Supramolecular chemistry involves non-covalent interactions and specific molecular recognition of molecules/analytes by host molecules or supramolecules. These events are present in synthesis, catalysis, chiral separations, design of sensors, cell signaling processes and drug transport by carriers. The typical behavior of supramolecules is derived from their ability to build well-structured self-assembled and self-organized entities. Cavitands are a particular group of supramolecules possessing a cavity capable to include a variety of compounds thanks to host-guest non-covalent interactions developed among cavitands and analytes. Some typical cavitands are crown ethers, calixarenes, cucurbiturils, porphyrins and cyclodextrins. The two latter families are natural product cavitands that are generally considered models for molecular recognition of cations and organic and inorganic guest molecules, being attractive host molecules from the sustainability point of view. The natural cyclodextrins (α, β and γ-cd) are obtained with reasonable cost by enzymatic treatment of starch under adequate temperature conditions. They are profusely used in pharmaceutical, food and cosmetic industries due to their very low toxicity and side effects. This review is focused on the relevance andapplications of cyclodextrins in pharmaceuticaltechnology for their ability to increase solubility and stabilize drug molecules, thereby enhancing their bioavailability. The association of cyclodextrins with diverse nanostructured materials, i.e., carbon nanotubes, magnetic nanoparticles, silica and molecularly imprinted polymers, allows to synergize the properties of cyclodextrins and these nanostructured materials to reach highly specific molecular recognition of analytes. The exploitation of these benefits for analytical sample pre-treatment and chiral chromatographic separations are described. The use of cyclodextrins as mobile phases additives in hplc provides interesting results for green and sustainable chromatographic separations. Polymers incorporating cyclodextrins show exceptional adsorption properties for retaining toxic compounds and persistent organic pollutants from soils and water samples, allowing satisfactory recoveries of these environmental samples according to the stockholm convection principles.

1. Shenderovich IG. Editorial to the Special Issue “Gulliver in the Country of Lilliput: An Interplay of Noncovalent Interactions.” Molecules. 2020; 26(1): 158. doi: 10.3390/molecules26010158
2. Ariga K, Kunitake T. Supramolecular Chemistry—Fundamentals and Applications. Springer Berlin Heidelberg; 2006. doi: 10.1007/b137036
3. Schneider H. Binding Mechanisms in Supramolecular Complexes. Angewandte Chemie International Edition. 2009; 48(22): 3924-3977. doi: 10.1002/anie.200802947
4. Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present and future. Nature Reviews Drug Discovery. 2004; 3(12): 1023-1035. doi: 10.1038/nrd1576
5. Lagona J, Mukhopadhyay P, Chakrabarti S, et al. The Cucurbit[n]uril Family. Angewandte Chemie International Edition. 2005; 44(31): 4844-4870. doi: 10.1002/anie.200460675
6. Gavvala K, Sengupta A, Hazra P. Modulation of Photophysics and pKa Shift of the Anti‐cancer Drug Camptothecin in the Nanocavities of Supramolecular Hosts. ChemPhysChem. 2013; 14(3): 532-542. doi: 10.1002/cphc.201200879
7. Li J. Cyclodextrin inclusion polymers forming hydrogels. Adv polym sci. 2009; 175-203. doi: 10.1007/12_2008_9
8. Kang SO, Llinares JM, Day VW, et al. Cryptand-like anion receptors. Chemical Society Reviews. 2010; 39(10): 3980. doi: 10.1039/c0cs00083c
