Functional Supramolecular Aggregates From Cavitands Based on Resorcin[4]Arene: Assembly and Applications

Abstract

Supramolecular aggregates, formed through the highly directional and reversible noncovalent assembly of building blocks, represent a cornerstone of modern materials science, enabling the creation of complex architectures with emergent properties. Among the diverse molecular platforms available, resorcin[4]arene-derived cavitands have emerged as particularly powerful building units due to their intrinsic concave cavity, tunable geometry, and versatile functionalization capacity. This review highlights recent progress in the construction of functional supramolecular aggregates based on resorcin[4]arene cavitands, with a focus on their assembly strategies and wide-ranging applications. The review systematically covers several key types of aggregate systems: porous coordination aggregates (e.g., metal-organic frameworks [MOFs]) with stimuli-responsive properties, dynamic polymeric aggregates exhibiting self-healing behavior, sensing aggregates enabling differential detection, and therapeutic aggregates for combination therapy. These systems are unified by their exploitation of cavitands’ unique host-guest chemistry and their ability to form well-defined superstructures through various noncovalent interactions. We emphasize how the precise manipulation of cavitand structure directs the assembly process and dictates the functional output of the resulting aggregates. Finally, we outline current challenges and future opportunities in this field, highlighting the potential of cavitand-based aggregates to enable next-generation technologies in sensing, catalysis, biomedicine, and energy materials. This review is expected to provide valuable insights and inspiration for researchers working in supramolecular chemistry and aggregate science.

The construction of supramolecular aggregates triggered by macrocycles has become a thriving area of supramolecular chemistry. In this context, resorcinarene cavitands, a class of macrocyclic receptors with intrinsic cavities, have been drawn into the limelight because of their advantages, such as the concave-shaped structure, adjustable cavity size, favorable host-guest behavior, and ease of functionalization. They can induce organic and inorganic molecules to self-assemble into supramolecular aggregates through various bonding modes, including hydrophobic interactions, metal-ligand coordination, van der Waals forces, hydrogen bonding, electrostatic interactions, π-π stacking, and amphiphilic interactions. This minireview focuses on some representative resorcinarene cavitand-based assembly aggregates, including microporous MOFs, supramolecular polymers, sensor arrays, and multifunctional nanodrugs. Each section highlights recent advancements, structural characteristics, and functional applications of these aggregate systems. This review will provide useful information for researchers working on not only cavitand chemistry but also the chemistry of other macrocyclic hosts, and it will inspire new discoveries in the field of supramolecular assemblies and systems containing macrocyclic hosts.

Keywords

drug delivery / host-guest chemistry / resorcin[4]arene cavitands / self-assembly / sensing / supramolecular aggregates

References

[1] J. M. Lehn, “Supramolecular Chemistry: Where From? Where to?,” Chemical Society Reviews 46 (2017): 2378–2379.

[2] G. M. Whitesides, J. P. Mathias, and C. T. Seto, “Molecular Self-Assembly and Nanochemistry: A Chemical Strategy for the Synthesis of Nanostructures,” Science 254 (1991): 1312–1319.

[3] X. Yan, P. Zhu, and J. Li, “Self-assembly and Application of Diphenylalanine-based Nanostructures,” Chemical Society Reviews 39 (2010): 1877–1890.

[4] Q. D. Hu, G. P. Tang, and P. K. Chu, “Cyclodextrin-Based Host–Guest Supramolecular Nanoparticles for Delivery: From Design to Applications,” Accounts of Chemical Research 47 (2014): 2017–2025.

[5] T. Shimizu, M. Masuda, and H. Minamikawa, “Supramolecular Nanotube Architectures Based on Amphiphilic Molecules,” Chemical Reviews 105 (2005): 1401–1444.

[6] P. K. Vemula and G. John, “Crops: A Green Approach Toward Self-Assembled Soft Materials,” Accounts of Chemical Research 41 (2008): 769–782.

[7] X. Zhang and C. Wang, “Supramolecular Amphiphiles,” Chemical Society Reviews 40 (2011): 94–101.

[8] A. M. Yang, X. H. Qin, H. Y. Li, D. Yao, and F. P. Huang, “Subcomponent Self-assembly Approach in Molecular Cages and Its Implication on Solution Behavior,” Crystal Engineering Communications 27 (2025): 4634–4641.

[9] C. F. Liu, Y. F. Jin, J. Q. Li, Z. Y. Wang, J. X. Wang, and W. Tian, “Dynamic Covalent and Noncovalent Bonds Based Self-Assembled Biomaterials: From Construction to Biomedical Applications,” Chinese Journal of Chemistry 43 (2025): 2053–2068.

[10] M. C. Jimenez, C. D. Buchecker, and J. P. Sauvage, “Towards Synthetic Molecular Muscles: Contraction and Stretching of a Linear Rotaxane Dimer,” Angewandte Chemie International Edition 39 (2000): 3284–3287.

[11] V. Balzani, A. Credi, F. M. Raymo, and J. F. Stoddart, “Artificial Molecular Machines,” Angewandte Chemie International Edition 39 (2000): 3348–3391.

[12] E. Krieg, M. M. C. Bastings, P. Besenius, and B. Rybtchinski, “Supramolecular Polymers in Aqueous Media,” Chemical Reviews 116 (2016): 2414–2477.

[13] G. Yu, K. Jie, and F. Huang, “Supramolecular Amphiphiles Based on Host–Guest Molecular Recognition Motifs,” Chemical Reviews 115 (2015): 7240–7303.

[14] H. T. Feng, J. W. Y. Lam, and B. Z. Tang, “Self-assembly of AIEgens,” Coordination Chemistry Reviews 406 (2020): 213142.

