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Controlled release from cucurbituril

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Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

The unique pumpkin-shape macrocyclic structure with inherent cavities renders cucurbituril (CB) a type of versatile supramolecular container. On account of their good biocompatibility and low toxicity, the applications of CB to encapsulate drug molecules provide promising candidates and the pharmacological activities have been investigated currently. How to control over the uptake and release of the guest at will is significant for practical applications of drug delivery. The noncovalent nature of supramolecular interactions offers variety of options to control the release of guest molecules from CB under external stimuli, including pH, temperature, metal cations, competing guests, light, redox and so on. Moreover, CB containers are capable of assembling into higher ordered supramolecular structures such as polymers, nanoparticles, hydrogels, and colloids, which greatly enrich the scope of CB-type inclusion materials. Those results provide useful principles and guidelines for controlled release from supramolecular containers.

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References

  1. Cram, D.J.: Molecular container compounds. Nature 356, 29–36 (1992)

    Article  CAS  Google Scholar 

  2. Kang, J.M., Rebek, J.: Entropically driven binding in a self-assembling molecular capsule. Nature 382, 239–241 (1996)

    Article  CAS  Google Scholar 

  3. Martin, T., Obst, U., Rebek, J.: Molecular assembly and encapsulation directed by hydrogen-bonding preferences and the filling of space. Science. 281, 1842–1845 (1998)

    Article  CAS  Google Scholar 

  4. Lehn, J.M.: Perspectives in supramolecular chemistry—from molecular recognition towards molecular information-processing and self-organization. Angew. Chem. Int. Ed. 29, 1304–1319 (1990)

    Article  Google Scholar 

  5. Cram, D.J., Karbach, S., Kim, Y.H., Baczynskyj, L., Kalleymeyn, G.W.: Shell closure of 2 cavitands forms carcerand complexes with components of the medium as permanent guests. J. Am. Chem. Soc. 107, 2575–2576 (1985)

    Article  CAS  Google Scholar 

  6. Wyler, R., Demendoza, J., Rebek, J.: A synthetic cavity assembles through self-complementary hydrogen-bonds. Angew. Chem. Int. Ed. 32, 1699–1701 (1993)

    Article  Google Scholar 

  7. Gibb, C.L.D., Gibb, B.C.: Templated assembly of water-soluble nano-capsules: inter-phase sequestration, storage, and separation of hydrocarbon gases. J. Am. Chem. Soc. 128, 16498–16499 (2006)

    Article  CAS  Google Scholar 

  8. Freeman, W.A., Mock, W.L., Shih, N.Y.: Cucurbituril. J. Am. Chem. Soc. 103, 7367–7368 (1981)

    Article  CAS  Google Scholar 

  9. Kim, J., Jung, I.S., Kim, S.Y., Lee, E., Kang, J.K., Sakamoto, S., Yamaguchi, K., Kim, K.: New cucurbituril homologues: syntheses, isolation, characterization, and X-ray crystal structures of cucurbit[n]uril (n = 5, 7, and 8). J. Am. Chem. Soc. 122, 540–541 (2000)

    Article  CAS  Google Scholar 

  10. Day, A., Arnold, A.P., Blanch, R.J., Snushall, B.: Controlling factors in the synthesis of cucurbituril and its homologues. J. Org. Chem. 66, 8094–8100 (2001)

    Article  CAS  Google Scholar 

  11. Jon, S.Y., Selvapalam, N., Oh, D.H., Kang, J.K., Kim, S.Y., Jeon, Y.J., Lee, J.W., Kim, K.: Facile synthesis of cucurbit[n]uril derivatives via direct functionalization: expanding utilization of cucurbit[n]uril. J. Am. Chem. Soc. 125, 10186–10187 (2003)

