Skip to main content
SpringerLink
Log in

DFT and Molecular Simulation Study of Gold Clusters as Effective Drug Delivery Systems for 5-Fluorouracil Anticancer Drug

  • Original Paper
  • Published:
Journal of Cluster Science Aims and scope Submit manuscript

Abstracts

Nowadays, the use of nanomaterials as a delivery system for anticancer drugs is very important. In this paper, first, the electronic and adsorption properties of gold clusters Aun (n = 2–6) interacted 5-Fluorouracil(5FU) molecule were investigated in the gas phase using Density functional theory (DFT) calculation. A Monte Carlo simulation was performed to study their properties in water solution. Gas phase calculation showed higher binding energy for the 5FU/Au4 complex than the others. Thermodynamic analysis indicated the interactions of 5FU and clusters are exothermic, and the drug binding to the Au2 and Au4 is favorable at room temperature. Monte Carlo calculations in aqueous solution showed that odd clusters could act as more suitable candidates for the carrier of 5FU.

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

Similar content being viewed by others

References

  1. D. Pissuwan, T. Niidome, and M. B. Cortie (2011). The forthcoming applications of gold nanoparticles in drug and gene delivery systems. Journal of Controlled Release 149 (1), 65–71.

    Article  CAS  PubMed  Google Scholar 

  2. I. H. El-Sayed, X. Huang, and M. A. El-Sayed (2005). Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: applications in oral cancer. Nano Letters 5 (5), 829–834.

    Article  CAS  PubMed  Google Scholar 

  3. K. Sokolov, M. Follen, J. Aaron, I. Pavlova, A. Malpica, R. Lotan, and R. Richards-Kortum (2003). Real-time vital optical imaging of precancer using anti-epidermal growth factor receptor antibodies conjugated to gold nanoparticles. Cancer Research 63 (9), 1999–2004.

    CAS  PubMed  Google Scholar 

  4. C. J. Murphy, A. M. Gole, J. W. Stone, P. N. Sisco, A. M. Alkilany, E. C. Goldsmith, and S. C. Baxter (2008). Gold nanoparticles in biology: beyond toxicity to cellular imaging. Accounts of Chemical Research 41 (12), 1721–1730.

    Article  CAS  PubMed  Google Scholar 

  5. P. K. Jain, X. Huang, I. H. El-Sayed, and M. A. El-Sayed (2008). Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Accounts of Chemical Research 41 (12), 1578–1586.

    Article  CAS  PubMed  Google Scholar 

  6. E. E. Connor, J. Mwamuka, A. Gole, C. J. Murphy, and M. D. Wyatt (2005). Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1 (3), 325–327.

    Article  CAS  PubMed  Google Scholar 

  7. K. B. Male, B. Lachance, S. Hrapovic, G. Sunahara, and J. H. Luong (2008). Assessment of cytotoxicity of quantum dots and gold nanoparticles using cell-based impedance spectroscopy. Analytical Chemistry 80 (14), 5487–5493.

    Article  CAS  PubMed  Google Scholar 

  8. S. D. Brown, P. Nativo, J.-A. Smith, D. Stirling, P. R. Edwards, B. Venugopal, D. J. Flint, J. A. Plumb, D. Graham, and N. J. Wheate (2010). Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin. Journal of the American Chemical Society 132 (13), 4678–4684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. S. Ketabi and T. Esteshfai (2015). Computer simulation study of the interactions between gold clusters and glutamate in aqueous solution. Journal of Solution Chemistry 44 (10), 2027–2041.

    Article  CAS  Google Scholar 

  10. S. Ketabi, F. Gholipour, and M. Naderi (2022). Molecular simulation study of gold clusters for transporting of thioguanine anticancer drug in aqueous solution. Journal of Cluster Science 33 (1), 135–143.

    Article  CAS  Google Scholar 

  11. E. Kryachko and F. Remacle (2005). Complexes of DNA bases and gold clusters Au3 and Au4 involving nonconventional N− H⊙⊙⊙ Au hydrogen bonding. Nano Letters 5 (4), 735–739.

