 563–572 (1999)CrossRefGoogle Scholar
  13. Firme, C.P., Bandaru, P.R.: Toxicity issues in the application of carbon nanotubes to biological systems. Nanomedicine 6, 245–256 (2010)CrossRefGoogle Scholar
  14. 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.: Gaussian 03, Revision C, 02. Gaussian Inc., Wallingford (2004)Google Scholar
  15. Fu, L., Dravid, V.P., Klug, K., Liu, X., Mirkin, C.A.: Synthesis and patterning of magnetic nanostructures. Eur. Cell. Mater. 3, 156–157 (2002)Google Scholar
  16. Gharib, A., Morsali, A., Beyramabadi, S., Chegini, H., Ardabili, M.N.: Quantum mechanical study on the rate determining steps of the reaction between 2-aminopyrimidine with dichloro-[1-methyl-2-(naphthylazo) imidazole] palladium (II) complex. Prog. React. Kinet. Mech. 39, 354–364 (2014)CrossRefGoogle Scholar
  17. Glendening, E.D., Reed, A.E., Carpenter, J.E., Weinhold, F.: NBO, Version 3.1, Gaussian, Inc. Pittsburgh (1992)Google Scholar
  18. Glendening, E.D., Landis, C.R., Weinhold, F.: Natural bond orbital methods. Comput. Mol. Sci. 2, 1–42 (2012)CrossRefGoogle Scholar
  19. Gupta, A.K., Gupta, M.: Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26, 3995–4021 (2005)CrossRefGoogle Scholar
  20. 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 dynamic. Appl. Surf. Sci. 422, 1030–1041 (2017)CrossRefGoogle Scholar
  21. Hashemzadeh, H., Raissi, H.: Covalent organic framework as smart and high efficient carrier for anticancer drug delivery: a DFT calculations and molecular dynamics simulation study. J. Phys. D (2018). Google Scholar
  22. Ivanova, E.P., Papiernik, M., Oliveira, A., Sbarski, I., Smekal, T., Grodzinski, P., Nicolau, D.V.: Feasibility of using carboxylic-rich polymeric surfaces for the covalent binding of oligonucleotides for microPCR applications. Smart. Mater. Struct. 11, 783 (2002)CrossRefGoogle Scholar
  23. Jayarathne, L., Ng, W., Bandara, A., Vitanage, M., Dissanayake, C., Weerasooriya, R.: Fabrication of succinic acid- γ-Fe2O3 nano core–shells. Colloids. Surf. A. 403, 96–102 (2012)CrossRefGoogle Scholar
  24. Johnson, E.R., Keinan, S., Mori-Sanchez, P., Contreras-Garcia, J., Cohen, A.J., Yang, W.: Revealing noncovalent interactions. J. Am. Chem. Soc. 132, 6498–6506 (2010)CrossRefGoogle Scholar
  25. 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
  26. Kamel, M., Raissi, H., Morsali, A., Shahabi, M.: Assessment of the adsorption mechanism of Flutamide anticancer drug on the functionalized single-walled carbon nanotube surface as a drug delivery vehicle: An alternative theoretical approach based on DFT and MD. Appl. Surf. Sci. 434, 492–503 (2018)CrossRefGoogle Scholar
  27. 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)CrossRefGoogle Scholar
  28. Kubicki, J.D., Paul, K.W., Sparks, D.L.: Periodic density functional theory calculations of bulk and the (010) surface of goethite. Geochem. Trans. 9, 4 (2008)CrossRefGoogle Scholar
  29. Labrie, F.: Mechanism of action and pure antiandrogenic properties of flutamide. Cancer 72, 3816–3827 (1993)CrossRefGoogle Scholar
  30. Lalley, J., Han, J., Li, C., Dionysiou, X., Nadagouda, D.D.: Phosphate adsorption using modified iron oxide-based sorbents in lake water: kinetics, equilibrium, and column tests. Chem. Eng. J. 284, 1386–1396 (2016)CrossRefGoogle Scholar
  31. Lari, H., Morsali, A., Heravi, M.: Quantum mechanical study of γ-Fe2O3 nanoparticle as a nanocarrier for anticancer drug delivery. Z. Phys. Chem. 232, 579–592 (2018)Google Scholar
  32. Leone, V.O., Pereira, M.C., Aquino, S.F., Oliveira, L.C.A., Correa, S., Ramalho, T.C., Gurgel, L.V.A., Silva, A.C.: Adsorption of diclofenac on a magnetic adsorbent based on maghemite: experimental and theoretical studies. New. J. Chem. 42, 437–449 (2018)CrossRefGoogle Scholar
