Skip to main content
SpringerLink
Log in

DFT computational study towards investigating Cladribine anticancer drug adsorption on the graphene and functionalized graphene

  • Original Research
  • Published:
Structural Chemistry Aims and scope Submit manuscript

Abstract

Density functional theory calculations at the M06-2X/6-31G** level have been carried out to examine the adsorption behavior of Cladribine drug on the graphene and graphene nanosheets functionalized with different functional groups in water solution. The influence of molecular orientation on the structural properties, adsorption energies, quantum molecular descriptors, and the equilibrium distances has been investigated for studied nanosheets. Considering the results, the nature of drug adsorption on the surface of nanosheets is physical and it turned out that the adsorption energy of the considered complexes has increased by functionalization of the nanosheet. It is observed that the intermolecular hydrogen bonds between Cladribine and the functionalized graphene nanosheets have an influential role in the stability of the physisorption configurations. The negative values of solvation energies illustrate that the solvation of complexes is a spontaneous process and water stabilizes the considered complexes. The quantum theory of atoms has been also applied to investigate the properties of the bond critical points and illustrate closed shell interactions between the Cladribine drug molecule and the nanosheets. The analysis of natural bond orbital revealed that the Cladribine drug is able to be adsorbed on the surface of nanosheets with a charge transfer from the drug molecule to the nanosheets. Consequently, the functionalized graphene nanosheet with epoxide group has improved the interaction between drug molecules and graphene nanosheet with considerable adsorption energy. Therefore, it is concluded that the modified graphene nanosheets can be used as an appropriate carrier for the Cladribine drug molecule.

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

Similar content being viewed by others

References

  1. Alroughani R, Inshasi JS, Deleu D, Al-Hashel J, Shakra M, Elalamy OR, Shatila AS, Al-Asmi A, Al-Sharoqi I, Canibano BG, Boshra A (2019) An overview of high-efficacy drugs for multiple sclerosis: gulf region expert opinion. Neurol Ther 8(1):13–23

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hiroki M, Masahiro M, Shigeki H, Kojima K, Akiyuki U, Tomohiko U, Ryohei O, Satoshi K (2019) Relapse numbers and earlier intervention by disease modifying drugs are related with progression of less brain atrophy in patients with multiple sclerosis. J Neurol Sci 403:78–84

    Article  Google Scholar 

  3. Gajofatto A, Donata Benedetti M (2015) Treatment strategies for multiple sclerosis: when to start, when to change, when to stop? World J Clin Cases 3(7):545–555

    Article  PubMed  PubMed Central  Google Scholar 

  4. Coyle PK, Reder AT, Freedman MS, Fangd J, Dangond F (2017) Early MRI results and odds of attaining ‘no evidence of disease activity’ status in MS patients treated with interferon β-1a in the EVIDENCE study. Neurol Sci 379:151–156

    Article  CAS  Google Scholar 

  5. Holmoy T, Torkildsen O, Myhr KM (2017) An update on cladribine for relapsing-remitting multiple sclerosis. Expert Opin Pharmacother 18(15):1627–1635

    Article  CAS  PubMed  Google Scholar 

  6. Leist TP, Vermersch P (2007) The potential role for cladribine in the treatment of multiple sclerosis: clinical experience and development of an oral tablet formulation. Curr Med Res Opin 23:2667–2676

    Article  CAS  PubMed  Google Scholar 

  7. Lim EK, Kim T, Paik S, Haam S, Huh YM, Lee K (2014) Nanomaterials for theranostics: recent advances and future challenges. Chem Rev 115:327–394

    Article  CAS  PubMed  Google Scholar 

  8. Domaratzki RE, Ghanem A (2013) Encapsulation and release of cladribine from chitosan nanoparticles. J Appl Polym Sci 128:2173–2179

    CAS  Google Scholar 

  9. Martinez-Rodriguez J, Cadavid D, Wolansky L, Pliner L, Cook (2007) Cladribine in aggressive forms of multiple sclerosis. Eur J Neurol 14:686–689

    Article  CAS  PubMed  Google Scholar 

  10. Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sørensen P, Vermersch P, Chang P, Hamlett A, Musch B, Greenberg SJ (2010) A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med 362(5):416–426

    Article  CAS  PubMed  Google Scholar 

  11. Cook S, Leist T, Comi G, Montalban X, Giovannoni G, Nolting A, Hicking C, Galazka A, Sylvester E (2019) Safety of cladribine tablets in the treatment of patients with multiple sclerosis: an integrated analysis. Mult Scler Relat Disord 29:157–167

    Article  PubMed  Google Scholar 

  12. Langtry HD, Lamb HM (1998) Cladribine: a review of its use in multiple sclerosis. BioDrugs 9:419–433

    Article  CAS  PubMed  Google Scholar 

  13. Betticher D, Fey M, Von Rohr A, Tobler A, Jenzer H, Gratwohl A, Lohri A, Pugin P, Hess U, Pagani O (1994) High incidence of infections after 2-chlorodeoxyadenosine (2-CDA) therapy in patients with malignant lymphomas and chronic and acute leukaemias. Ann Oncol 5:57–64

