Selective Removal of Purines from Aqueous Solution Using Cucurbit[N]Uril: A Comprehensive Review

Purine bases and their metabolites, including adenine, guanine, xanthine, hypoxanthine, uric acid, and methylxanthines such as caffeine, are essential biological compounds that have increasingly emerged as environmentally relevant micropollutants due to widespread human consumption and their incomplete removal by conventional wastewater treatment processes. Their high water solubility, structural similarity, and persistence at trace concentrations in complex aqueous matrices make selective removal particularly challenging. This review examines the sources, environmental significance, chemical behavior, and health implications of purines in aquatic systems, while critically assessing the limitations of existing treatment technologies such as conventional adsorption, membrane filtration, biological degradation, and advanced oxidation processes, which often suffer from poor selectivity, high energy demand, fouling, or incomplete mineralization. Emphasis is placed on cucurbit[n]urils (Q[n]) as a promising supramolecular platform for the selective removal of purines from water. The unique molecular architecture of Q[n], characterized by hydrophobic cavities and carbonyl-lined portals, enables highly specific host–guest interactions driven by size complementarity, hydrophobic inclusion, hydrogen bonding, and ion–dipole interactions. The review highlights the influence of cucurbituril ring size on purine selectivity, competitive binding behavior in multicomponent systems, and the advantages of nonporous adaptive crystals for selective uptake under realistic conditions. Current challenges related to scalability, material stability, and process integration are discussed, alongside future perspectives for the rational design of next-generation Q[n]-based adsorbents. Overall, this work underscores the potential of cucurbituril-based supramolecular systems as precision-engineered tools for sustainable purine management in environmental and biomedical applications.

Purines; Cucurbit[n]urils; Supramolecular adsorption; Selective removal; Aqueous solutions; Emerging contaminants; Water treatment; Host-guest chemistry

1. Albou, E. M., Nouayti, A., El Mansour, A., & Ait Boughrous, A. (2025). Impact of Emerging Contaminants on Aquatic Ecosystems: A Mini-Review. Research in Ecology. https://doi.org/10.30564/re.v7i3.9809 [Google Scholar] [Crossref]

2. Alešković, M., & Šekutor, M. (2023). Overcoming barriers with non-covalent interactions: supramolecular recognition of adamantyl cucurbit[n]uril assemblies for medical applications. In RSC Medicinal Chemistry (Vol. 15, Issue 2, pp. 433–471). Royal Society of Chemistry. https://doi.org/10.1039/d3md00596h [Google Scholar] [Crossref]

3. Almeida, C., Neves, M. C., & Freire, M. G. (2021). Towards the Use of Adsorption Methods for the Removal of Purines from Beer. Molecules, 26(21), 6460. [Google Scholar] [Crossref]

4. https://doi.org/10.3390/molecules26216460 [Google Scholar] [Crossref]

5. Anastopoulos, I., Pashalidis, I., Orfanos, A. G., Manariotis, I. D., Tatarchuk, T., Sellaoui, L., Bonilla-Petriciolet, A., Mittal, A., & Núñez-Delgado, A. (2020). Removal of caffeine, nicotine and amoxicillin from (waste)waters by various adsorbents. A review. Journal of Environmental Management, 261, 110236. https://doi.org/10.1016/j.jenvman.2020.110236 [Google Scholar] [Crossref]

6. Armstrong, L., Chang, S. L., Clements, N., Hirani, Z., Kimberly, L. B., Odoi-Adams, K., Suating, P., Taylor, H. F., Trauth, S. A., & Urbach, A. R. (2024). Molecular recognition of peptides and proteins by cucurbit[n]urils: systems and applications. Chemical Society Reviews, 53(23), 11519–11556. https://doi.org/10.1039/D4CS00569D [Google Scholar] [Crossref]

7. Bera, P. P., Stein, T., Head-Gordon, M., & Lee, T. J. (2017). Mechanisms of the Formation of Adenine, Guanine, and Their Analogues in UV-Irradiated Mixed NH3 :H2O Molecular Ices Containing Purine. Astrobiology, 17(8), 771–785. https://doi.org/10.1089/ast.2016.1614 [Google Scholar] [Crossref]