[15] C. L. Deng, S. L. Murkli, and L. D. Isaacs, “Supramolecular Hosts as in Vivo Sequestration Agents for Pharmaceuticals and Toxins,” Chemical Society Reviews 49 (2020): 7516–7532.

[16] F. Huang and E. V. Anslyn, “Introduction: Supramolecular Chemistry,” Chemical Reviews 115 (2015): 6999–7000.

[17] K. I. Assaf and W. M. Nau, “Cucurbiturils: From Synthesis to High-affinity Binding and Catalysis,” Chemical Society Reviews 44 (2015): 394–418.

[18] M. C. Daniel and D. Astruc, “Gold Nanoparticles: Assembly, Supramolecular Chemistry, Quantum-Size-Related Properties, and Applications Toward Biology, Catalysis, and Nanotechnology,” Chemical Reviews 104 (2004): 293–346.

[19] T. Tozawa, J. T. Jones, and S. I. Swamy, “Porous Organic Cages,” Nature Materials 8 (2009): 973–978.

[20] P. Chakraborty, N. Roy, P. Biswas, et al., “Exploiting Urea-Carboxylate Synthon for Designing Supramolecular Topical Hydrogel via Simple Organic Salt Formation: Synthesis, Crystal Structures, and Anticancer Behavior Against Melanoma B16–F10 Cells,” Chemistry of Materials 36 (2024): 7317–7331.

[21] W. Zhang, M. Q. Liu, and Y. Luo, “Chiral Amplification and Regulation: Design and Applications of Circularly Polarized Luminescence-Active Materials Derived from Macrocyclic Compounds,” Aggregate 6 (2025): e70039.

[22] J. Zhang, T. Wu, C. Li, and J. Du, “A Glycopolymersome Strategy for ‘Drug-free’ treatment of Diabetic Nephropathy,” Journal of Controlled Release 372 (2024): 347–361.

[23] W. L. Jiang, B. Huang, X. L. Zhao, X. Shi, and H. B. Yang, “Strong Halide Anion Binding Within the Cavity of a Conformation-adaptive Phenazine-based Pd2L4 Cage,” Chem 9 (2023): 2655–2668.

[24] M. Fathalla, “Synthesis and Characterization of a Porphyrin-crown Ether Conjugate as a Potential Intermediate for Drug Delivery Application,” Journal of Porphyrins and Phthalocyanines 25 (2021): 95–101.

[25] S. J. Lockyer, G. F. S. Whitehead, G. A. Timco, E. J. L. McInnes, and R. E. P. Winpenny, “Hybrid Inorganic-Organic Rotaxanes and Related Compounds,” Chemistry – A European Journal 31 (2025): e202501067.

[26] I. Roy and J. F. Stoddart, “Cyclodextrin Metal–Organic Frameworks and Their Applications,” Accounts of Chemical Research 54 (2021): 1440–1453.

[27] X. C. Yin, P. Xu, and H. Y. Wang, “Applications of Crown Ether-based Materials for Enhancing Lithium Recovery From Brines,” Separation and Purification Technology 371 (2025): 133093.

[28] Z. Liu and Y. Liu, “Multicharged Cyclodextrin Supramolecular Assemblies,” Chemical Society Reviews 51 (2022): 4786–4827.

[29] T. Matsunaga, J. Kanazawa, T. Ichikawa, et al., “α-Cyclodextrin Encapsulation of Bicyclo[1.1.1]Pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane,” Angewandte Chemie International Edition 60 (2021): 2578–2582.

[30] H. Shigemitsu, K. Kawakami, Y. Nagata, et al., “Cyclodextrins With Multiple Pyrenyl Groups: An Approach to Organic Molecules Exhibiting Bright Excimer Circularly Polarized Luminescence,” Angewandte Chemie International Edition 61 (2022): e202114700.

[31] Z. X. Liu, X. Y. Dai, Y. H. Sun, and Y. Liu, “Organic Supramolecular Aggregates Based on Water-Soluble Cyclodextrins and Calixarenes,” Aggregate 1 (2020): 31–44.

[32] Y. C. Pan, X. Y. Hu, and D. S. Guo, “Biomedical Applications of Calixarenes: State of the Art and Perspectives,” Angewandte Chemie International Edition 60 (2021): 2768–2794.

[33] X. Y. Hu, R. Fu, and D. S. Guo, “Hypoxia-Responsive Host–Guest Drug Delivery System,” Accounts of Materials Research 4 (2023): 925–938.

[34] M. J. Gu, X. N. Han, W. C. Guo, Y. Han, and C. F. Chen, “Naphth[4]Arene: Synthesis, Conformations, and Application in Color-Tunable Supramolecular Crystalline Assemblies,” Angewandte Chemie International Edition 62 (2023): e202305214.

[35] R. Nag and C. P. Rao, “Calixarene-mediated Host–guest Interactions Leading to Supramolecular Assemblies: Visualization by Microscopy,” Chemical Communications 58 (2022): 6044–6063.

[36] K. Kanagaraj, J. Rebek, and Y. Yu, “Self-Assembled Hexameric Capsule: A Highly β-Selective O-glycosylation Reaction Enabled via Proton Wire Mechanism,” Green Synthesis & Catalysis 4 (2023): 7–9.

[37] Y. H. Liu, Y. M. Zhang, H. J. Yu, and Y. Liu, “Cucurbituril-Based Biomacromolecular Assemblies,” Angewandte Chemie International Edition 60 (2021): 3870–3880.

