Chemical reactivity and adsorption properties of pro-carbazine anti-cancer drug on gallium-doped nanotubes: a quantum chemical study

  • Reza Ghoreishi
  • Majid KiaEmail author
Original Paper


In this study, we propose new armchair single-walled nanotubes (SWNTs) for stable adsorption, increasing drug delivery performance and decreasing side effects of pro-carbazine (Pro-CB) anti-cancer in the framework of B3LYP/6-31 g*/Lanl2DZ level of theory. Indeed, doping gallium (Ga) metal in SWNTs is naturally followed by changing of geometry, increasing dipole moment, and creating one site with high reactivity in order to better adsorption of the drug molecule. Chemical reactivity descriptors show that SWNTs and Pro-CB have electrophile and nucleophile roles in interaction, respectively. More importantly, high local and dual softness in Ga-doped SWNTs indicate improvement of drug adsorption. Parallel and perpendicular complexes result from their interaction in the N and the O sites. Negative values of binding energy (Ebind) show that composed complexes are energetically stable especially in the O site in comparison with the N site. On the other hand, more negative value of the Ebind in SWCNTs shows that these nanotubes are more effective for drug adsorption than their boron nitride counterparts.

Graphical abstract

The Ga dopping results in reducing of HOMO-LUMO gap and increasing charge transfer between SWNTs and Pro-CB, and formation better complex, especially SWCNT.


Pro-carbazine anti-cancer Chemical reactivity descriptors Drug delivery Density of state Natural bond orbital 



In this work, Dr. Fazlolah Eshghi always has helpful hints, a lot of tips and suggestions for our work.

Supplementary material

894_2018_3914_MOESM1_ESM.docx (976 kb)
ESM 1 (DOCX 975 kb)