8. Buerge, I. J., Poiger, T., Müller, M. D., & Buser, H.-R. (2006). Combined Sewer Overflows to Surface Waters Detected by the Anthropogenic Marker Caffeine. Environmental Science & Technology, 40(13), 4096–4102. https://doi.org/10.1021/es052553l [Google Scholar] [Crossref]

9. Chernikova, E. Y., & Berdnikova, D. V. (2020). Cucurbiturils in nucleic acids research. In Chemical Communications (Vol. 56, Issue 98, pp. 15360–15376). Royal Society of Chemistry. https://doi.org/10.1039/d0cc06583h [Google Scholar] [Crossref]

10. Colaco, V., Ramchandra, S., Priyanka, S., Datta, D., Dhas, N., Thakur, G., Vikash, B., & Alizadeh, B. (2025). Multifunctional application of supramolecular cucurbiturils as encapsulating hosts in drug delivery : A review. Elsevier - International Journal of Pharmaceutics, 681(June). https://doi.org/10.1016/j.ijpharm.2025.125801 [Google Scholar] [Crossref]

11. Das, D., Assaf, K. I., & Nau, W. M. (2019). Applications of Cucurbiturils in Medicinal Chemistry and Chemical Biology. In Frontiers in Chemistry (Vol. 7). Frontiers Media S.A. https://doi.org/10.3389/fchem.2019.00619 [Google Scholar] [Crossref]

12. Du, J., Liu, Y., Li, L., Yin, Q., Yu, D., He, P., Wang, N., Yuan, R., Yin, Z., Tu, Y., & Li, Y. (2025). Natural Polyphenol Pentagalloyl Glucose as a Potent Xanthine Oxidase Inhibitor for Hyperuricemia Treatment. Journal of Agricultural and Food Chemistry, 73(35), 21889–21904. https://doi.org/10.1021/acs.jafc.5c04078 [Google Scholar] [Crossref]

13. Francesconi, O., Ienco, A., Papi, F., Dolce, M., Catastini, A., Nativi, C., & Roelens, S. (2022). A Sulfonated Tweezer-Shaped Receptor Selectively Recognizes Caffeine in Water. The Journal of Organic Chemistry, 87(5), 2662–2667. https://doi.org/10.1021/acs.joc.1c02620 [Google Scholar] [Crossref]

14. Hübner, U., Spahr, S., Lutze, H., Wieland, A., Rüting, S., Gernjak, W., & Wenk, J. (2024). Advanced oxidation processes for water and wastewater treatment – Guidance for systematic future research. Heliyon, 10(9), e30402. https://doi.org/10.1016/j.heliyon.2024.e30402 [Google Scholar] [Crossref]

15. Jones, E. L., Mlotkowski, A. J., Hebert, S. P., Schlegel, H. B., & Chow, C. S. (2022). Calculations of pKa Values for a Series of Naturally Occurring Modified Nucleobases. The Journal of Physical Chemistry A, 126(9), 1518–1529. https://doi.org/10.1021/acs.jpca.1c10905 [Google Scholar] [Crossref]

16. Kanth P, C., Trivedi, M. U., Patel, K., Misra, N. M., & Pandey, M. K. (2021). Cucurbituril-Functionalized Nanocomposite as a Promising Industrial Adsorbent for Rapid Cationic Dye Removal. ACS Omega, 6(4), 3024–3036. https://doi.org/10.1021/acsomega.0c05400 [Google Scholar] [Crossref]

17. Khademi, Z., & Nikoofar, K. (2025). Applications of catalytic systems containing DNA nucleobases (adenine, cytosine, guanine, and thymine) in organic reactions. RSC Advances, 15(5), 3192–3218. https://doi.org/10.1039/D4RA07996E [Google Scholar] [Crossref]

18. Klarić, D., Borko, V., Parlov Vuković, J., Pilepić, V., Budimir, A., & Galić, N. (2025). Host–Guest Interactions of Cucurbit[7]uril with Nabumetone and Naproxen: Spectroscopic, Calorimetric, and DFT Studies in Aqueous Solution. Molecules, 30(12), 2558. https://doi.org/10.3390/molecules30122558 [Google Scholar] [Crossref]