[38] Y. Zhang, G. Zhang, X. Xiao, Q. Li, and Z. Tao, “Cucurbit[n]Uril-Based Supramolecular Separation Materials,” Coordination Chemistry Reviews 514 (2024): 215889.

[39] H. Nie, Z. Wei, X. L. Ni, and Y. Liu, “Assembly and Applications of Macrocyclic-Confinement-Derived Supramolecular Organic Luminescent Emissions From Cucurbiturils,” Chemical Reviews 122 (2022): 9032–9077.

[40] P. H. Shan, J. H. Hu, M. Liu, Z. Tao, X. Xiao, and C. Redshaw, “Progress in Host–Guest Macrocycle/Pesticide Research: Recognition, Detection, Release and Application,” Coordination Chemistry Reviews 467 (2022): 214580.

[41] D. H. Tuo, T. H. Shi, S. Ohtani, and T. Ogoshi, “Responsive Pillar[n]Arene Materials,” Responsive Materials 2 (2024): e20230024.

[42] T. Zhao, W. Wu, and C. Yang, “Chiroptical Regulation of Macrocyclic Arenes With Flipping-induced Inversion of Planar Chirality,” Chemical Communications 59 (2023): 11469–11483.

[43] H. Zhu, Q. Li, W. Zhu, and F. Huang, “Pillararenes as Versatile Building Blocks for Fluorescent Materials,” Accounts of Materials Research 3 (2022): 658–668.

[44] X. Li, M. Shen, J. Yang, L. Liu, and Y. W. Yang, “Pillararene-Based Stimuli-Responsive Supramolecular Delivery Systems for Cancer Therapy,” Advanced Materials 36 (2024): 2313317.

[45] G. P. Sun, M. Z. Zuo, W. R. Qian, J. M. Jiao, X. Y. Hu, and L. Y. Wang, “Highly Efficient Artificial Light-Harvesting Systems Constructed in Aqueous Solution for Supramolecular Photocatalysis,” Green Synthesis & Catalysis 4 (2021): 32–37.

[46] X. Y. Chen, H. Chen, and J. F. Stoddart, “The Story of the Little Blue Box: A Tribute to Siegfried Hünig,” Angewandte Chemie International Edition 62 (2023): e202211387.

[47] X. Chi, J. Tian, D. Luo, H. Y. Gong, F. Huang, and J. L. Sessler, ““Texas-Sized” Molecular Boxes: From Chemistry to Applications,” Molecules 26 (2021): 2426.

[48] I. Neira, A. B. Gomezjose, M. Quintela, M. D. Garcia, and C. Peinador, “Dissecting the “Blue Box”: Self-Assembly Strategies for the Construction of Multipurpose Polycationic Cyclophanes,” Accounts of Chemical Research 53 (2020): 2336–2346.

[49] S. M. Biros and J. Rebek, “Structure and Binding Properties of Water-soluble Cavitands and Capsules,” Chemical Society Reviews 36 (2007): 93–104.

[50] Q. Zhang, L. Catti, and K. Tiefenbacher, “Catalysis inside the Hexameric Resorcinarene Capsule,” Accounts of Chemical Research 51 (2018): 2107–2114.

[51] H. R. Aziza, W. Yao, J. H. Jordan, and B. C. Gibb, “Dual Binding Modes of a Small Cavitand,” Supramolecular Chemistry 33 (2021): 266–271.

[52] K. Helttunena and P. Shahgaldian, “Self-assembly of Amphiphilic Calixarenes and Resorcinarenes in Water,” New Journal of Chemistry 34 (2010): 2704.

[53] P. A. Galea, P. Anzenbacher, and J. L. Sessler, “Calixpyrroles II,” Coordination Chemistry Reviews 222 (2001): 57–102.

[54] I. A. Rather, R. Ali, and A. Ali, “Recent Developments in calix[4]Pyrrole (C4P)-based Supramolecular Functional Systems,” Organic Chemistry Frontiers 9 (2022): 6416–6440.

[55] Z. Y. Zhang and C. Li, “Biphen[n]Arenes: Modular Synthesis, Customizable Cavity Sizes, and Diverse Skeletons,” Accounts of Chemical Research 55 (2022): 916–929.

[56] H. Chen, J. Fan, X. Hu, et al., “Biphen[n]Arenes,” Chemical Science 6 (2015): 197–202.

[57] C. F. Chen and Y. Han, “Triptycene-Derived Macrocyclic Arenes: From Calixarenes to Helicarenes,” Accounts of Chemical Research 51 (2018): 2093–2106.

[58] Z. Wang, N. Sikdar, S. Q. Wang, et al., “Soft Porous Crystal Based Upon Organic Cages That Exhibit Guest-Induced Breathing and Selective Gas Separation,” Journal of the American Chemical Society 141 (2019): 9408–9414.

[59] N. Sun, C. Wang, B. Yu, H. Wang, L. J. Barbour, and J. Jiang, “Stimuli-Responsive Porous Molecular Crystal With Reversible Modulation of Porosity,” ACS Applied Materials & Interfaces 14 (2022): 1519–1525.

[60] T. Hyodo, M. Tominaga, and K. Yamaguchi, “Guest-dependent Single-crystal-to-single-crystal Transformations in Porous Adamantane-bearing Macrocycles,” Crystal Engineering Communications 23 (2021): 1539–1543.

[61] M. Tominaga, S. Shinkawa, T. Hyodo, and K. Yamaguchi, “Dynamic Behavior of Macrocycle-based Organic Frameworks in Single-crystal to Single-crystal Guest Exchanges,” Crystal Engineering Communications 23 (2021): 7039–7043.