    Article  CAS  Google Scholar 

  12. Liu, S.M., Zavalij, P.Y., Isaacs, L.: Cucurbit[10]uril. J. Am. Chem. Soc. 127, 16798–16799 (2005)

    Article  CAS  Google Scholar 

  13. Cheng, X.J., Liang, L.L., Chen, K., Ji, N.N., Xiao, X., Zhang, J.X., Zhang, Y.Q., Xue, S.F., Zhu, Q.J., Ni, X.L., Tao, Z.: Twisted cucurbit[14]uril. Angew. Chem. Int. Ed. 52, 7252–7255 (2013)

    Article  CAS  Google Scholar 

  14. Lagona, J., Mukhopadhyay, P., Chakrabarti, S., Isaacs, L.: The cucurbit[n]uril family. Angew. Chem. Int. Ed. 44, 4844–4870 (2005)

    Article  CAS  Google Scholar 

  15. Masson, E., Ling, X.X., Joseph, R., Kyeremeh-Mensah, L., Lu, X.Y.: Cucurbituril chemistry: a tale of supramolecular success. RSC Adv. 2, 1213–1247 (2012)

    Article  CAS  Google Scholar 

  16. Lee, J.W., Samal, S., Selvapalam, N., Kim, H.J., Kim, K.: Cucurbituril homologues and derivatives: new opportunities in supramolecular chemistry. Acc. Chem. Res. 36, 621–630 (2003)

    Article  CAS  Google Scholar 

  17. Dsouza, R.N., Pischel, U., Nau, W.M.: Fluorescent dyes and their supramolecular host/guest complexes with macrocycles in aqueous solution. Chem. Rev. 111, 7941–7980 (2011)

    Article  CAS  Google Scholar 

  18. Ni, X.L., Xiao, X., Cong, H., Liang, L.L., Cheng, K., Cheng, X.J., Ji, N.N., Zhu, Q.J., Xue, S.F., Tao, Z.: Cucurbit[n]uril-based coordination chemistry: from simple coordination complexes to novel poly-dimensional coordination polymers. Chem. Soc. Rev. 42, 9480–9508 (2013)

    Article  CAS  Google Scholar 

  19. Lu, J., Lin, J.X., Cao, M.N., Cao, R.: Cucurbituril: a promising organic building block for the design of coordination compounds and beyond. Coord. Chem. Rev. 257, 1334–1356 (2013)

    Article  CAS  Google Scholar 

  20. Barrow, S.J., Kasera, S., Rowland, M.J., del Barrio, J., Scherman, O.A.: Cucurbituril-based molecular recognition. Chem. Rev. 115, 12320–12406 (2015)

    Article  CAS  Google Scholar 

  21. Hettiarachchi, G., Nguyen, D., Wu, J., Lucas, D., Ma, D., Isaacs, L., Briken, V.: Toxicology and drug delivery by cucurbit[n]uril type molecular containers. PLoS ONE 5, e10514 (2010)

    Article  Google Scholar 

  22. Uzunova, V.D., Cullinane, C., Brix, K., Nau, W.M., Day, A.I.: Toxicity of cucurbit[7]uril and cucurbit[8]uril: an exploratory in vitro and in vivo study. Org. Biomol. Chem. 8, 2037–2042 (2010)

    Article  CAS  Google Scholar 

  23. Wheate, N.J., Day, A.I., Blanch, R.J., Arnold, A.P., Cullinane, C., Collins, J.G.: Multi-nuclear platinum complexes encapsulated in cucurbit[n]uril as an approach to reduce toxicity in cancer treatment. Chem. Commun. 12, 1424–1425 (2004)

    Article  Google Scholar 

  24. Jeon, Y.J., Kim, S.Y., Ko, Y.H., Sakamoto, S., Yamaguchi, K., Kim, K.: Novel molecular drug carrier: encapsulation of oxaliplatin in cucurbit[7]uril and its effects on stability and reactivity of the drug. Org. Biomol. Chem. 3, 2122–2125 (2005)