  33. Lu, T., Chen, F.: Multiwfn: a multifunctional wavefunction analyzer. J. Comput. Chem. 33, 580–592 (2012)CrossRefGoogle Scholar
  34. Mirhaji, E., Yoosefian, M.: Structural analysis, solvent effects and intramolecular interactions in rilpivirine: a new non-nucleoside reverse transcriptase inhibitor for HIV treatment. J. Mol. Liq. 246, 124–130 (2017)CrossRefGoogle Scholar
  35. Morsali, A., Hoseinzade, F., Akbari, A., Beyramabadi, S.A., Ghiasi, R.: Theoretical study of solvent effects on the Cis-to-trans isomerization of [Pd(C6Cl2F3)I(PH3)2]. J. Solution Chem. 42, 1902–1911 (2013)CrossRefGoogle Scholar
  36. Murray, J.S., Sen, K.: Molecular electrostatic potentials, Volume 3, 1st Edition (1996)Google Scholar
  37. Parr, R.G., Pearson, R.G.: Absolute hardness: companion parameter to absolute electronegativity. J. Am. Chem. Soc. 105, 7512–7516 (1983)CrossRefGoogle Scholar
  38. Parr, R.G., Szentpaly, L.V., Liu, S.: Electrophilicity index. J. Am. Chem. Soc. 121, 1922–1924 (1999)CrossRefGoogle Scholar
  39. Pearson, R.G.: Absolute electronegativity and absolute hardness of Lewis acids and bases. J. Am. Chem. Soc. 107, 6801–6806 (1985)CrossRefGoogle Scholar
  40. Popelier, P.L.A.: Characterization of a dihydrogen bond on the basis of the electron density. J. Phys. Chem. A 102, 1873–1878 (1998)CrossRefGoogle Scholar
  41. Raissi, H., Jalbout, A.F., Fazli, M., Yoosefian, M., Ghiassi, H., Wang, Z., De Leon, A.: Intramolecular hydrogen bonding in derivatives of 3-Amino-propenethial. Int. J. Quantum. Chem. 109, 1497–1504 (2009)CrossRefGoogle Scholar
  42. Raissi, H., Jalbout, A.F., Yoosefian, M., Fazli, M., Nowroozi, A., Shahinin, M., De Leon, A.: Intramolecular hydrogen bonding in structural conformers of 2-amino methylene malonaldehyde: AIM and NBO studies. Int. J. Quantum. Chem. 110, 821–830 (2010)Google Scholar
  43. Raissi, H., Farzad, F., Nadim, E.S., Yoosefian, M., Farsi, H., Nowroozi, A., Loghmaninejad, D.: Theoretical study of the effects of substitution, solvation, and structure on the interaction between nitriles and methanol. Int. J. Quantum. Chem. 112, 1273–1284 (2012a)CrossRefGoogle Scholar
  44. Raissi, H., Yoosefian, M., Hajizadeh, A., shakhs Imampour, J., Karimi, M., Farzad, F.: Theoretical Description of Substituent Effects in 2,4-Pentanedione: AIM, NBO, and NMR Study. Bull. Chem. Soc. Jpn 85, 87–92 (2012b)CrossRefGoogle Scholar
  45. Raissi, H., Yoosefian, M., Khoshkhou, S.: Conformational study of the (z)-[(2-iminoethylidone)silyl]amine at the MP2, DFT and G2MP2 levels. Comput. Theor. Chem 983, 1–6 (2012c)CrossRefGoogle Scholar
  46. Raissi, H., Yoosefian, M., Mollania, F.: Hydrogen bond studies in substituted imino-acetaldehyde oxime. Comput. Theor. Chem. 996, 68–75 (2012d)CrossRefGoogle Scholar
  47. Rameev, B.Z., Gupta, A., Anguelouch, A., Xiao, G., Yildiz, F., Tagirov, L.R., Aktas, B.: Probing magnetic anisotropies in half-metallic CrO2epitaxial films by FMR. J. Magn. Magn. Mater. 272–276, 1167–1168 (2004)CrossRefGoogle Scholar
  48. Shao, H., Min, C., Issadore, D., Liong, M., Yoon, T.J., Weissleder, R., Lee, H.: Magnetic nanoparticles and micro NMR for diagnostic applications. Theranostics 2, 55–65 (2012)CrossRefGoogle Scholar
  49. Sohn, B.H., Cohen, R.E., Papaefthymiou, G.C.: Magnetic properties of iron oxide nanoclusters within microdomains of block copolymers. J. Magn. Magn. Mater. 182, 216–224 (1998)CrossRefGoogle Scholar
  50. Venkataramanan, N.S., Suvitha, A., Kawazoe, Y.: Intermolecular interaction in nucleobases and dimethyl sulfoxide/water molecules: a DFT, NBO, AIM and NCI analysis. J. Mol. Graph. Model. 78, 48–60 (2017)CrossRefGoogle Scholar
  51. Wadt, W.R., Hay, P.J.: Ab initio effective core potentials for molecular calculations. Potentials for the transition metal atoms Sc to Hg. J. Phys. Chem. 82, 299–310 (1985)CrossRefGoogle Scholar