[62] D. Wang and Y. Zhao, “Rigid-Flexible Hybrid Porous Molecular Crystals With Guest-Induced Reversible Crystallinity,” Angewandte Chemie International Edition 62 (2023): e202217903.

[63] Y. Y. Liu, X. Y. Yu, Y. C. Pan, et al., “Supramolecular Systems for Bioapplications: Recent Research Progress in China,” Science China Chemistry 67 (2024): 1397–1441.

[64] Z. Liu, J. Chen, and C. Li, “Biphen[ n ]Arene-Based Supramolecular Materials,” Accounts of Materials Research 6 (2025): 765–778.

[65] F. Y. Chen, R. Fu, Z. Gong, C. Li, D. S. Guo, and K. Cai, “Ultrahigh-Affinity Molecular Recognition in Water and Biomedical Applications,” Angewandte Chemie International Edition (2025): e202500916.

[66] A. Pedrini, D. Marchetti, R. Pinalli, and C. Massera, “Stimuli-Responsive, Dynamic Supramolecular Organic Frameworks,” ChemPlusChem 88 (2023): e20230038.

[67] H. Zhao, Y. Li, C. Li, and D. S. Guo, “Macrocycle-containing Metal–organic Frameworks in Adsorption and Related Applications,” Journal of Materials Chemistry A 13 (2025): 23354–23376.

[68] Y. Yu, J. M. Yang, and J. Rebek, “Molecules in Confined Spaces: Reactivities and Possibilities in Cavitands,” Chem 6 (2020): 1265–1274.

[69] J. Rebek, “Molecular Behavior in Small Spaces,” Accounts of Chemical Research 42 (2009): 1660–1668.

[70] H. S. Ashbaugh, B. C. Gibb, and P. Suating, “Cavitand Complexes in Aqueous Solution: Collaborative Experimental and Computational Studies of the Wetting, Assembly, and Function of Nanoscopic Bowls in Water,” Journal of Physical Chemistry B 125 (2021): 3253–3268.

[71] K. Wang, Q. Liu, L. Zhou, H. Sun, X. Yao, and X. Y. Hu, “State-of-the-art and Recent Progress in Resorcinarene-based Cavitand,” Chinese Chemical Letters 34 (2023): 108559.

[72] L. Pirondini, A. G. Stendardo, S. Geremia, et al., “Dynamic Materials Through Metal-Directed and Solvent-Driven Self-Assembly of Cavitands,” Angewandte Chemie International Edition 42 (2003): 1384–1387.

[73] S. Mosca, Y. Yu, and J. Rebek, “Preparative Scale and Convenient Synthesis of a Water-soluble, Deep Cavitand,” Nature Protocols 11 (2016): 1371–1387.

[74] M. B. Hillyer, C. L. D. Gibb, P. Sokkalingam, J. H. Jordan, S. E. Ioup, and B. C. Gibb, “Synthesis of Water-Soluble Deep-Cavity Cavitands,” Organic Letters 18 (2016): 4048–4051.

[75] W. J. Ong, F. Bertani, E. Dalcanale, and T. M. Swager, “Redox Switchable Thianthrene Cavitands,” Synthesis 49 (2017): 358–364.

[76] Y. J. Zhu, M. K. Zhao, J. Rebek, and Y. Yu, “Recent Advances in the Applications of Water-soluble Resorcinarene-based Deep Cavitands,” ChemistryOpen 11 (2022): e20220002.

[77] M. Petroselli, Y. Q. Chen, J. Rebek, and Y. Yu, “Binding and Reactivity in Deep Cavitands Based on Resorcin[4]arene,” Green Synthesis & Catalysis 2 (2021): 123–130.

[78] F. Guagnini, A. Pedrini, T. M. Swager, C. Massera, and E. Dalcanale, “Solvent-responsive Cavitand Lanthanum Complex,” Dalton Transactions 48 (2019): 13732–13739.

[79] J. W. Barnett, M. R. Sullivan, J. A. Long, et al., “Spontaneous Drying of Non-polar Deep-cavity Cavitand Pockets in Aqueous Solution,” Nature Chemistry 12 (2020): 589–594.

[80] P. Jagadesan, S. R. Samanta, R. Choudhury, and V. Ramamurthy, “Container C Hemistry: M Anipulating Excited state Behavior of Organic Guests Within Cavitands That Form Capsules in Water,” Journal of Physical Organic Chemistry 30 (2017): e3728.

[81] Y. Zhu, M. Tang, H. Zhang, et al., “Water and the Cation−π Interaction,” Journal of the American Chemical Society 143 (2021): 12397–12403.

[82] T. Iwasawa, R. J. Hooley, and J. Rebek, “Stabilization of Labile Carbonyl Addition Intermediates by a Synthetic Receptor,” Science 317 (2007): 493–496.

[83] Y. S. Li, L. Escobar, Y. J. Zhu, et al., “Relative Hydrophilicities of Cis and Trans Formamides,” Proceedings National Academy of Sciences of USA 116 (2019): 19815–19820.

[84] N. Natarajan, E. Brenner, D. Semeril, D. Matt, and J. Harrowfield, “The Use of Resorcinarene Cavitands in Metal-Based Catalysis,” European Journal of Organic Chemistry 2017 (2017): 6100–6113.

[85] C. Gibson and J. Rebek, “Recognition and Catalysis in Allylic Alkylations,” Organic Letters 4 (2002): 1887–1890.

[86] H. E. Moll, D. Semeril, D. Matt, M. T. Youinou, and L. Toupet, “Synthesis of a Resorcinarene-based Tetraphosphine-cavitand and Its Use in Heck Reactions,” Organic & Biomolecular Chemistry 7 (2009): 495–501.