9. Anderson J, Berthod A, Pino V, Stalcup AM. Analytical separation science. Wiley-Vch; 2016.
10. Szabó Z, Foroughbakhshfasaei M, Gál R, et al. Chiral separation of lenalidomide by liquid chromatography on polysaccharide‐type stationary phases and by capillary electrophoresis using cyclodextrin selectors. Journal of Separation Science. 2018; 41(6): 1414-1423. doi: 10.1002/jssc.201701211
11. Li Z, Zhou K, Lai Y, et al. Synthesis of Calix[4]proline Derivatives and Their Chiral Recognition for Enantiomers of Mandelic Acid (Chinese). Chinese Journal of Organic Chemistry. 2015; 35(7): 1531. doi: 10.6023/cjoc201502018
12. Crini G. Review: A History of Cyclodextrins. Chemical Reviews. 2014; 114(21): 10940-10975. doi: 10.1021/cr500081p
13. Dodziuk H. Cyclodextrins and Their Complexes. Wiley-Vch; 2006. doi: 10.1002/3527608982
14. Bilensoy E. Cyclodextrins in Pharmaceutics, Cosmetics, and Biomedicine. John Wiley & Sons; 2011. doi: 10.1002/9780470926819
15. Kurkov SV, Loftsson T. Cyclodextrins. International Journal of Pharmaceutics. 2013; 453(1): 167-180. doi: 10.1016/j.ijpharm.2012.06.055
16. Uekama K, Hirayama F. Improvement of Drug Properties by Cyclodextrins. The Practice of Medicinal Chemistry. Published online 2008: 813-840. doi: 10.1016/b978-0-12-374194-3.00040-8
17. Popielec A, Loftsson T. Effects of cyclodextrins on the chemical stability of drugs. International Journal of Pharmaceutics. 2017; 531(2): 532-542. doi: 10.1016/j.ijpharm.2017.06.009
18. Muñoz-Botella S, MartÍN MA, Del Castillo B, et al. Differentiating geometrical isomers of retinoids and controlling their photo-isomerization by complexation with cyclodextrins. Anal chim acta. 2002; 468: 161-170. doi: 10.1016/S0003-2670(02)00629-3
19. Saokham P, Muankaew C, Jansook P, et al. Solubility of Cyclodextrins and Drug/Cyclodextrin Complexes. Molecules. 2018; 23(5): 1161. doi: 10.3390/molecules23051161
20. González-Ruiz V, Olives AI, Martín MA. A down-scaled fluorimetric determination of the solubility properties of drugs to minimize waste generation. Green Chemistry. 2013; 15(9): 2558. doi: 10.1039/c3gc40974k
21. Buszewski B, Szultka M. Past, Present, and Future of Solid Phase Extraction: A Review. Critical Reviews in Analytical Chemistry. 2012; 42(3): 198-213. doi: 10.1080/07373937.2011.645413
22. Andrade-Eiroa A, Canle M, Leroy-Cancellieri V, et al. Solid-phase extraction of organic compounds: A critical review (Part I). TrAC Trends in Analytical Chemistry. 2016; 80: 641-654. doi: 10.1016/j.trac.2015.08.015
23. Andrade-Eiroa A, Canle M, Leroy-Cancellieri V, et al. Solid-phase extraction of organic compounds: A critical review. part ii. TrAC Trends in Analytical Chemistry. 2016; 80: 655-667. doi: 10.1016/j.trac.2015.08.014
24. Płotka-Wasylka J, Szczepańska N, de la Guardia M, et al. Modern trends in solid phase extraction: New sorbent media. TrAC Trends in Analytical Chemistry. 2016; 77: 23-43. doi: 10.1016/j.trac.2015.10.010
25. Mehdinia A, Aziz-Zanjani MO. Advances for sensitive, rapid and selective extraction in different configurations of solid-phase microextraction. TrAC Trends in Analytical Chemistry. 2013; 51: 13-22. doi: 10.1016/j.trac.2013.05.013
26. Trotta F, Zanetti M, Cavalli R. Cyclodextrin-based nanosponges as drug carriers. Beilstein Journal of Organic Chemistry. 2012; 8: 2091-2099. doi: 10.3762/bjoc.8.235
27. Swaminathan S, Pastero L, Serpe L, et al. Cyclodextrin-based nanosponges encapsulating camptothecin: Physicochemical characterization, stability and cytotoxicity. European Journal of Pharmaceutics and Biopharmaceutics. 2010; 74(2): 193-201. doi: 10.1016/j.ejpb.2009.11.003