    Article  CAS  PubMed  Google Scholar 

  14. Dmoszyńska A, Legiec W, Wach M (1999) System using low doses of interleukin 2 in chronic lymphocytic leukemia patients treated with 2-chlorodeoxyadenosine: results of a pilot study. Leuk Lymphoma 34:335–340

    Article  PubMed  Google Scholar 

  15. Vashist SK, Zheng D, Pastorin G et al (2011) Delivery of drugs and biomolecules using carbon nanotubes. Carbon 49:4077–4097

    Article  CAS  Google Scholar 

  16. Siepmann J, Siegel RA, Rathbone MJ (2012) Fundamentals and applications of controlled release drug delivery. Springer, New York

    Book  Google Scholar 

  17. Liu Z, Wang Y, Zhang N (2012) Micelle-like nanoassemblies based on polymer–drug conjugates as an emerging platform for drug delivery. Expert Opin Drug Discovery 9:805–822

    Article  CAS  Google Scholar 

  18. Pahuja P, Arora S, Pawar P (2012) Ocular drug delivery system: a reference to natural polymers. Expert Opin Drug Discovery 9:837–861

    Article  CAS  Google Scholar 

  19. Szűts A, Szabó-Révész P (2012) Sucrose esters as natural surfactants in drug delivery systems-a mini-review. Int J Pharm 433:1–9

    Article  CAS  PubMed  Google Scholar 

  20. Kuma MN (2000) Nano and microparticles as controlled drug delivery devices. J Pharm Pharm Sci 3:234–258

    Google Scholar 

  21. Benita S (2006) Microencapsulation methods and industrial applications. USA CRC Press

  22. Sun X, Feng Z, Hou T et al (2014) Mechanism of graphene oxide as an enzyme inhibitor from molecular dynamics simulations. ACS Appl Mater Interfaces 6:7153–7163

    Article  CAS  PubMed  Google Scholar 

  23. Geim AK, Novoselov KS (2007) The rise of graphene. Nat Mater 6:183–191

    Article  CAS  PubMed  Google Scholar 

  24. Liu F, Ming P, Li J (2007) Ab initio calculation of ideal strength and phonon instability of graphene under tension. Phys Rev B76:064120

    Article  CAS  Google Scholar 

  25. Lee C, Wei X, Kysar JW et al (2008) Measurement of the elasticproperties and intrinsic strength of monolayer graphene. Science 321:385–388

    Article  CAS  PubMed  Google Scholar 

  26. Feng L, Wu L, Qu X (2013) New horizons for diagnostics and therapeutic applications of graphene and graphene oxide. Adv Mater 25:168–186

    Article  CAS  PubMed  Google Scholar 

  27. Gonçalves G, Vila M, Portoles MT, Vallet-Regi M, Gracio J, Marques PAA (2013) Nano-graphene oxide: a potential multifunctional platform for cancer therapy. Adv Healthc Mater 2:1072–1090

    Article  CAS  PubMed  Google Scholar 

  28. Yang K, Feng L, Shi X, Liu Z (2013) Nano-graphene in biomedicine: theranostic applications. Chem Soc Rev 42:530–547

    Article  CAS  PubMed  Google Scholar 

  29. Shen H, Zhang L, Liu M, Zhang Z (2012) Biomedical applications of graphene. Theranostics 2:283–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Feng LZ, Liu ZA (2011) Graphene in biomedicine: opportunities and challenges. Nanomed 6:317–324

    Article  CAS  Google Scholar 

  31. He H, Klinowski J, Forster M et al (1998) A new structural model for graphite oxide. Chem Phys Lett 287:53–56

    Article  CAS  Google Scholar 

  32. Yang HF, Shan CS, Li FH et al (2009) Covalent functionalization of polydisperse chemically-converted graphene sheets with amineterminated ionic liquid. Chem Commun 14:3880–3882

    Article  CAS  Google Scholar 

  33. Liu Z, Robinson JT, Sun X et al (2008) PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc 130:10876–10877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mianehrow H, Moghadam MH, Sharif F, Mazinani S (2015) Graphene-oxide stabilization in electrolyte solutions using hydroxyethyl cellulose for drug delivery application. Int J Pharm 484:276–282

    Article  CAS  PubMed  Google Scholar 

  35. Ni Y, Zhang F, Kokot S (2013) 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

    Article  CAS  PubMed  Google Scholar 

  36. Zhao Y, Truhlar DG (2006) Comparative DFT study of van der Waals complexes: rare-gas dimers, alkaline-earth dimers, zinc dimer, and zinc-rare-gas dimers. J Phys Chem A110:5121–5129

    Article  CAS  Google Scholar 

  37. Zhao Y, Truhlar DG (2008) 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 functionals. Theor Chem Accounts 120:215–241

    Article  CAS  Google Scholar 

  38. Krishnan R, Binkley JS, Seeger R, Pople JA (1980) Self-consistent molecular orbital methods. XX A basis set for correlated wave functions. J Chem Phys 72:650–654

    Article  CAS  Google Scholar 

  39. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalman G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA, Peralta, Jr JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE,Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG,Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009), Gaussian 09, (Revi- a.02); Gaussian Inc, Wallingford CT