[87] M. Rao, W. H. Wu, and C. Yang, “Recent Progress on the Enantioselective Excited-State Photoreactions by Pre-Arrangement of Photosubstrate(s),” Green Synthesis and Catalysis 2 (2021): 131–144.

[88] R. Pinalli, A. Pedrini, and E. Dalcanale, “Environmental Gas Sensing With Cavitands,” Chemistry – A European Journal 24 (2018): 1010–1019.

[89] J. Chen, E. Z. Tabaie, B. L. Hickey, et al., “Selective Molecular Recognition and Indicator Displacement Sensing of Neurotransmitters in Cellular Environments,” ACS Sensors 8 (2023): 3195–3204.

[90] R. Pinalli, A. Pedrini, and E. Dalcanale, “Biochemical Sensing With Macrocyclic Receptors,” Chemical Society Reviews 47 (2018): 7006–7026.

[91] J. M. Yang, Y. Q. Chen, Y. Yu, P. Ballester, and J. Rebek, “Rigidified Cavitand Hosts in Water: Bent Guests, Shape Selectivity, and Encapsulation,” Journal of the American Chemical Society 143 (2021): 19517–19524.

[92] F. U. Rahman, J. M. Yang, Y. H. Wan, et al., “Binding Selectivity and Separation of p-functionalized Toluenes With a Metallo-cavitand in Water,” Chemical Communications 56 (2020): 6945–6948.

[93] Y. H. Wan, F. U. Rahman, J. Rebek, and Y. Yu, “Shape Selectivity of a Metallo Cavitand Host Allows Separation of n-Alkanes From Isooctane,” Chinese Journal of Chemistry 39 (2021): 1498–1502.

[94] C. L. D. Gibb, A. K. Sundaresan, V. Ramamurthy, and B. C. Gibb, “Templation of the Excited-State Chemistry of α-(n-Alkyl) Dibenzyl Ketones: How Guest Packing Within a Nanoscale Supramolecular Capsule Influences Photochemistry,” Journal of the American Chemical Society 130 (2008): 4069–4080.

[95] J. M. Yang, Y. Yu, and J. Rebek, “Selective Macrocycle Formation in Cavitands,” Journal of the American Chemical Society 143 (2021): 2190–2193.

[96] A. R. Renslo, F. C. Tucci, D. M. Rudkevich, and J. Rebek, “Synthesis and Assembly of Self-Complementary Cavitands,” Journal of the American Chemical Society 122 (2000): 4573–4582.

[97] K. Kobayashi and M. Yamanaka, “Self-assembled Capsules Based on Tetrafunctionalized Calix[4]Resorcinarene Cavitands,” Chemical Society Reviews 44 (2015): 449–466.

[98] F. Rahman, R. Wang, H. B. Zhang, et al., “Binding and Assembly of a Benzotriazole Cavitand in Water,” Angewandte Chemie International Edition 61 (2022): e202205534.

[99] G. V. Oshovsky, D. N. Reinhoudt, and W. Verboom, “Triple-Ion Interactions for the Construction of Supramolecular Capsules,” Journal of the American Chemical Society 128 (2006): 5270–5278.

[100] C. L. D. Gibb and B. C. Gibb, “Well-Defined, Organic Nanoenvironments in Water: the Hydrophobic Effect Drives a Capsular Assembly,” Journal of the American Chemical Society 126 (2004): 11408–11409.

[101] N. Nitta, M. Takatsuka, S. Kihara, R. Sekiya, and T. Haino, “Facile Synthesis of an Eight-Armed Star-Shaped Polymer via Coordination-Driven Self-Assembly of a Four-Armed Cavitand,” ACS Macro Letters 7 (2018): 1308–1311.

[102] P. Jacopozzi and E. Dalcanale, “Metal-Induced Self-Assembly of Cavitand-Based Cage Molecules,” Angewandte Chemie International Edition 36 (1997): 613–615.

[103] Q. Liu, M. Zuo, K. Wang, and X. Hu, “A Cavitand-based Supramolecular Artificial Light-harvesting System With Sequential Energy Transfer for Photocatalysis,” Chemical Communications 59 (2023): 13707–13710.

[104] G. S. Ananchenko, K. A. Udachin, A. Dubes, J. A. Ripmeester, T. Perrier, and A. W. Coleman, “Guest Exchange in Single Crystals of van der Waals Nanocapsules,” Angewandte Chemie International Edition 45 (2006): 1585–1588.

[105] E. Menozzi, R. Pinalli, E. A. Speets, B. J. Ravoo, E. Dalcanale, and D. N. Reinhoudt, “Surface-Confined Single Molecules: Assembly and Disassembly of Nanosize Coordination Cages on Gold (111),” Chemistry – A European Journal 10 (2004): 2199–2206.

[106] Y. Liu, T. Taira, M. C. Young, et al., “Protein Recognition by a Self-Assembled Deep Cavitand Monolayer on a Gold Substrate,” Langmuir 28 (2012): 1391–1398.

[107] P. Clement, S. Korom, C. Struzzi, et al., “Deep Cavitand Self-Assembled on Au NPs-MWCNT as Highly Sensitive Benzene Sensing Interface,” Advanced Functional Materials 25 (2015): 4011–4020.

[108] K. D. Schierbaum, T. Weiss, E. U. Thoden van Veizen, J. F. J. Engbersen, D. N. Reinhoudt, and W. Gopel, “Molecular Recognition by Self-Assembled Monolayers of Cavitand Receptors,” Science 265 (1994): 1413–1415.