28. Sherje AP, Dravyakar BR, Kadam D, et al. Cyclodextrin-based nanosponges: A critical review. Carbohydrate Polymers. 2017; 173: 37-49. doi: 10.1016/j.carbpol.2017.05.086
29. Cai K, Li J, Luo Z, et al. β-Cyclodextrin conjugated magnetic nanoparticles for diazepam removal from blood. Chemical Communications (Chinese). 2011; 47(27): 7719. doi: 10.1039/c1cc11855b
30. Gaber Ahmed GH, Badía Laíño R, García Calzón JA, et al. Magnetic nanoparticles grafted with β-cyclodextrin for solid-phase extraction of 5-hydroxy-3-indole acetic acid. Microchimica Acta. 2014; 181(9-10): 941-948. doi: 10.1007/s00604-014-1192-y
31. Azzouz A, Kailasa SK, Lee SS, et al. Review of nanomaterials as sorbents in solid-phase extraction for environmental samples. TrAC Trends in Analytical Chemistry. 2018; 108: 347-369. doi: 10.1016/j.trac.2018.08.009
32. Xu Z, Kuang D, Liu L, et al. Selective adsorption of norfloxacin in aqueous media by an imprinted polymer based on hydrophobic and electrostatic interactions. Journal of Pharmaceutical and Biomedical Analysis. 2007; 45(1): 54-61. doi: 10.1016/j.jpba.2007.05.024
33. Lay S, Ni X, Yu H, et al. State‐of‐the‐art applications of cyclodextrins as functional monomers in molecular imprinting techniques: a review. Journal of Separation Science. 2016; 39(12): 2321-2331. doi: 10.1002/jssc.201600003
34. Ikai T, Okamoto Y. Structure Control of Polysaccharide Derivatives for Efficient Separation of Enantiomers by Chromatography. Chemical Reviews. 2009; 109(11): 6077-6101. doi: 10.1021/cr8005558
35. Zhou J, Yang B, Tang J, et al. Cationic cyclodextrin clicked chiral stationary phase for versatile enantioseparations in high-performance liquid chromatography. Journal of Chromatography A. 2016; 1467: 169-177. doi: 10.1016/j.chroma.2016.06.030
36. Silva M, Pérez-Quintanilla D, Morante-Zarcero S, et al. Ordered mesoporous silica functionalized with β- cyclodextrin derivative for stereoisomer separation of flavanones and flavanone glycosides by nano-liquid chromatography and capillary electrochromatography. Journal of Chromatography A. 2017; 1490: 166-176. doi: 10.1016/j.chroma.2017.02.012
37. Yao X, Tan TTY, Wang Y. Thiol–ene click chemistry derived cationic cyclodextrin chiral stationary phase and its enhanced separation performance in liquid chromatography. Journal of Chromatography A. 2014; 1326: 80-88. doi: 10.1016/j.chroma.2013.12.054
38. Pang L, Zhou J, Tang J, et al. Evaluation of perphenylcarbamated cyclodextrin clicked chiral stationary phase for enantioseparations in reversed phase high performance liquid chromatography. Journal of Chromatography A. 2014; 1363: 119-127. doi: 10.1016/j.chroma.2014.08.040
39. Kučerová G, Procházková H, Kalíková K, et al. Sulfobutylether-β-cyclodextrin as a chiral selector for separation of amino acids and dipeptides in chromatography. Journal of Chromatography A. 2016; 1467: 356-362. doi: 10.1016/j.chroma.2016.07.061
40. Li L, Lurie IS. Regioisomeric and enantiomeric analyses of 24 designer cathinones and phenethylamines using ultra high performance liquid chromatography and capillary electrophoresis with added cyclodextrins. Forensic Science International. 2015; 254: 148-157. doi: 10.1016/j.forsciint.2015.06.026
41. Tong S, Zhang H, Shen M, et al. Enantioseparation of mandelic acid derivatives by high performance liquid chromatography with substituted β-cyclodextrin as chiral mobile phase additive and evaluation of inclusion complex formation. Journal of Chromatography B. 2014; 962: 44-51. doi: 10.1016/j.jchromb.2014.05.026
42. Olives AI, González-Ruiz V, Martín MA. Sustainable and Eco-Friendly Alternatives for Liquid Chromatographic Analysis. ACS Sustainable Chemistry & Engineering. 2017; 5(7): 5618-5634. doi: 10.1021/acssuschemeng.7b01012
