Complexation of metal cations (mono-, di- and trivalent) to cucurbiturils: Insights from a DFT/SMD study

  • 1 Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, Sofia, Bulgaria
  • 2 Faculty of Chemistry and Pharmacy, Sofia University “St. Kl. Ohridski”, Sofia, Bulgaria


Recently, supramolecular complexes based on synthetic macrocyclic host molecules have received much attention due to their broad applications as drug delivery carriers, biological and chemical sensors, light-emitting materials, bioimaging agents, etc. Cucurbit[n]urils are cavitands known for their high affinity for various guest molecules, although some aspects of their coordination chemistry remain enigmatic. They are still not tested as metalloenzyme models and not much is known about their metal-binding properties. Furthermore, there is no systematic study on the key factors controlling the processes of metal coordination to these systems. In the
computational study herein, DFT molecular modeling has been employed in order to investigate the interactions of biologically essential mono- (Na+), di- (Mg2+) and some trivalent (La3+, Lu3+) metal cations to cucurbit[n]urils and evaluate the major determinants shaping the process of recognition. The thermodynamic descriptors (Gibbs energies in the gas phase and in a water medium) of the corresponding complexation reactions have been estimated. The results obtained shed light on the mechanism of host–guest recognition and disclose which factors more specifically affect the metal binding process.



  1. M. E. Davis and M. E. Brewster, “Cyclodextrin-based pharmaceutics: Past, present and future,” Nat. Rev. Drug Discov., vol. 3, pp. 1023–1035, 2004.
  2. J. Vicens and V. Böhmer, Calixarenes: a versatile class of macrocyclic compounds. 1991.
  3. Ali Bukhzam and Nabil bader, “Crown Ethers : Their Complexes and Analytical Applications,” J. Appl. Chem., vol. 3, pp. 237–244, 2017.
  4. S. J. Barrow, S. Kasera, M. J. Rowland, J. Del Barrio, and O. A. Scherman, “Cucurbituril-Based Molecular Recognition,” Chem. Rev., vol. 115, pp. 12320–12406, 2015.
  5. J. W. Lee, S. Samal, N. Selvapalam, H. J. Kim, and K. Kim, “Cucurbituril homologues and derivatives: New opportunities in supramolecular chemistry,” Acc. Chem. Res., vol. 36, pp. 621–630, 2003.
  6. A. Day, A. P. Arnold, R. J. Blanch, and B. Snushall, “Controlling factors in the synthesis of cucurbituril and its homologues,” J. Org. Chem., vol. 66, pp. 8094–8100, 2001.
  7. J. Lü, J. X. Lin, M. N. Cao, and R. Cao, “Cucurbituril: A promising organic building block for the design of coordination compounds and beyond,” Coord. Chem. Rev., vol. 257, pp. 1334–1356, 2013.
  8. S. Zhang, L. Grimm, Z. Miskolczy, L. Biczók, F. Biedermann, and W. M. Nau, “Binding affinities of cucurbit[: N] urils with cations,” Chem. Commun., vol. 55, no. 94, pp. 14131–14134, 2019.
  9. N. Kircheva et al., “Complexation of biologically essential (mono- And divalent) metal cations to cucurbiturils: a DFT/SMD evaluation of the key factors governing the host-guest recognition,” RSC Adv., vol. 10, pp. 28139– 28147, Jul. 2020.
  10. I. Z. Koleva et al., “Complexation of trivalent metal cations (Al3+, Ga3+, In3+, La3+, Lu3+) to cucurbiturils: a DFT/SMD evaluation of the key factors governing the host-guest recognition,” Phys. Chem. Chem. Phys., vol. 24, pp. 6274–6281, 2022.
  11. Y. Miyahara, K. Abe, and T. Inazu, “„Molecular‟ molecular sieves: Lid-free decamethylcucurbit[5]uril absorbs and desorbs gases selectively,” Angew. Chemie - Int. Ed., vol. 41, pp. 3020–3023, 2002.
  12. D. Bardelang et al., “Cucurbit[n]urils (n = 5-8): A comprehensive solid state study,” Cryst. Growth Des., vol. 11, pp. 5598–5614, 2011.
  13. L. Cao et al., “Influence of hydrophobic residues on the binding of CB[7] toward diammonium ions of common ammonium⋯ammonium distance,” Org. Biomol. Chem., vol. 13, pp. 6249–6254, 2015.
  14. J. A. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; R, “Gaussian 09,” Gaussian Inc. Wallingford CT, 2009.
  15. “The PyMol Graphics System Version 2.2.3.” Schrödinger, LLC, 2018.

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