  40. Cossi M, Barone V, Mennucci B, Tomasi J (1998) Ab initio study of ionic solutions by a polarizable continuum dielectric model. Chem Phys Lett 286:253–260

    Article  CAS  Google Scholar 

  41. Boys FS, Bernardi F (1970) The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol Phys 19:553–566

    Article  CAS  Google Scholar 

  42. Biegler-Konig F (2001) AIM2000 Designed. University of Applied Sciences, Bielefeld

    Google Scholar 

  43. Glendening ED, Reed AE, Carpenter JE, Weinhold F (1992) NBO, Version 3.1, Gaussian, Inc, Pittsburgh

  44. Shahabi M, Raissi H (2016) 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

    Article  CAS  Google Scholar 

  45. Shahabi M, Raissi H (2016) 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

    Article  CAS  Google Scholar 

  46. Safdari F, Raissi H, Shahabi M, Zaboli M (2017) 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

    Article  CAS  Google Scholar 

  47. Hasanzade Z, Raissi H (2017) 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

    Article  CAS  Google Scholar 

  48. Shahabi M, Raissi H (2017) 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

    Article  CAS  PubMed  Google Scholar 

  49. Shahabi M, Raissi H (2017) 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

    Article  CAS  Google Scholar 

  50. Khorram R, Raissi H, Morsali A (2017) 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

    Article  CAS  Google Scholar 

  51. Dastani N, Arab A, Raissi H (2019) Adsorption of Ampyra anticancer drug on the graphene and functionalized graphene as template materials with high efficient carrier. Adsorption. https://doi.org/10.1007/s10450-019-00142-1

  52. Kame M, Raissi H, Morsali A, Mohammadifard K (2019) Density functional theory study towards investigating the adsorption properties of the γ-Fe2O3 nanoparticles as a nanocarrier for delivery of flutamide anticancer drug. Adsorption. https://doi.org/10.1007/s10450-019-00056-y

  53. Khorram R, Raissi H, Morsali A, Shahabi M (2018) The computational study of the γ-Fe2O3 nanoparticle as carmustine drug delivery system: DFT approach. J Biomol Struct Dyn 37(2):454–464

    Article  CAS  PubMed  Google Scholar 

  54. Espinosa E, Molins E (2000) Retrieving interaction potentials from the topology of the electron density distribution: the case of hydrogen bonds. J Chem Phys 113:5686–5694

    Article  CAS  Google Scholar 

  55. Espinosa E, Souhassou M, Lachekar H, Lecomte C (1999) Topological analysis of the electron density in hydrogen bonds. Acta Crystallogr B 55:563–572

    Article  CAS  PubMed  Google Scholar 

  56. Esrafili MD, Behzadi H (2013) A DFT study on carbon-doping at different sites of (8, 0) boron nitride nanotube. Struct Chem 24:573–581

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  58. Zaboli M, Raissi H (2015) The analysis of electronic structures, adsorption properties, NBO, QTAIM and NMR parameters of the adsorbed hydrogen sulfide on various sites of the outer surface of aluminum phosphide nanotube: a DFT study. Struct Chem 26:1059–1075

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  60. Raissi H, Yoosefian M, Mollania F (2012d) Hydrogen bond studies in substituted imino-acetaldehyde oxime. Comput Theor Chem 996:68–75

    Article  CAS  Google Scholar 

  61. Hokmabady L, Raissi H, Khanmohammadi A (2016) Interactions of the 5-fluorouracil anticancer drug with DNA pyrimidine bases: a detailed computational approach. Struct Chem 27(2):487–504

    Article  CAS  Google Scholar 

  62. Glendening ED, Landis CR, Weinhold F (2012) Natural bond orbital methods. Comput Mol Sci 2:1–42

    Article  CAS  Google Scholar 

  63. Zhiani R (2017) 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

    Article  CAS  Google Scholar 

  64. Kamel M, Raissi H, Morsali A (2017) 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

    Article  CAS  Google Scholar 

  65. Parr RG, Pearson RG (1983) Absolute hardness: companion parameter to absolute electronegativity. J Am Chem Soc 105:7512–7516

    Article  CAS  Google Scholar 

  66. Parr RG, Szentpaly LV, Liu S (1999) Electrophilicity index. J Am Chem Soc 121:1922–1924

    Article  CAS  Google Scholar 

Download references

Funding

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

Author information

Authors and Affiliations

  1. Department of Chemistry, Semnan University, P.O. Box. 35131-19111, Semnan, Iran

    Najme Dastani & Ali Arab

  2. Chemistry Department, University of Birjand, Birjand, Iran

    Heidar Raissi

Authors
  1. Najme Dastani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Arab
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heidar Raissi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali Arab.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 41 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dastani, N., Arab, A. & Raissi, H. DFT computational study towards investigating Cladribine anticancer drug adsorption on the graphene and functionalized graphene. Struct Chem 31, 1691–1705 (2020). https://doi.org/10.1007/s11224-020-01526-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11224-020-01526-8

Keywords

Search

Navigation