[109] N. Nishimura and K. Kobayashi, “Self-Assembly of a Cavitand-Based Capsule by Dynamic Boronic Ester Formation,” Angewandte Chemie International Edition 47 (2008): 6255–6258.

[110] W. Pei, G. Xu, J. Yang, et al., “Versatile Assembly of Metal-Coordinated Calix[4]Resorcinarene Cavitands and Cages Through Ancillary Linker Tuning,” Journal of the American Chemical Society 139 (2017): 7648–7656.

[111] K. Su, W. Wang, S. Du, C. Ji, M. Zhou, and D. Yuan, “Reticular Chemistry in the Construction of Porous Organic Cages,” Journal of the American Chemical Society 142 (2020): 18060–18072.

[112] A. Galana and P. Ballester, “Stabilization of Reactive Species by Supramolecular Encapsulation,” Chemical Society Reviews 45 (2016): 1720–1737.

[113] S. Rojas and P. Horcajada, “Metal–Organic Frameworks for the Removal of Emerging Organic Contaminants in Water,” Chemical Reviews 120 (2020): 8378–8415.

[114] H. Furukawa, K. E. Cordova, M. Keeffe, and O. M. Yaghi, “The Chemistry and Applications of Metal-Organic Frameworks,” Science 341 (2013): 1230444.

[115] S. L. Griffin and N. R. Champness, “A Periodic Table of Metal-organic Frameworks,” Coordination Chemistry Reviews 414 (2020): 213295.

[116] R. Freund, O. Zaremba, G. Arnauts, et al., “The Current Status of MOF and COF Applications,” Angewandte Chemie, International Edition 60 (2021): 23975–24001.

[117] M. J. Zaworotko, “Engineering Porous Crystals to Do Different Things,” Nature Materials 23 (2024): 39–40.

[118] S. Kitagawa, “Porous Materials and the Age of Gas,” Angewandte Chemie International Edition 54 (2015): 10686–10687.

[119] S. B. Peh, A. Karmakar, and D. Zhao, “Multiscale Design of Flexible Metal–Organic Frameworks,” Trends Chem 2 (2020): 199–213.

[120] S. M. Morozova, A. Sharsheeva, M. I. Morozov, A. V. Vinogradov, and E. Heyawkins, “Bioresponsive Metal–organic Frameworks: Rational Design and Function,” Coordination Chemistry Reviews 431 (2021): 213682.

[121] Z. Li, B. Yao, C. Cheng, et al., “Versatile Structural Engineering of Metal–Organic Frameworks Enabling Switchable Catalytic Selectivity,” Advanced Materials 36 (2024): 2308427.

[122] Y. X. Ma, B. Gao, Y. Li, W. Wei, Y. Zhao, and J. F. Ma, “Macrocycle-Based Metal−Organic Frameworks with NO2‑Driven On/Off Switch of Conductivity,” ACS Applied Materials & Interfaces 13 (2021): 2706.

[123] M. Y. Yu, J. H. Liu, C. Liu, W. Y. Pei, and J. F. Ma, “Resorcin[4]Arene-based Microporous Metal–organic Framework/Reduced Graphene Oxide Composite as an Electrocatalyst for Effective and Simultaneous Determination of p-nitrophenol and o-nitrophenol Isomers,” Sensors and Actuators B-Chemistry 347 (2021): 130604.

[124] F. F. Wang, C. Liu, J. Yang, H. L. Xu, W. Y. Pei, and J. F. Ma, “A Sulfur-Containing Capsule-Based Metal-Organic Electrochemical Sensor for Super-Sensitive Capture and Detection of Multiple Heavy-Metal Ions,” Chemical Engineering Journal 438 (2022): 135639.

[125] X. H. Liang, A. X. Yu, X. J. Bo, D. Y. Du, and Z. M. Su, “Metal/Covalent-organic Frameworks-based Electrochemical Sensors for the Detection of Ascorbic Acid, Dopamine and Uric Acid,” Coordination Chemistry Reviews 497 (2023): 215427.

[126] Y. W. Liu, B. X. Wang, Q. Fu, et al., “Polyoxometalate-Based Metal–Organic Framework as Molecular Sieve for Highly Selective Semi-Hydrogenation of Acetylene on Isolated Single Pd Atom Sites,” Angewandte Chemie International Edition 60 (2021): 22522–22528.

[127] Y. H. Chen, H. Y. An, S. Z. Chang, et al., “Two Pseudo-polymorphic Porous POM-pillared MOFs for Sulfide-sulfoxide Transformation: Efficient Synergistic Effects of POM Precursors, Metal Sites and Microstructures,” Chinese Chemical Letters 34 (2023): 107856.

[128] J. H. Liu, Q. T. Shen, J. Yang, M. Y. Yu, and J. F. Ma, “Polyoxometalate-Templated Cobalt-Resorcin[4]Arene Frameworks: Tunable Structure and Lithium-Ion Battery Performance,” Inorganic Chemistry 60 (2021): 3729–3740.

[129] N. Roy, B. Bruchmann, and J. M. Lehn, “DYNAMERS: Dynamic Polymers as Self-healing Materials,” Chemical Society Reviews 44 (2015): 3786–3807.

[130] Y. Zhang and M. Barboiu, “Constitutional Dynamic Materials—Toward Natural Selection of Function,” Chemical Reviews 116 (2016): 809–834.

[131] W. Hu, V. Liberioux, J. Rossignol, et al., “Transient Supramolecular Polymers by pH-Gated Conformational Control of a Self-Assembling Cyclodextrin,” Angewandte Chemie International Edition (2025): e202507069.