    Article  CAS  Google Scholar 

  25. Koner, A.L., Ghosh, I., Saleh, N., Nau, W.M.: Supramolecular encapsulation of benzimidazole-derived drugs by cucurbit[7]uril. Can. J. Chem. 89, 139–147 (2011)

    Article  CAS  Google Scholar 

  26. Ghosh, I., Nau, W.M.: The strategic use of supramolecular pKa shifts to enhance the bioavailability of drugs. Adv. Drug Deliv. Rev. 64, 764–783 (2012)

    Article  CAS  Google Scholar 

  27. Ma, D., Hettiarachchi, G., Nguyen, D., Zhang, B., Wittenberg, J.B., Zavalij, P.Y., Briken, V., Isaacs, L.: Acyclic cucurbit[n]uril molecular containers enhance the solubility and bioactivity of poorly soluble pharmaceuticals. Nat. Chem. 4, 503–510 (2012)

    Article  CAS  Google Scholar 

  28. Jeon, Y.M., Kim, H., Whang, D., Kim, K.: Molecular container assembly capable of controlling binding and release of its guest molecules: reversible encapsulation of organic molecules in sodium ion complexed cucurbituril. J. Am. Chem. Soc. 118, 9790–9791 (1996)

    Article  CAS  Google Scholar 

  29. Liu, L., Nouvel, N., Scherman, O.A.: Controlled catch and release of small molecules with cucurbit[6]uril via a kinetic trap. Chem. Commun. 22, 3243–3245 (2009)

    Article  Google Scholar 

  30. Kim, H.J., Heo, J., Jeon, W.S., Lee, E., Kim, J., Sakamoto, S., Yamaguchi, K., Kim, K.: Selective inclusion of a hetero-guest pair in a molecular host: formation of stable charge-transfer complexes in cucurbit[8]uril. Angew. Chem. Int. Ed. 40, 1526–1529 (2001)

    Article  CAS  Google Scholar 

  31. Ghale, G., Nau, W.M.: Dynamically analyte-responsive macrocyclic host-fluorophore systems. Acc. Chem. Res. 47, 2150–2159 (2014)

    Article  CAS  Google Scholar 

  32. Pemberton, B.C., Raghunathan, R., Volla, S., Sivaguru, J.: From containers to catalysts: supramolecular catalysis within cucurbiturils. Chem.-Eur. J. 18, 12178–12190 (2012)

    Article  CAS  Google Scholar 

  33. Whang, D., Heo, J., Park, J.H., Kim, K.: A molecular bowl with metal ion as bottom: reversible inclusion of organic molecules in cesium ion complexed cucurbituril. Angew. Chem. Int. Ed. 37, 78–80 (1998)

    Article  CAS  Google Scholar 

  34. El Haouaj, M., Ko, Y.H., Luhmer, M., Kim, K., Bartik, K.: NMR investigation of the complexation of neutral guests by cucurbituril. J. Chem. Soc. Perkin Trans. 2, 2104–2107 (2001)

    Article  Google Scholar 

  35. Liu, L., Zhao, N., Scherman, O.A.: Ionic liquids as novel guests for cucurbit[6]uril in neutral water. Chem. Commun. 9, 1070–1072 (2008)

    Article  Google Scholar 

  36. Zhao, N., Liu, L., Biedermann, F., Scherman, O.A.: Binding studies on CB[6] with a series of 1-alkyl-3-methylimidazolium ionic liquids in an aqueous system. Chem. Asian J. 5, 530–537 (2010)

    Article  CAS  Google Scholar 

  37. Liu, L., Wang, J., Xu, X.L., Wang, B.C.: Supramolecular capsules of cucurbit[6]uril and controlled release. J. Inclusion Phenom. Macrocycl. Chem. 80, 437–441 (2014)