19. Konstantin, A., Donald, M., James, C., Christopher, I., John, A., Bardelang, D., Udachin, K. A., Leek, D. M., Margeson, J. C., Chan, G., Ratcli, C. I., & Ripmeester, J. A. (2011). Cucurbit [ n ] urils ( n = 5 – 8 ): a comprehensive solid state study. Pubs.Acs.Org/Crystal, 11, 5598–5614. https://doi.org/doi.org/10.1021/cg201173j [Google Scholar] [Crossref]

20. Lambert, H., Castillo Bonillo, A., Zhu, Q., Zhang, Y.-W., & Lee, T.-C. (2022). Supramolecular gating of guest release from cucurbit[7]uril using de novo design. Npj Computational Materials, 8(1), 21. https://doi.org/10.1038/s41524-022-00702-0 [Google Scholar] [Crossref]

21. Li, M., Wen, F., Jiang, Y. N., Sun, N., Xing, S., & Wang, B. (2025). Emerging trends in cucurbit[n]uril-based sensing. In Coordination Chemistry Reviews (Vol. 542). Elsevier B.V. https://doi.org/10.1016/j.ccr.2025.216870 [Google Scholar] [Crossref]

22. Li, Q., Jie, K., & Huang, F. (2020a). Highly Selective Separation of Minimum‐Boiling Azeotrope Toluene/Pyridine by Nonporous Adaptive Crystals of Cucurbit[6]uril. Angewandte Chemie International Edition, 59(13), 5355–5358. https://doi.org/10.1002/anie.201916041 [Google Scholar] [Crossref]

23. Li, Q., Jie, K., & Huang, F. (2020b). Highly Selective Separation of Minimum‐Boiling Azeotrope Toluene/Pyridine by Nonporous Adaptive Crystals of Cucurbit[6]uril. Angewandte Chemie International Edition, 59(13), 5355–5358. https://doi.org/10.1002/anie.201916041 [Google Scholar] [Crossref]

24. Li, S., Wen, J., He, B., Wang, J., Hu, X., & Liu, J. (2020). Occurrence of caffeine in the freshwater environment: Implications for ecopharmacovigilance. Environmental Pollution, 263, 114371. https://doi.org/10.1016/j.envpol.2020.114371 [Google Scholar] [Crossref]

25. Li, Y.-Y., Li, J., Li, Y., Long, H.-P., Lin, W., Wang, Y.-K., Tang, R., Liu, X.-W., Jiang, D., Liu, S., Cao, D., Tan, G.-S., Xu, K.-P., & Wang, W.-X. (2024). Binding uric acid: a pure chemical solution for the treatment of hyperuricemia. RSC Advances, 14(33), 24165–24174. https://doi.org/10.1039/D4RA04626A [Google Scholar] [Crossref]

26. Mahajan, S., Lee, T.-C., Biedermann, F., Hugall, J. T., Baumberg, J. J., & Scherman, O. A. (2010). Raman and SERS spectroscopy of cucurbit[n]urils. Physical Chemistry Chemical Physics, 12(35), 10429. https://doi.org/10.1039/c0cp00071j [Google Scholar] [Crossref]

27. Mock, M. B., & Summers, R. M. (2024). Microbial metabolism of caffeine and potential applications in bioremediation. Journal of Applied Microbiology, 135(4). https://doi.org/10.1093/jambio/lxae080 [Google Scholar] [Crossref]

28. Muheyati, M., Wu, G., Li, Y., Pan, Z., & Chen, Y. (2024). Supramolecular nanotherapeutics based on cucurbiturils. In Journal of Nanobiotechnology (Vol. 22, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s12951-024-03024-z [Google Scholar] [Crossref]

29. Niu, J., Yu, J., Wu, X., Zhang, Y.-M., Chen, Y., Yu, Z., & Liu, Y. (2024). Host–guest binding between cucurbit[8]uril and amphiphilic peptides achieved tunable supramolecular aggregates for cancer diagnosis. Chemical Science, 15(34), 13779–13787. https://doi.org/10.1039/D4SC04261A [Google Scholar] [Crossref]

30. Osifová, Z., Šála, M., & Dračínský, M. (2023). Hydrogen-Bonding Interactions of 8-Substituted Purine Derivatives. ACS Omega, 8(28), 25538–25548. https://doi.org/10.1021/acsomega.3c03244 [Google Scholar] [Crossref]