    Article  CAS  PubMed  Google Scholar 

  12. M. K. Shukla, M. Dubey, E. Zakar, and J. Leszczynski (2009). DFT investigation of the interaction of gold nanoclusters with nucleic acid base guanine and the Watson− Crick guanine-cytosine base pair. The Journal of Physical Chemistry C 113 (10), 3960–3966.

    Article  CAS  Google Scholar 

  13. G. Lv, F. Wei, Q. Li, Q. Shen, H. Jiang, Y. Zhou, and X. Wang (2010). DFT study on the interactions between Au n (n= 2… 4) and adenine. Journal of Nanoscience and Nanotechnology 10 (2), 809–818.

    Article  CAS  PubMed  Google Scholar 

  14. G. Lv, F. Wei, H. Jiang, Y. Zhou, and X. Wang (2009). DFT study on the intermolecular interactions between Aun (n= 2–4) and thymine. Journal of Molecular Structure: THEOCHEM 915 (1–3), 98–104.

    Article  CAS  Google Scholar 

  15. A. Kumar, P. Mishra, and S. Suhai (2006). Binding of gold clusters with DNA base pairs: a density functional study of neutral and anionic GC− Au n and AT− Au n (n= 4, 8) complexes. The Journal of Physical Chemistry A 110 (24), 7719–7727.

    Article  CAS  PubMed  Google Scholar 

  16. J. S. Al-Otaibi, Y. S. Mary, and Y. S. Mary (2022). Adsorption of a thione bioactive derivative over different silver/gold clusters–DFT investigations. Computational and Theoretical Chemistry 1207, 113497.

    Article  Google Scholar 

  17. B. Khodashenas, M. Ardjmand, M. S. Baei, A. S. Rad, and A. A. Khiyavi (2019). Gelatin–gold nanoparticles as an ideal candidate for curcumin drug delivery: experimental and DFT studies. Journal of Inorganic and Organometallic Polymers and Materials 29 (6), 2186–2196.

    Article  CAS  Google Scholar 

  18. Y. Zhou (2008). Nanotubes: a new carrier for drug delivery systems. The Open Nanoscience Journal 2 (1), 1–5.

    Article  CAS  Google Scholar 

  19. J. F. Eliason and A. Megyeri (2004). Potential for predicting toxicity and response of fluoropyrimidines in patients. Current Drug Targets 5 (4), 383–388.

    Article  CAS  PubMed  Google Scholar 

  20. D. B. Longley, D. P. Harkin, and P. G. Johnston (2003). 5-fluorouracil: mechanisms of action and clinical strategies. Nature Reviews Cancer 3 (5), 330–338.

    Article  CAS  PubMed  Google Scholar 

  21. P. Hm and G. Peters (1988). Fluorouracil: biochemistry and pharmacology. Journal of Clinical Oncology 6, 1653–1664.

    Article  Google Scholar 

  22. M. J. Pishvaian, H. Wang, A. R. He, J. J. Hwang, B. G. Smaglo, S. S. Kim, B. A. Weinberg, L. M. Weiner, J. L. Marshall, and J. R. Brody (2020). A phase I/II study of veliparib (ABT-888) in combination with 5-fluorouracil and oxaliplatin in patients with metastatic pancreatic cancer. Clinical Cancer Research 26 (19), 5092–5101.

    Article  CAS  PubMed  Google Scholar 

  23. F. Jubeen, A. Liaqat, F. Amjad, M. Sultan, S. Z. Iqbal, I. Sajid, M. B. Khan Niazi, and F. Sher (2020). Synthesis of 5-fluorouracil cocrystals with novel organic acids as coformers and anticancer evaluation against HCT-116 colorectal cell lines. Crystal Growth & Design 20 (4), 2406–2414.

    Article  CAS  Google Scholar 

  24. A. Yaraghi, O. M. Ozkendir, and M. Mirzaei (2015). DFT studies of 5-fluorouracil tautomers on a silicon graphene nanosheet. Superlattices and Microstructures 85, 784–788.