  1. 1.
    Flahaut E (2011) Carbon nanotubes for biomedical applications. Springer, BerlinGoogle Scholar
  2. 2.
    Lu X, Tian F, Xu X, Wang N, Zhang Q (2003) A theoretical exploration of the 1,3-dipolar cycloadditions onto the sidewalls of (n,n) armchair single-wall carbon nanotubes. J Am Chem Soc 125:10459–10464PubMedCrossRefGoogle Scholar
  3. 3.
    Peles-Lemli B, Kelterer A, Fabian W, Kunsági-Máté S (2010) Noncovalent interaction between aniline and carbon nanotubes: effect of nanotube diameter and the hydrogen-bonded solvent methanol on the adsorption energy and the photophysics. J Phys Chem C 114:5898–5905CrossRefGoogle Scholar
  4. 4.
    Kam NWS, Dai H (2005) Carbon nanotubes as intracellular protein transporters: generality and biological functionality. J Am Chem Soc 127:6021–6026PubMedCrossRefGoogle Scholar
  5. 5.
    Saito R, G. Dresselhaus, M. S. Dresselhaus (1998) Physical properties of carbon nanotubes. World Scientific.
  6. 6.
    Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X, Dai H (2008) Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res 68:6652–6660PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Liu Z, Winters M, Holodniy M, Dai H (2007) siRNA delivery into human T cells and primary cells with carbon nanotube transporters. Angew Chem Int Ed 46:2023–2027CrossRefGoogle Scholar
  8. 8.
    Bhirde A, Gavard J, Zhang G, Sousa A, Masedunskas A (2009) Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. ACS Nano 3:307–316PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Adeli M, Soleyman R, Beiranvand Z, Madani F (2013) Carbon nanotubes in cancer therapy: a more precise look at the role of carbon nanotube–polymer interactions. Chem Soc Rev 42:5231–5256PubMedCrossRefGoogle Scholar
  10. 10.
    Elsaesser A, Howard CV (2012) Toxicology of nanoparticles. Adv Drug Deliv Rev 64:129–137PubMedCrossRefGoogle Scholar
  11. 11.
    Prakash S, Malhotra M, Shao W, Tomaro-Duchesneau C, Abbasi S (2011) Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy. Adv Drug Deliv Rev 63:1340–1351PubMedCrossRefGoogle Scholar
  12. 12.
    Iijima S (1991) Helical microtubules of graphitic carbon. Nature 354:56–58CrossRefGoogle Scholar
  13. 13.
    Vashist SK, Zheng D, Pastorin G, Al-Rubeaan K, Luong JHT, Sheu F-S (2011) Delivery of drugs and biomolecules using carbon nanotubes. Carbon 49:4077–4097CrossRefGoogle Scholar
  14. 14.
    Chen X, Wu P, Rousseas M, Okawa D, Gartner Z, Zettl A (2009) Boron nitride nanotubes are noncytotoxic and can be functionalized for interaction with proteins and cells. J Am Chem Soc 131:890–891PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Rouse JG, Yang J, Barron AR, Monteiro- Riviere N (2006) A fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes. Toxicol in Vitro 20:1313–1320PubMedCrossRefGoogle Scholar
  16. 16.
    Monteiro-Riviere NA, Nemanich RJ, Inman AO, Wang YY, Riviere JE (2005) Multiwalled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 155:377–384PubMedCrossRefGoogle Scholar
  17. 17.
    Shvedova A, Castranova V, Kisin E, Schwegler-Berry D, Murray A, Gandelsman V (2003) Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health A 66:1909–1926Google Scholar
  18. 18.
    Peralta-Inga Z, Lane P, Murray JS, Boyd S, Grice ME, O’Connor CJ, Politzer P (2003) E characterization of surface electrostatic potentials of some (5,5) and (n,1) carbon and boron/nitrogen model nanotubes. Nano 3:21–28Google Scholar
  19. 19.
    Politzer P, Lane P, Murray JS, Concha MC (2003) Comparative analysis of surface electrostatic potentials of carbon, boron/nitrogen and carbon/boron/nitrogen model nanotubes. J Mol Model 11:1–7CrossRefGoogle Scholar
  20. 20.
    Castillo J, Svendsen WE, Rozlosnik N, Escobar P, Martínez F, Castillo-Leon J (2013) Detection of cancer cells using a peptide nanotube–folic acid modified graphene electrode. Analyst 138:1026–1031PubMedCrossRefGoogle Scholar
  21. 21.
    Dhar S, Liu Z, Thomale J, Dai H, Lippard SJ (2008) Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device. J Am Chem Soc 130:11467–11476PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Mavrandonakis A, Farantos SC, Froudakis GE (2006) Glycine interaction with carbon nanotubes: an ab initio study. J Phys Chem B 110:6048–6050PubMedCrossRefGoogle Scholar
  23. 23.
    Zanella I, Fagan SB, Mota R, Fazzio A (2007) Ab initio study of pristine and Si-doped capped carbon nanotubes interacting with nimesulide molecules. Chem Phys Lett 439:348–353CrossRefGoogle Scholar
  24. 24.
    Liu H, Bu Y, Mi Y, Wang Y (2009) Interaction site preference between carbon nanotube and nifedipine: a combined density functional theory and classical molecular dynamics study. J Mol Struct 901:163–168CrossRefGoogle Scholar
  25. 25.
    de Leon A, Jalbout AF, Basiuk VA (2008) SWNT–amino acid interactions: a theoretical study. Chem Phys Lett 457:185–190CrossRefGoogle Scholar
  26. 26.