31. Qadeer, A., Liu, M., Mohapatra, S., & Lai, R. W. S. (2025). Editorial: Legacy & emerging contaminants in the aquatic environment-bridging knowledge, policy, and future. Frontiers in Toxicology, 7. https://doi.org/10.3389/ftox.2025.1611852 [Google Scholar] [Crossref]

32. Qu, S., Li, Z., & Jia, Q. (2019). Detection of Purine Metabolite Uric Acid with Picolinic-Acid-Functionalized Metal–Organic Frameworks. ACS Applied Materials & Interfaces, 11(37), 34196–34202. https://doi.org/10.1021/acsami.9b07442 [Google Scholar] [Crossref]

33. Quintero-Jaramillo, J. A., Carrero-Mantilla, J. I., & Sanabria-González, N. R. (2021). A Review of Caffeine Adsorption Studies onto Various Types of Adsorbents. The Scientific World Journal, 2021, 1–18. https://doi.org/10.1155/2021/9998924 [Google Scholar] [Crossref]

34. Raczyńska, E. D., Gal, J.-F., Maria, P.-C., Kamińska, B., Igielska, M., Kurpiewski, J., & Juras, W. (2020). Purine tautomeric preferences and bond-length alternation in relation with protonation-deprotonation and alkali metal cationization. Journal of Molecular Modeling, 26(5), 93. https://doi.org/10.1007/s00894-020-4343-6 [Google Scholar] [Crossref]

35. Raj, R., Tripathi, A., Das, S., & Ghangrekar, M. M. (2021). Removal of caffeine from wastewater using electrochemical advanced oxidation process: A mini review. Case Studies in Chemical and Environmental Engineering, 4, 100129. https://doi.org/10.1016/j.cscee.2021.100129 [Google Scholar] [Crossref]

36. Regmi, C., Kshetri, Y. K., & Wickramasinghe, S. R. (2025). Hybrid combination of advanced oxidation process with membrane technology for wastewater treatment: gains and problems. Nanotechnology, 36(13), 132002. https://doi.org/10.1088/1361-6528/adb040 [Google Scholar] [Crossref]

37. Rigueto, C. V. T., Nazari, M. T., De Souza, C. F., Cadore, J. S., Brião, V. B., & Piccin, J. S. (2020). Alternative techniques for caffeine removal from wastewater: An overview of opportunities and challenges. Journal of Water Process Engineering, 35, 101231. [Google Scholar] [Crossref]

38. https://doi.org/10.1016/j.jwpe.2020.101231 [Google Scholar] [Crossref]

39. Shehata, N., Abo El-Ela, F. I., Singh, S., Ramamurthy, P. C., Khan, N. A., Mahmoud, R., Singh, J., & Rtimi, S. (2025). Management of caffeine in wastewater using nanolayered material: An integrated study of process kinetics, modeling, and toxicity assessment. Journal of Environmental Management, 393, 127011. https://doi.org/10.1016/j.jenvman.2025.127011 [Google Scholar] [Crossref]

40. Shen, Y., Qu, H., & Wu, G. (2023). Molecular insights into cucurbit[8]uril-mediated complexes: Enhanced interaction cooperation towards pseudostatic dynamics. Journal of Molecular Liquids, 391, 123266. https://doi.org/10.1016/j.molliq.2023.123266 [Google Scholar] [Crossref]

41. Shi, L., Wang, L., Li, M., & Liu, M. (2024). A cucurbit[8]uril based supramolecular assembly and its potential applications for the removal of dye and antibiotic from an aqueous medium. RSC Advances, 14(12), 8161–8166. https://doi.org/10.1039/d4ra00347k [Google Scholar] [Crossref]

42. Skorupa, A., Worwąg, M., & Kowalczyk, M. (2025). Analysis of the effect of caffeine on the efficiency of wastewater treatment processes by integrated methods. Desalination and Water Treatment, 322, 101198. https://doi.org/10.1016/j.dwt.2025.101198 [Google Scholar] [Crossref]

43. Sun, Z., He, Q., Gong, Z., Kalhor, P., Huai, Z., & Liu, Z. (2023). A General Picture of Cucurbit[8]uril Host–Guest Binding: Recalibrating Bonded Interactions. Molecules, 28(7), 3124. https://doi.org/10.3390/molecules28073124 [Google Scholar] [Crossref]