    Article  CAS  Google Scholar 

  25. E. Entezar-Almahdi, S. Mohammadi-Samani, L. Tayebi, and F. Farjadian (2020). Recent advances in designing 5-fluorouracil delivery systems: a stepping stone in the safe treatment of colorectal cancer. International Journal of Nanomedicine 15, 5445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. S. Javanbakht, A. Hemmati, H. Namazi, and A. Heydari (2020). Carboxymethylcellulose-coated 5-fluorouracil@ MOF-5 nano-hybrid as a bio-nanocomposite carrier for the anticancer oral delivery. International Journal of Biological Macromolecules 155, 876–882.

    Article  CAS  PubMed  Google Scholar 

  27. A. Kouchaki, O. Gülseren, N. Hadipour, and M. Mirzaei (2016). Relaxations of fluorouracil tautomers by decorations of fullerene-like SiCs: DFT studies. Physics Letters A 380 (25–26), 2160–2166.

    Article  CAS  Google Scholar 

  28. K. Nishida, R. Fujiwara, Y. Kodama, S. Fumoto, T. Mukai, M. Nakashima, H. Sasaki, and J. Nakamura (2005). Regional delivery of model compounds and 5-fluorouracil to the liver by their application to the liver surface in rats: its implication for clinical use. Pharmaceutical Research 22 (8), 1331–1337.

    Article  CAS  PubMed  Google Scholar 

  29. K. Chen, J. Chen, M. Guo, Z. Li, and S. Yao (2006). Electrochemical behavior of MCF-7 cells on carbon nanotube modified electrode and application in evaluating the effect of 5-fluorouracil. Electroanalysis: An International Journal Devoted to Fundamental and Practical Aspects of Electroanalysis 18 (12), 1179–1185.

    Article  CAS  Google Scholar 

  30. A. Shah, E. Nosheen, F. Zafar, D. D. Dionysiou, A. Badshah, and G. S. Khan (2012). Photochemistry and electrochemistry of anticancer uracils. Journal of Photochemistry and Photobiology B: Biology 117, 269–277.

    Article  CAS  PubMed  Google Scholar 

  31. A. Soltani, M. T. Baei, E. T. Lemeski, S. Kaveh, and H. Balakheyli (2015). A DFT study of 5-fluorouracil adsorption on the pure and doped BN nanotubes. Journal of Physics and Chemistry of Solids 86, 57–64.

    Article  CAS  Google Scholar 

  32. M. Rahbar, A. Morsali, M. R. Bozorgmehr, and S. A. Beyramabadi (2020). Quantum chemical studies of chitosan nanoparticles as effective drug delivery systems for 5-fluorouracil anticancer drug. Journal of Molecular Liquids 302, 112495.

    Article  CAS  Google Scholar 

  33. A. M. Dhumad, H. J. Majeed, H. Zandi, and K. Harismah (2021). FeC19 cage vehicle for fluorouracil anticancer drug delivery: DFT approach. Journal of Molecular Liquids 333, 115905.

    Article  CAS  Google Scholar 

  34. M. D. Esrafili and A. A. Khan (2022). Alkali metal decorated C 60 fullerenes as promising materials for delivery of the 5-fluorouracil anticancer drug: a DFT approach. RSC Advances 12 (7), 3948–3956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. F. Fayyaz, M. Yar, A. Gulzar, and K. Ayub (2022). First principles calculations of the adsorption of fluorouracil and nitrosourea on CTF-0; organic frameworks as drug delivery systems for cancer treatment. Journal of Molecular Liquids 356, 118941.

    Article  CAS  Google Scholar 

  36. Y. Cao, S. Alamri, A. A. Rajhi, A. E. Anqi, and M. Derakhshandeh (2022). The capability of boron carbide nanotube as a nanocarrier for fluorouracil anticancer drug delivery; DFT study. Materials Chemistry and Physics 275, 125260.

    Article  CAS  Google Scholar 

  37. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, et al. (2009). RA Gaussian09, 1. Gaussian Inc Wallingford CT 121, 150–166.