[132] X. Ji, Z. Wang, W. Yuan, Z. Gao, and W. Tian, “Intrinsic Stimuli-responsive Main-chain Supramolecular Polymers Driven by Dative B ← N Bonds,” Chemical Communications 61 (2025): 5447–5450.

[133] C. Fouquey, J. M. Lehn, and A. M. Levelut, “Molecular Recognition Directed Self-Assembly of Supramolecular Liquid Crystalline Polymers From Complementary Chiral Components,” Advanced Materials 2 (1990): 254–257.

[134] V. Balzani, S. Campagna, G. Denti, A. Juris, S. Serroni, and M. Venturi, “Designing Dendrimers Based on Transition-Metal Complexes. Light-Harvesting Properties and Predetermined Redox Patterns,” Accounts of Chemical Research 31 (1998): 26–34.

[135] S. L. Li, T. Xiao, C. Lin, and L. Wang, “Advanced Supramolecular Polymers Constructed by Orthogonal Self-assembly,” Chemical Society Reviews 41 (2012): 5950–5968.

[136] R. M. Yebeutchou, F. Tancini, N. Demitri, S. Geremia, R. Mendichi, and E. Dalcanale, “Host–Guest Driven Self-Assembly of Linear and Star Supramolecular Polymers,” Angewandte Chemie International Edition 47 (2008): 4504–4508.

[137] F. Tancini, R. M. Yebeutchou, L. Pirondini, et al., “Host–Guest-Driven Copolymerization of Tetraphosphonate Cavitands,” Chemistry – A European Journal 16 (2010): 14313–14321.

[138] M. Dionisio, L. Ricci, G. Pecchini, et al., “Polymer Blending Through Host–Guest Interactions,” Macromolecules 47 (2014): 632–638.

[139] D. Masseroni, E. Rampazzo, F. Rastrelli, et al., “pH-responsive Host–guest Polymerization and Blending,” RSC Advances 5 (2015): 11334–11342.

[140] D. Zuccaccia, R. Pinalli, R. D. Zorzi, et al., “Hierarchical Self-assembly and Controlled Disassembly of a Cavitand-based Host–guest Supramolecular Polymer,” Polymer Chemistry 12 (2021): 389–401.

[141] R. Hoogenboom, D. Fournier, and U. S. Schubert, “Asymmetrical Supramolecular Interactions as Basis for Complex Responsive Macromolecular Architectures,” Chemical Communications (2008): 155–162.

[142] N. Nitta, M. Takatsuka, S. Kihara, T. Hirao, and T. Haino, “Self-Healing Supramolecular Materials Constructed by Copolymerization via Molecular Recognition of Cavitand-Based Coordination Capsules,” Angewandte Chemie International Edition 59 (2020): 16690–16697.

[143] A. T. Wright and E. V. Anslyn, “Differential Receptor Arrays and Assays for Solution-based Molecular Recognition,” Chemical Society Reviews 35 (2006): 14–28.

[144] S. B. Jo, J. H. Lee, J. Lee, M. M. Oh, and J. S. Lee, “Differential Sensing Approach as a Pattern-Based Discrimination for Biological Samples,” Chemistry – A European Journal 30 (2024): e202402871.

[145] J. H. Tian, Z. Zheng, Y. C. Pan, Y. Wang, and D. S. Guo, “Macrocycle-Based Differential Sensing: Design Strategies and Applications,” Responsive Materials 3 (2025): e20240036.

[146] W. Zhong and R. J. Hooley, “Combining Excellent Selectivity With Broad Target Scope: Biosensing With Arrayed Deep Cavitand Hosts,” Accounts of Chemical Research 55 (2022): 1035–1046.

[147] T. Minami, N. A. Esipenko, B. Zhang, L. Isaacs, and P. Anzenbacher, ““Turn-on” Fluorescent Sensor Array for Basic Amino Acids in Water,” Chemical Communications 50 (2014): 61–63.

[148] N. Bontempi, E. Biavardi, D. Bordiga, et al., “Probing Lysine Mono-methylation in Histone H3 Tail Peptides With an Abiotic Receptor Coupled to a Non-plasmonic Resonator,” Nanoscale 9 (2017): 8639–8646.

[149] A. Z. Haynes and M. Levine, “Detection of Anabolic Steroids via Cyclodextrin-promoted Fluorescence Modulation,” RSC Advances 10 (2020): 25108–25115.

[150] Z. Zheng, W. C. Geng, J. Gao, Y. J. Mu, and D. S. Guo, “Differential Calixarene Receptors Create Patterns That Discriminate Glycosaminoglycans,” Organic Chemistry Frontiers 5 (2018): 2685–2691.

[151] S. A. Minaker, K. D. Daze, M. C. F. Ma, and F. Hof, “Antibody-Free Reading of the Histone Code Using a Simple Chemical Sensor Array,” Journal of the American Chemical Society 134 (2012): 11674–11680.

[152] Y. Liu, L. Perez, A. D. Gill, et al., “Site-Selective Sensing of Histone Methylation Enzyme Activity via an Arrayed Supramolecular Tandem Assay,” Journal of the American Chemical Society 139 (2017): 10964–10967.

[153] R. J. Hooley and J. Rebek, “Chemistry and Catalysis in Functional Cavitands,” Chemistry & Biology 16 (2009): 255–264.

[154] M. M. Tang, K. Kanagaraj, J. Rebek, and Y. Yu, “Role of Rim Functions in Recognition and Selectivity of Small-Molecule Guests in Water-Soluble Cavitand Hosts,” Chemistry - An Asian Journal 17 (2022): e202200466.