44. Vieira, L. R., Soares, A. M. V. M., & Freitas, R. (2022). Caffeine as a contaminant of concern: A review on concentrations and impacts in marine coastal systems. Chemosphere, 286, 131675. https://doi.org/10.1016/j.chemosphere.2021.131675 [Google Scholar] [Crossref]

45. Wang, W., Wang, Z., Li, K., Liu, Y., Xie, D., Shan, S., He, L., & Mei, Y. (2023). Adsorption of uremic toxins using biochar for dialysate regeneration. Biomass Conversion and Biorefinery, 13(13), 11499–11511. https://doi.org/10.1007/s13399-021-01946-4 [Google Scholar] [Crossref]

46. Wang, Z., Sun, C., Yang, K., Chen, X., & Wang, R. (2022). Cucurbituril‐Based Supramolecular Polymers for Biomedical Applications. Angewandte Chemie, 134(38). [Google Scholar] [Crossref]

47. https://doi.org/10.1002/ange.202206763 [Google Scholar] [Crossref]

48. Wong, A., Santos, A. M., Feitosa, M. H. A., Fatibello-Filho, O., Moraes, F. C., & Sotomayor, M. D. P. T. (2023). Simultaneous Determination of Uric Acid and Caffeine by Flow Injection Using Multiple-Pulse Amperometry. Biosensors, 13(7), 690. https://doi.org/10.3390/bios13070690 [Google Scholar] [Crossref]

49. Wu, J., & Yang, Y. (2021). Synthetic Macrocycle‐Based Nonporous Adaptive Crystals for Molecular Separation. Angewandte Chemie International Edition, 60(4), 1690–1701. https://doi.org/10.1002/anie.202006999 [Google Scholar] [Crossref]

50. Wu, Y., Sun, L., Chen, X., Liu, J., Ouyang, J., Zhang, X., Guo, Y., Chen, Y., Yuan, W., Wang, D., He, T., Zeng, F., Chen, H., Wu, S., & Zhao, Y. (2023). Cucurbit[8]uril-based water-dispersible assemblies with enhanced optoacoustic performance for multispectral optoacoustic imaging. Nature Communications, 14(1), 3918. https://doi.org/10.1038/s41467-023-39610-2 [Google Scholar] [Crossref]

51. Yang, Y., Wan, Y., Chen, H., Li, Y., Muñoz-Carpena, R., Zheng, Y., Huang, J., Zhang, Y., & Gao, B. (2025). Caffeine removal in wastewater: a comprehensive review of current treatment plants and small-scale innovations. Environmental Technology Reviews, 14(1), 594–612. https://doi.org/10.1080/21622515.2025.2512483 [Google Scholar] [Crossref]

52. Yin, H., Cheng, Q., Bardelang, D., & Wang, R. (2023). Challenges and Opportunities of Functionalized Cucurbiturils for Biomedical Applications. American Chemical Society, 3(9). https://doi.org/10.1021/jacsau.3c00273 [Google Scholar] [Crossref]

53. Zhang, C., Yuan, R., Chen, H., Zhou, B., Cui, Z., & Zhu, B. (2024). Advancements in Inorganic Membrane Filtration Coupled with Advanced Oxidation Processes for Wastewater Treatment. Molecules, 29(17), 4267. https://doi.org/10.3390/molecules29174267 [Google Scholar] [Crossref]

54. Zhang, Y., Zhang, G., Xiao, X., Li, Q., & Tao, Z. (2024). Cucurbit[n]uril-Based supramolecular separation materials. Coordination Chemistry Reviews, 514, 215889. [Google Scholar] [Crossref]

55. https://doi.org/https://doi.org/10.1016/j.ccr.2024.215889 [Google Scholar] [Crossref]

• Methane Emissions from Municipal Solid Waste - Case Study in Cai Rang District, Can Tho City, Vietnam
• Youth Activism, Intentional Integration of Policies to Raise Awareness on Climate Change Action among the Youth
• Breathing Spaces: Environmental & User Experience in Dhanmondi and Zigatola Multistoried Apartments, Dhaka, Bangladesh
• Effects of Solid Waste Disposal on Soil Quality in Makurdi Metropolis, Benue State, Nigeria
• Environmental Impact of Artisanal and Small-Scale Gold Mining in Borgu Local Government Area