    Google Scholar 

  38. A. D. Becke (1988). Density-functional exchange-energy approximation with correct asymptotic behavior. Physical Review A 38 (6), 3098.

    Article  CAS  Google Scholar 

  39. L. Ning, S. Jingling, S. Jinhai, L. Laishun, X. Xiaoyu, L. Meihong, and J. Yan (2005). Study on the THz spectrum of methamphetamine. Optics Express 13 (18), 6750–6755.

    Article  PubMed  Google Scholar 

  40. Y. Zhao and D. G. Truhlar (2008). Density functionals with broad applicability in chemistry. Accounts of chemical research 41 (2), 157–167.

    Article  CAS  PubMed  Google Scholar 

  41. K. L. Schuchardt, B. T. Didier, T. Elsethagen, L. Sun, V. Gurumoorthi, J. Chase, J. Li, and T. L. Windus (2007). Basis set exchange: a community database for computational sciences. Journal of Chemical Information and Modeling 47 (3), 1045–1052.

    Article  CAS  PubMed  Google Scholar 

  42. J. Jiang, T. Yan, D. Cui, J. Wang, J. Shen, F. Guo, and Y. Lin (2020). A DFT study on the effect of Au-decoration on the interaction of adrucil drug with BC2N nanotubes in the gas phase and aqueous solution. Journal of Molecular Liquids 315, 113741.

    Article  CAS  Google Scholar 

  43. M. Kurban and İ Muz (2020). Theoretical investigation of the adsorption behaviors of fluorouracil as an anticancer drug on pristine and B-, Al-, Ga-doped C36 nanotube. Journal of Molecular Liquids 309, 113209.

    Article  CAS  Google Scholar 

  44. K. Nejati, A. Hosseinian, E. Vessally, A. Bekhradnia, and L. Edjlali (2017). A comparative DFT study on the interaction of cathinone drug with BN nanotubes, nanocages, and nanosheets. Applied Surface Science 422, 763–768.

    Article  CAS  Google Scholar 

  45. J. Kaur, P. Singla, and N. Goel (2015). Adsorption of oxazole and isoxazole on BNNT surface: a DFT study. Applied Surface Science 328, 632–640.

    Article  CAS  Google Scholar 

  46. Y.-F. Li, A.-J. Mao, Y. Li, and X.-Y. Kuang (2012). Density functional study on size-dependent structures, stabilities, electronic and magnetic properties of Au n M (M= Al and Si, n= 1–9) clusters: comparison with pure gold clusters. Journal of Molecular Modeling 18 (7), 3061–3072.

    Article  CAS  PubMed  Google Scholar 

  47. R. G. Parr, Lv. Szentpály, and S. Liu (1999). Electrophilicity index. Journal of the American Chemical Society 121 (9), 1922–1924.

    Article  CAS  Google Scholar 

  48. N. M. O’boyle, A. L. Tenderholt, and K. M. Langner (2008). Cclib a library for package-independent computational chemistry algorithms. Journal of Computational Chemistry 29 (5), 839–845.

    Article  PubMed  Google Scholar 

  49. N. Metropolis, A. W. Rosenbluth, M. N. Rosenbluth, A. H. Teller, and E. Teller (1953). Equation of state calculations by fast computing machines. The Journal of Chemical Physics 21 (6), 1087–1092.

    Article  CAS  Google Scholar 

  50. S. Ketabi, S. M. Hashemianzadeh, and M. MoghimiWaskasi (2013). Study of DNA base-Li doped SiC nanotubes in aqueous solutions: a computer simulation study. Journal of Molecular Modeling 19 (4), 1605–1615.

    Article  CAS  PubMed  Google Scholar 

  51. H. Hashemi Haeri, S. Ketabi, and S. M. Hashemianzadeh (2012). The solvation study of carbon, silicon and their mixed nanotubes in water solution. Journal of Molecular Modeling 18 (7), 3379–3388.