    Hafizi H, Najafi Chermahini A, Mohammadnezhad G, Teimouri A (2015) A theoretical study on the interaction of amphetamine and single-walled carbon nanotubes. Appl Surf Sci 329:87–93CrossRefGoogle Scholar
  27. 27.
    Raissi H, Mollania F (2014) Immunosuppressive agent leflunomide: a SWNTs-immobilized dihydroortate dehydrogenase inhibitory effect and computational study of its adsorption properties on zigzag single-walled (6,0) carbon and boron nitride nanotubes as controlled drug delivery devices. Eur J Pharm Sci 56:37–54PubMedCrossRefGoogle Scholar
  28. 28.
    Ajima K, Yudasaka M, Murakami T, Maigne A, Shiba K, Ijima S (2005) Carbon nanohorns as anticancer drug carriers. Mol Pharm 2:475–480PubMedCrossRefGoogle Scholar
  29. 29.
    Guven A, Rusakova IA, Lewis MT, Wilson LJ (2012) Cisplatin@US-tube carbon nanocapsules for enhanced chemotherapeutic delivery. Biomaterials 33:1455–1461Google Scholar
  30. 30.
    Dhar S, Daniel WL, Giljohann DA, Mirkin CA, Lippard SJ (2009) Polyvalent oligonucleotide gold nanoparticle conjugates as delivery vehicles for platinum(IV) warheads. J Am Chem Soc 131:14652–14653PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Castillo JJ, Rozo CE, Castillo-Leon J, Rindzevicius T, Svendsen WE, Rozlosnik N, Anja Boisen N, Martinez F (2013) Computational and experimental studies of the interaction between single-walled carbon nanotubes and folic acid. Chem Phys Lett 564:60–64CrossRefGoogle Scholar
  32. 32.
    Shakerzadeh E, Noorizadeh S (2014) A first principles study of pristine and Al-doped boron nitride nanotubes interacting with platinum-based anticancer drugs. Phys E 57:47–55CrossRefGoogle Scholar
  33. 33.
    Karadas N, Ozakan SA (2014) Electrochemical preparation of sodium dodecylsulfate doped over-oxidized polypyrrole/multi-walled carbon nanotube composite on glassy carbon electrode and its application on sensitive and selective determination of anticancer drug: Pemetrexed. Talanta 119:248–254PubMedCrossRefGoogle Scholar
  34. 34.
    Li J, Yoong SL, Goh WJ (2015) In vitro controlled release of cisplatin from gold-carbon nanobottles via cleavable linkages. Int J Nanomedicine 10:7425–7441PubMedPubMedCentralGoogle Scholar
  35. 35.
    Foster J, Weinhold F (1980) Natural hybrid orbitals. J Am Chem Soc 102:7211–7218CrossRefGoogle Scholar
  36. 36.
    M. J. Frisch (2009) In; Wallingford: Gaussian, Inc.Google Scholar
  37. 37.
    McLean A, Chandler G (1980) Contracted Gaussian basis sets for molecular calculations. I. Second row atoms, Z= 11–18. J Chem Phys 72:5639–5648CrossRefGoogle Scholar
  38. 38.
    Tirado-Rives J, Jorgensen WL (2008) Performance of B3LYP density functional methods for a large set of organic molecules. J Chem Theo Comput 4:297–306CrossRefGoogle Scholar
  39. 39.
    Wadt WR, Hay PJ (1985) Ab initio effective core potentials for molecular calculations - potentials for main group elements Na to bi. J Chem Phys 85:284–298CrossRefGoogle Scholar
  40. 40.
    Pakiari AH, Eshghi F (2017) Geometric and electronic structures of vanadium sub-nano clusters, Vn (n = 2-5), and their adsorption complexes with CO and O2 ligands: a DFT-NBO study. Phys Chem Res 5:601–615Google Scholar
  41. 41.
    Parr RG, Yang W (1989) Density-functional theory of atoms and molecules. Oxford University Press, New York Chapter 3 to 5Google Scholar
  42. 42.
    Mulliken RS (1934) A new electroaffinity scale; together with data on valence states and on valence ionization potentials and electron affinities. J Chem Phys 2:782–793CrossRefGoogle Scholar
  43. 43.
    Parr RG (1983) Absolute hardness: companion parameter to absolute electronegativity. J Am Chem Soc 105:7512–7516CrossRefGoogle Scholar
  44. 44.
    Chattaraj PK, Sarkar U, Roy DR (2006) Update 1 of: Electrophilicity index. Chem Rev 106:2065PubMedCrossRefGoogle Scholar
  45. 45.
    Lee C, Yang W, Parr RG (1988) Local softness and chemical reactivity in the molecules CO, SCN H2CO. J Mol Struct 163:305–313CrossRefGoogle Scholar
  46. 46.
    Parthasarathi R, Padmanabhan J, Elango M, Subramanian V, Chattaraj PK (2004) Intermolecular reactivity through the generalized philicity concept. Chem Phys Lett 394:225–230CrossRefGoogle Scholar
  47. 47.
    Padmanabhan J, Parthasarathi R, Subramanian V, Chattaraj PK (2006) Chemical reactivity indices for the complete series of chlorinated benzenes: solvent effect. J Phys Chem A 110:2739–2745PubMedCrossRefGoogle Scholar
  48. 48.
    Reed AE, Weinstock RB, Weinhold F (1998) Natural population analysis. J Chem Phys 83(1985):735–746Google Scholar
  49. 49.
    Gao G, Cagin T, Goddard WA (1998) Energetics, structure, mechanical and vibrational properties of single-walled carbon nanotubes. Nanotec 9:184CrossRefGoogle Scholar
  50. 50.
    Terrones MJ, Romo-Herrera M, Cruz-Silva E, López-Urías F, Muñoz-Sandoval E, Velázquez-Salazar JJ, Terrones H, Bando Y, Golberg D (2007) Pure and doped bonitride nanotubes. Mater Today 10:30–38CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry, Rasht BranchIslamic Azad UniversityRashtIran

Personalised recommendations