    Article  CAS  Google Scholar 

  38. Watkins, C.B.: The use of 1-methylcyclopropene (1-MCP) on fruits and vegetables. Biotechnol. Adv. 24, 389–409 (2006)

    Article  CAS  Google Scholar 

  39. Zhang, Q., Zhen, Z., Jiang, H., Li, X.G., Liu, J.A.: Encapsulation of the ethylene inhibitor 1-methylcyclopropene by cucurbit[6]uril. J. Agric. Food Chem. 59, 10539–10545 (2011)

    Article  CAS  Google Scholar 

  40. Florea, M., Nau, W.M.: Strong binding of hydrocarbons to cucurbituril probed by fluorescent dye displacement: a supramolecular gas-sensing ensemble. Angew. Chem. Int. Ed. 50, 9338–9342 (2011)

    Article  CAS  Google Scholar 

  41. Yang, H., Tan, Y.B., Wang, Y.X.: Fabrication and properties of cucurbit[6]uril induced thermo-responsive supramolecular hydrogels. Soft Matter 5, 3511–3516 (2009)

    Article  CAS  Google Scholar 

  42. Shaikh, M., Mohanty, J., Bhasikuttan, A.C., Uzunova, V.D., Nau, W.M., Pal, H.: Salt-induced guest relocation from a macrocyclic cavity into a biomolecular pocket: interplay between cucurbit[7]uril and albumin. Chem. Commun. 31, 3681–3683 (2008)

    Article  Google Scholar 

  43. Pischel, U., Uzunova, V.D., Remon, P., Nau, W.M.: Supramolecular logic with macrocyclic input and competitive reset. Chem. Commun. 46, 2635–2637 (2010)

    Article  CAS  Google Scholar 

  44. Carvalho, C.P., Uzunova, V.D., Da Silva, J.P., Nau, W.M., Pischel, U.: A photoinduced pH jump applied to drug release from cucurbit[7]uril. Chem. Commun. 47, 8793–8795 (2011)

    Article  CAS  Google Scholar 

  45. Ban, T., Hamada, D., Hasegawa, K., Naiki, H., Goto, Y.: Direct observation of amyloid fibril growth monitored by thioflavin T fluorescence. J. Biol. Chem. 278, 16462–16465 (2003)

    Article  CAS  Google Scholar 

  46. Choudhury, S.D., Mohanty, J., Pal, H., Bhasikuttan, A.C.: Cooperative metal ion binding to a cucurbit[7]uril-thioflavin T complex: demonstration of a stimulus-responsive fluorescent supramolecular capsule. J. Am. Chem. Soc. 132, 1395–1401 (2010)

    Article  CAS  Google Scholar 

  47. Nau, W.M.: Supramolecular capsules: under control. Nat. Chem. 2, 248–250 (2010)

    Article  CAS  Google Scholar 

  48. Balia Singh, R., Mahanta, S., Guchhait, N.: Study of interaction of proton transfer probe 1-hydroxy-2-naphthaldehyde with serum albumins: a spectroscopic study. J. Photochem. Photobiol. B 91, 1–8 (2008)

    Article  CAS  Google Scholar 

  49. Mandal, S., Rao, V.G., Ghatak, C., Pramanik, R., Sarkar, S., Sarkar, N.: Photophysics and photodynamics of 1′-hydroxy-2′-acetonaphthone (HAN) in micelles and nonionic surfactants forming vesicles: a comparative study of different microenvironments of surfactant assemblies. J. Phys. Chem. B 115, 12108–12119 (2011)

    Article  CAS  Google Scholar 

  50. Banik, D., Kuchlyan, J., Roy, A., Kundu, N., Sarkar, N.: Stimuli-sensitive breathing of Cucurbit[7]uril cavity: monitoring through the environment responsive fluorescence of 1′-hydroxy-2′-acetonaphthone (HAN). J. Phys. Chem. B 119, 2310–2322 (2015)

    Article  CAS  Google Scholar 

  51. Oun, R., Plumb, J.A., Wheate, N.J.: A cisplatin slow-release hydrogel drug delivery system based on a formulation of the macrocycle cucurbit[7]uril, gelatin and polyvinyl alcohol. J. Inorg. Biochem. 134, 100–105 (2014)