  52. Watanabe, H., Seto, J.: The intrinsic equilibrium constants of the surface hydroxyl groups of maghemite and hematite. Bull. Chem. Soc. Jpn 63, 2916–2921 (1990)CrossRefGoogle Scholar
  53. Xie, J., Huang, J., Li, X., Sun, S., Chen, X.: Iron oxide nanoparticle platform for biomedical applications. Curr. Med. Chem. 16, 1278–1294 (2009)CrossRefGoogle Scholar
  54. Xie, J., Liu, G., Eden, H.S., Ai, H., Chen, X.: Surface-engineered magnetic nanoparticle platforms for cancer imaging and therapy. Acc. Chem. Res. 44, 883–892 (2011)CrossRefGoogle Scholar
  55. Yamaura, M., Camilo, R.L., Sampaio, L.C., Macedo, M.A., Nakamura, M., Toma, H.E.: Preparation and characterization of (3-aminopropyl) triethoxysilane-coated magnetite nanoparticles. J. Magn. Magn. Mater. 279, 210–217 (2004)CrossRefGoogle Scholar
  56. Yildiz, D., Bozkaya, U.: Assessment of the extended Koopmans’ theorem for the chemical reactivity: accurate computations of chemical potentials, chemical hardnesses, and electrophilicity indices. J. Comput. Chem. 37, 345–353 (2016)CrossRefGoogle Scholar
  57. Yin, S., Ma, X., Ellis, D.E.: Initial stages of H2O adsorption and hydroxylation of Fe-terminated α-Fe2O3(0 0 0 1) surface. Surf. Sci 601, 2426–2437 (2007)CrossRefGoogle Scholar
  58. Yoosefian, M.: A high efficient nanostructured filter based on functionalized carbon nanotube to reduce the tobacco-specific nitrosamines. NNK. Appl. Surf. Sci. 434, 134–141 (2018)CrossRefGoogle Scholar
  59. Yoosefian, M., Etminan, N.: The role of solvent polarity in the electronic properties, stability and reactivity trend of a tryptophane/Pd doped SWCNT novel nanobiosensor from polar protic to non-polar solvents. RSC Adv. 6, 64818–64825 (2016)CrossRefGoogle Scholar
  60. Yoosefian,M.,Mola,A.: Solvent effects on binding energy, stability order and hydrogen bonding of guanine–cytosine base pair. J. Mol. Liq. 209,526–530(2015).CrossRefGoogle Scholar
  61. Yoosefian, M., Jafari Chermahini, Z., Raissi, H., Mola, A., Sadeghi, M.: A theoretical study on the structure of 2-amino-1,3,4-thiadiazole and its 5-substituted derivatives in the gas phase, water, THF and DMSO solutions. J. Mol. Liq. 203, 137–142 (2015)CrossRefGoogle Scholar
  62. Yoosefian, M., Etminan, N., Ahmadzadeh, S.: Solvents effect on the stability and reactivity of Tamoxifen and its nano metabolites as the breast anticancer drug. J. Mol. Liq. 223, 1151–1157 (2016)CrossRefGoogle Scholar
  63. Yu, M.K., Jeong, Y.Y., Park, J., Park, S., Kim, J.W., Min, J.J., Kim, K., Jon, S.: Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo. Angew. Chem. Int. Ed. 47, 5362–5365 (2008)CrossRefGoogle Scholar
  64. Zhang, Y., He, H., Dong, K., Fan, M., Zhang, S.: A DFT study on lignin dissolution in imidazolium based ionic liquids. RSC Adv. 7, 12670–12681 (2017)CrossRefGoogle Scholar
  65. Zhao, H., Liu, X., Cao, Z., Zhan, Y., Shi, X., Yang, Y., Zhou, J., Xu, J.: Adsorption behavior and mechanism of chloramphenicols, sulfonamides, and non-antibiotic pharmaceuticals on multi-walled carbon nanotubes. J. Hazard. Mater. 310, 235–245 (2016)CrossRefGoogle Scholar
  66. Zhiani, R.: Adsorption of various types of amino acids on the graphene and boron-nitride nano-sheet, a DFT-D3 study. Appl. Surf. Sci. 409, 35–44 (2017)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Maedeh Kamel
    • 1
    Email author
  • Heidar Raissi
    • 2
  • Ali Morsali
    • 3
  • Kamal Mohammadifard
    • 4
  1. 1.Department of ChemistryPayame Noor UniversityTehranIran
  2. 2.Department of ChemistryUniversity of BirjandBirjandIran
  3. 3.Department of Chemistry, Mashhad BranchIslamic Azad UniversityMashhadIran
  4. 4.Department of Chemical EngineeringFerdowsi University of MashhadMashhadIran

Personalised recommendations