    Article  CAS  PubMed  Google Scholar 

  52. W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, R. W. Impey, and M. L. Klein (1983). Comparison of simple potential functions for simulating liquid water. The Journal of chemical physics 79 (2), 926–935.

    Article  CAS  Google Scholar 

  53. W. L. Jorgensen (1981). Transferable intermolecular potential functions for water, alcohols, and ethers: application to liquid water. Journal of the American Chemical Society 103 (2), 335.

    Article  CAS  Google Scholar 

  54. J.-P. Hansen and I. R. McDonald (1988). Theory of simple liquids. Physics Today 41 (10), 89–90.

    Article  Google Scholar 

  55. A. K. Rappé, C. J. Casewit, K. Colwell, W. A. Goddard III., and W. M. Skiff (1992). UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. Journal of the American Chemical Society 114 (25), 10024–10035.

    Article  Google Scholar 

  56. J. Pranata, S. G. Wierschke, and W. L. Jorgensen (1991). OPLS potential functions for nucleotide bases: relative association constants of hydrogen-bonded base pairs in chloroform. Journal of the American Chemical Society 113 (8), 2810–2819.

    Article  CAS  Google Scholar 

  57. D. L. Beveridge and F. DiCapua (1989). Free energy via molecular simulation: applications to chemical and biomolecular systems. Annual Review of Biophysics and Biophysical Chemistry 18 (1), 431–492.

    Article  CAS  PubMed  Google Scholar 

  58. A. R. Leach and A. R. Leach, Molecular modelling: principles and applications (Pearson Education, 2001).

    Google Scholar 

  59. X.-B. Li, H.-Y. Wang, X.-D. Yang, Z.-H. Zhu, and Y.-J. Tang (2007). Size dependence of the structures and energetic and electronic properties of gold clusters. The Journal of Chemical Physics 126 (8), 084505.

    Article  PubMed  Google Scholar 

  60. G. Zanti and D. Peeters, Electronic structure analysis of small gold clusters Au m (m≤ 16) by density functional theory, in B. Champagne, M. S. Deleuze, F. De Proft, and T. Leyssens (eds.), Theoretical chemistry in Belgium (Springer, 2014), pp. 261–275.

    Chapter  Google Scholar 

  61. M.-S. Liao, P. Bonifassi, J. Leszczynski, P. C. Ray, M.-J. Huang, and J. D. Watts (2010). Structure, bonding, and linear optical properties of a series of silver and gold nanorod clusters: DFT/TDDFT studies. The Journal of Physical Chemistry A 114 (48), 12701–12708.

    Article  CAS  PubMed  Google Scholar 

  62. H. M. Lee and K. S. Kim (2012). Observable structures of small neutral and anionic gold clusters. Chemistry—A European Journal 18 (41), 13203–13207.

    Article  CAS  PubMed  Google Scholar 

  63. H. Zhang, J. Zhu, H. Zhang, J. Zhang, Y. Zhang, and Z.-H. Lu (2017). The structural, electronic and catalytic properties of Au n (n= 1–4) nanoclusters on monolayer MoS 2. RSC Advances 7 (67), 42529–42540.

    Article  CAS  Google Scholar 

  64. J. Jules and J. R. Lombardi (2003). Transition metal dimer internuclear distances from measured force constants. Journal of Physical Chemistry A 2003, 107.

    Google Scholar 

  65. J. Engel, S. Francis, and A. Roldan (2019). The influence of support materials on the structural and electronic properties of gold nanoparticles–a DFT study. Physical Chemistry Chemical Physics 21 (35), 19011–19025.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Faezeh Ghazali, Sharieh Hosseini & Sepideh Ketabi

Authors
  1. Faezeh Ghazali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharieh Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sepideh Ketabi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sharieh Hosseini.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghazali, F., Hosseini, S. & Ketabi, S. DFT and Molecular Simulation Study of Gold Clusters as Effective Drug Delivery Systems for 5-Fluorouracil Anticancer Drug. J Clust Sci 34, 1499–1509 (2023). https://doi.org/10.1007/s10876-022-02329-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10876-022-02329-z

Keywords

Search

Navigation