[155] Y. Liu, L. Perez, M. Mettry, C. J. Easley, R. J. Hooley, and W. Zhong, “Self-Aggregating Deep Cavitand Acts as a Fluorescence Displacement Sensor for Lysine Methylation,” Journal of the American Chemical Society 138 (2016): 10746–10749.

[156] Y. Liu, L. Perez, M. Mettry, et al., “Site Selective Reading of Epigenetic Markers by a Dual-mode Synthetic Receptor Array,” Chemical Science 8 (2017): 3960–3970.

[157] J. Chen, P. Fasihianifard, A. A. P. Raz, et al., “Selective Recognition and Discrimination of Single Isomeric Changes in Peptide Strands With a Host : Guest Sensing Array,” Chemical Science 15 (2024): 1885–1893.

[158] J. Chen, P. Fasihianifard, R. Lian, et al., “Supramolecular Host:Guest Arrays Site-Selectively Recognize Peptide Phosphorylation and Kinase Activity,” Journal of the American Chemical Society 147 (2025): 841–850.

[159] J. Chen, B. L. Hickey, L. Wang, et al., “Selective Discrimination and Classification of G-quadruplex Structures With a Host–Guest Sensing Array,” Nature Chemistry 13 (2021): 488–495.

[160] J. Chen, A. D. Gill, B. L. Hickey, et al., “Machine Learning Aids Classification and Discrimination of Noncanonical DNA Folding Motifs by an Arrayed Host:Guest Sensing System,” Journal of the American Chemical Society 143 (2021): 12791–12799.

[161] J. Chen, B. L. Hickey, Z. Gao, A. A. P. Raz, R. J. Hooley, and W. Zhong, “Sensing Base Modifications in Non-Canonically Folded DNA With an Optimized Host:Guest Sensing Array,” ACS Sensors 7 (2022): 2164–2169.

[162] R. Lian, Y. D. Yang, J. L. Moreno, et al., “Self-Aggregative Recognition and Extraction of Perfluorooctanesulfonate With Flexible Cationic Water-Soluble Deep Cavitands,” Journal of the American Chemical Society 147 (2025): 22768–22777.

[163] Y. Liu, J. Lee, L. Perez, A. D. Gill, R. J. Hooley, and W. Zhong, “Selective Sensing of Phosphorylated Peptides and Monitoring Kinase and Phosphatase Activity With a Supramolecular Tandem Assay,” Journal of the American Chemical Society 140 (2018): 13869–13877.

[164] A. D. Gill, B. L. Hickey, S. Wang, M. Xue, W. Zhong, and R. J. Hooley, “Sensing of Citrulline Modifications in Histone Peptides by Deep cavitand Hosts,” Chemical Communications 55 (2019): 13259–13262.

[165] Y. Liu, Y. Duan, A. D. Gill, et al., “Metal-assisted Selective Recognition of Biothiols by a Synthetic Receptor Array,” Chemical Communications 54 (2018): 13147–13150.

[166] A. D. Gill, L. Perez, I. N. Q. Salinas, et al., “Selective Array-Based Sensing of Anabolic Steroids in Aqueous Solution by Host–Guest Reporter Complexes,” Chemistry – A European Journal 25 (2019): 1740–1745.

[167] R. M. Webster, “Combination Therapies in Oncology,” Nature Reviews Drug Discovery 15 (2016): 81–82.

[168] A. Detappe, H. V. T. Nguyen, Y. Jiang, et al., “Molecular Bottlebrush Prodrugs as Mono- and Triplex Combination Therapies for Multiple Myeloma,” Nature Nanotechnology 18 (2023): 184–192.

[169] M. Ahn, T. Lee, K. S. Kim, S. Lee, and K. Na, “Synergistic Approach of Antibody-Photosensitizer Conjugate Independent of KRAS-Mutation and Its Downstream Blockade Pathway in Colorectal Cancer,” Advanced Healthcare Materials 12 (2023): 2302374.

[170] Y. Liu, L. Tong, M. Zhang, et al., “A Novel Strategy for Treating Oncogene-Mutated Tumors by Targeting Tumor Microenvironment and Synergistically Enhancing Anti-PD-1 Immunotherapy,” Cancer Communications 44 (2024): 438–442.

[171] J. Kim, S. Lee, Y. Kim, et al., “In Situ Self-assembly for Cancer Therapy and Imaging,” Nature Reviews Materials 8 (2023): 710–725.

[172] M. Yan, S. Wu, Y. Wang, et al., “Recent Progress of Supramolecular Chemotherapy Based on Host–Guest Interactions,” Advanced Materials 36 (2024): 2304249.

[173] W. C. Geng, J. L. Sessler, and D. S. Guo, “Supramolecular Prodrugs Based on Host–Guest Interactions,” Chemical Society Reviews 49 (2020): 2303–2315.

[174] J. Tian, F. Lin, S. B. Yu, J. Yu, Q. Tang, and Z. T. Li, “Water-Dispersible and Soluble Porous Organic Polymers for Biomedical Applications,” Aggregate 3 (2022): e187.

[175] M. M. Chen, Y. Q. Li, Y. J. Zhu, et al., “Supramolecular 3 in 1: A Lubrication and Co-Delivery System for Synergistic Advanced Osteoarthritis Therapy,” ACS Nano 18 (2024): 13117–13129. 20.

[176] H. Sun, S. K. Li, Q. Liu, et al., “Supramolecular Prodrug Vesicles for Selective Antimicrobial Therapy Employing a Chemo-photodynamic Strategy,” Chinese Chemical Letters 36 (2025): 109999.

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