43. Dembek M, Bocian S. Pure water as a mobile phase in liquid chromatography techniques. TrAC Trends in Analytical Chemistry. 2020; 123: 115793. doi: 10.1016/j.trac.2019.115793
44. González-Ruiz V, Olives AI, Martín MA. SPE/RP-HPLC using C1 columns: an environmentally friendly alternative to conventional reverse-phase separations for quantitation of beta-carboline alkaloids in human serum samples. Analytical and Bioanalytical Chemistry. 2010; 400(2): 395-401. doi: 10.1007/s00216-010-4562-2
45. León AG, Olives AI, del Castillo B, et al. Influence of the presence of methyl cyclodextrins in high-performance liquid chromatography mobile phases on the separation of β-carboline alkaloids. Journal of Chromatography A. 2008; 1192(2): 254-258. doi: 10.1016/j.chroma.2008.03.075
46. González-Ruiz V, León AG, Olives AI, et al. Eco-friendly liquid chromatographic separations based on the use of cyclodextrins as mobile phase additives. Green Chem. 2011; 13(1): 115-126. doi: 10.1039/c0gc00456a
47. Kawano S, Kida T, Miyawaki K, et al. Cyclodextrin Polymers as Highly Effective Adsorbents for Removal and Recovery of Polychlorobiphenyl (PCB) Contaminants in Insulating Oil. Environmental Science & Technology. 2014; 48(14): 8094-8100. doi: 10.1021/es501243v
48. Alsbaiee A, Smith BJ, Xiao L, et al. Rapid removal of organic micropollutants from water by a porous β- cyclodextrin polymer. Nature. 2015; 529(7585): 190-194. doi: 10.1038/nature16185
49. Bhattarai B, Muruganandham M, Suri RPS. Development of high efficiency silica coated β-cyclodextrin polymeric adsorbent for the removal of emerging contaminants of concern from water. Journal of Hazardous Materials. 2014; 273: 146-154. doi: 10.1016/j.jhazmat.2014.03.044
50. Zhou Y, Cheng G, Chen K, et al. Adsorptive removal of bisphenol A, chloroxylenol, and carbamazepine from water using a novel β-cyclodextrin polymer. Ecotoxicology and Environmental Safety. 2019; 170: 278-285. doi: 10.1016/j.ecoenv.2018.11.117
51. Tang P, Sun Q, Zhao L, et al. A simple and green method to construct cyclodextrin polymer for the effective and simultaneous estrogen pollutant and metal removal. Chemical Engineering Journal. 2019; 366: 598-607. doi: 10.1016/j.cej.2019.02.117
52. Carvalho LB de, Carvalho TG, Magriotis ZM, et al. Cyclodextrin/silica hybrid adsorbent for removal of methylene blue in aqueous media. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2012; 78(1-4): 77-87. doi: 10.1007/s10847-012-0272-z
53. Wang S, Li Y, Fan X, et al. β-cyclodextrin functionalized graphene oxide: an efficient and recyclable adsorbent for the removal of dye pollutants. Frontiers of Chemical Science and Engineering. 2015; 9(1): 77-83. doi: 10.1007/s11705-014-1450-x
54. Shao D, Sheng G, Chen C, et al. Removal of polychlorinated biphenyls from aqueous solutions using β- cyclodextrin grafted multiwalled carbon nanotubes. Chemosphere. 2010; 79(7): 679-685. doi: 10.1016/j.chemosphere.2010.03.008
55. Zhang F, Wu W, Sharma S, et al. Synthesis of Cyclodextrin-functionalized Cellulose Nanofibril Aerogel as a Highly Effective Adsorbent for Phenol Pollutant Removal. BioResources. 2015; 10(4). doi: 10.15376/biores.10.4.7555-7568
56. Qin X, Bai L, Tan Y, et al. β-Cyclodextrin-crosslinked polymeric adsorbent for simultaneous removal and stepwise recovery of organic dyes and heavy metal ions: Fabrication, performance and mechanisms. Chemical Engineering Journal. 2019; 372: 1007-1018. doi: 10.1016/j.cej.2019.05.006
57. Zhao F, Repo E, Yin D, et al. EDTA-Cross-Linked β-Cyclodextrin: An Environmentally Friendly Bifunctional Adsorbent for Simultaneous Adsorption of Metals and Cationic Dyes. Environmental Science & Technology. 2015; 49(17): 10570-10580. doi: 10.1021/acs.est.5b02227