    Article  CAS  Google Scholar 

  52. Silva, G.L., Ediz, V., Yaron, D., Armitage, B.A.: Experimental and computational investigation of unsymmetrical cyanine dyes: understanding torsionally responsive fluorogenic dyes. J. Am. Chem. Soc. 129, 5710–5718 (2007)

    Article  CAS  Google Scholar 

  53. Mohanty, J., Thakur, N., Choudhury, S.D., Barooah, N., Pal, H., Bhasikuttan, A.C.: Recognition-mediated light-up of thiazole orange with cucurbit[8]uril: exchange and release by chemical stimuli. J. Phys. Chem. B 116, 130–135 (2012)

    Article  CAS  Google Scholar 

  54. Appel, E.A., Loh, X.J., Jones, S.T., Biedermann, F., Dreiss, C.A., Scherman, O.A.: Ultrahigh-water-content supramolecular hydrogels exhibiting multistimuli responsiveness. J. Am. Chem. Soc. 134, 11767–11773 (2012)

    Article  CAS  Google Scholar 

  55. Xu, X., Appel, E.A., Liu, X., Parker, R.M., Scherman, O.A., Abell, C.: Formation of cucurbit[8]uril-based supramolecular hydrogel beads using droplet-based microfluidics. Biomacromolecules. 16, 2743–2749 (2015)

    Article  CAS  Google Scholar 

  56. Appel, E.A., Loh, X.J., Jones, S.T., Dreiss, C.A., Scherman, O.A.: Sustained release of proteins from high water content supramolecular polymer hydrogels. Biomaterials 33, 4646–4652 (2012)

    Article  CAS  Google Scholar 

  57. Tian, F., Jiao, D., Biedermann, F., Scherman, O.A.: Orthogonal switching of a single supramolecular complex. Nat. Commun. 3, 1207 (2012)

    Article  Google Scholar 

  58. del Barrio, J., Horton, P.N., Lairez, D., Lloyd, G.O., Toprakcioglu, C., Scherman, O.A.: Photocontrol over cucurbit[8]uril complexes: stoichiometry and supramolecular polymers. J. Am. Chem. Soc. 135, 11760–11763 (2013)

    Article  Google Scholar 

  59. Lan, Y., Wu, Y.C., Karas, A., Scherman, O.A.: Photoresponsive hybrid raspberry-like colloids based on cucurbit[8]uril host–guest interactions. Angew. Chem. Int. Ed. 53, 2166–2169 (2014)

    Article  CAS  Google Scholar 

  60. Stoffelen, C., Voskuhl, J., Jonkheijm, P., Huskens, J.: Dual stimuli-responsive self-assembled supramolecular nanoparticles. Angew. Chem. Int. Ed. 53, 3400–3404 (2014)

    Article  CAS  Google Scholar 

  61. Jeon, W.S., Kim, H.J., Lee, C., Kim, K.: Control of the stoichiometry in host–guest complexation by redox chemistry of guests: inclusion of methylviologen in cucurbit[8]uril. Chem. Commun. 17, 1828–1829 (2002)

    Article  Google Scholar 

  62. Moon, K., Grindstaff, J., Sobransingh, D., Kaifer, A.E.: Cucurbit[8]uril-mediated redox-controlled self-assembly of viologen-containing dendrimers. Angew. Chem. Int. Ed. 43, 5496–5499 (2004)

    Article  CAS  Google Scholar 

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Acknowledgements

The project was supported by the National Natural Science Foundation of China (No. 21003123), and the Fundamental Research Funds for the Central Universities. We thank the reviewers for their helpful comments and suggestions.

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  1. Dalian University of Technology, Dalian, 116024, China

    Li Liu

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Liu, L. Controlled release from cucurbituril. J Incl Phenom Macrocycl Chem 87, 1–12 (2017). https://doi.org/10.1007/s10847-016-0683-3

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