Chiral Self-Sorting of Flexible Covalent Organic Pillars for Adaptive Molecular Recognition
Dr. Shengnan Gao
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
Both authors contributed equally to this work.
Search for more papers by this authorMin Zhang
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
Both authors contributed equally to this work.
Search for more papers by this authorYimin Zhang
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
Search for more papers by this authorDr. Congsen Wang
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
Search for more papers by this authorCorresponding Author
Prof. Andrew C.-H. Sue
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
E-mail: [email protected]
Search for more papers by this authorDr. Shengnan Gao
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
Both authors contributed equally to this work.
Search for more papers by this authorMin Zhang
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
Both authors contributed equally to this work.
Search for more papers by this authorYimin Zhang
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
Search for more papers by this authorDr. Congsen Wang
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
Search for more papers by this authorCorresponding Author
Prof. Andrew C.-H. Sue
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) and College of Chemistry and Chemical Engineering, Xiamen University, 422 Siming South Road, Siming District, Xiamen, 361005 P.R. China
E-mail: [email protected]
Search for more papers by this authorDedicated to Prof. Wen-Sheng Chung on the occasion of his 65th birthday
Graphical Abstract
Flexible covalent organic pillars (flex-COP-n) are adaptive nanotubular hosts formed via dynamic imine condensation. Their self-assembly displays an odd–even effect, yielding enantiomeric or meso duplexes. Host–guest studies reveal binding modes shaped by mutual deformation and geometric complementarity, underscoring their capacity for responsive molecular recognition.
Abstract
Flexible covalent organic pillars (flex-COP-n) are introduced as a family of dual-open-ended nanotubular hosts constructed via dynamic imine condensation between pillararene-derived macrocyclic building blocks and conformationally mobile ─(CH2)n─ aliphatic linkers. These discrete molecular containers feature well-defined tubular channels capable of adaptive host–guest interactions. The self-assembly process exhibits a pronounced odd–even effect, yielding either enantiomeric or meso duplexes through distinct chiral self-sorting pathways. Host–guest interactions between flex-COP-4 and a series of α,ω-dibromoalkanes were systematically investigated using NMR spectroscopy and single-crystal X-ray crystallography. The resulting inclusion complexes span a continuum of binding modes—from relaxed encapsulation to strained, overpacked assemblies—governed by geometric complementarity and mutual host–guest deformation. These findings highlight the role of conformational flexibility in modulating molecular recognition under nanoscale confinement and establish flex-COP-n as a dynamic platform for mimicking adaptive features of biological receptors.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request. The X-ray crystallographic data reported in this work have been deposited at the Cambridge Crystallographic Data Centre.69
Supporting Information
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References
- 1J.-M. Lehn, Molecular Recognition in Supramolecular Chemistry, VCH, Weinheim, Germany 1995, pp. 11–30.
10.1002/3527607439.ch2 Google Scholar
- 2D. J. Cram, Nature 1992, 356, 29–36.
- 3J. Rebek, Jr., Acc. Chem. Res. 2009, 42, 1660–1668.
- 4D. Ajami, J. Rebek, Jr., Acc. Chem. Res. 2013, 46, 990–999.
- 5L. Trembleau, J. Rebek, Jr., Science 2003, 301, 1219–1220.
- 6A. B. Grommet, M. Feller, R. Klajn, Nat. Nanotechnol. 2020, 15, 256–271.
- 7W. Liu, J. F. Stoddart, Chem 2021, 7, 919–947.
- 8D. J. Cram, Science 1988, 240, 760–767.
- 9D. J. Cram, Angew. Chem. Int. Ed. Engl. 1988, 27, 1009–1020.
- 10D. J. Cram, J. M. Cram, in Container Molecules and Their Guests (Ed: J. Fraser Stoddart), The Royal Society of Chemistry, Cambridge, U.K. 1997.
10.1039/9781847550620 Google Scholar
- 11J. B. Wittenberg, L. Isaacs, Complementarity and Preorganization in Supramolecular Chemistry, John Wiley & Sons, Ltd., Hoboken, NJ 2012.
- 12E. Fischer, Ber. Dtsch. Chem. Ges. 1894, 27, 2985–2993.
- 13D. E. Koshland Jr., Angew. Chem. Int. Ed. Engl. 1995, 33, 2375–2378.
- 14P. Csermely, R. Palotai, R. Nussinov, Trends Biochem. Sci. 2010, 35, 539–546.
- 15L. Fielding, S. Rutherford, D. Fletcher, Magn. Reson. Chem. 2005, 43, 463–470.
- 16L. Fielding, Prog. Nucl. Magn. Reson. Spectrosc. 2007, 51, 219–242.
- 17G. Crini, Chem. Rev. 2014, 114, 10940–10975.
- 18J. Lagona, P. Mukhopadhyay, S. Chakrabarti, L. Isaacs, Angew. Chem. Int. Ed. 2005, 44, 4844–4870.
- 19C. D. Gutsche, Calixarenes Revisited, The Royal Society of Chemistry, Cambridge, U.K. 1998, p. 248.
10.1039/9781847550293 Google Scholar
- 20J. L. S. Placido Neri, Mei-Xiang Wang, Calixarenes and Beyond, Springer, Cham, Switzerland 2016.
10.1007/978-3-319-31867-7 Google Scholar
- 21 Pillararenes (Ed: T. Ogoshi), The Royal Society of Chemistry, Cambridge, U.K. 2015.
10.1039/9781782622321 Google Scholar
- 22W. Zhang, J. S. Moore, Angew. Chem. Int. Ed. 2006, 45, 4416–4439.
- 23E. J. Dale, N. A. Vermeulen, M. Juríček, J. C. Barnes, R. M. Young, M. R. Wasielewski, J. F. Stoddart, Acc. Chem. Res. 2016, 49, 262–273.
- 24Z. Liu, S. K. M. Nalluri, J. F. Stoddart, Chem. Soc. Rev. 2017, 46, 2459–2478.
- 25Y. Wang, H. Wu, J. F. Stoddart, Acc. Chem. Res. 2021, 54, 2027–2039.
- 26A. Collet, Tetrahedron 1987, 43, 5725–5759.
- 27K. Kobayashi, M. Yamanaka, Chem. Soc. Rev. 2015, 44, 449–466.
- 28M. Fujita, M. Tominaga, A. Hori, B. Therrien, Acc. Chem. Res. 2005, 38, 369–378.
- 29M. Yoshizawa, J. K. Klosterman, M. Fujita, Angew. Chem. Int. Ed. 2009, 48, 3418–3438.
- 30M. Yoshizawa, M. Fujita, Bull. Chem. Soc. Jpn. 2010, 83, 609–618.
- 31T. Tozawa, J. T. A. Jones, S. I. Swamy, S. Jiang, D. J. Adams, S. Shakespeare, R. Clowes, D. Bradshaw, T. Hasell, S. Y. Chong, C. Tang, S. Thompson, J. Parker, A. Trewin, J. Bacsa, A. M. Z. Slawin, A. Steiner, A. I. Cooper, Nat. Mater. 2009, 8, 973–978.
- 32T. Hasell, A. I. Cooper, Nat. Rev. Mater. 2016, 1, 16053.
- 33A. I. Cooper, ACS Central Sci. 2017, 3, 544–553.
- 34X. Yang, Z. Ullah, J. F. Stoddart, C. T. Yavuz, Chem. Rev. 2023, 123, 4602–4634.
- 35J. R. Nitschke, Acc. Chem. Res. 2007, 40, 103–112.
- 36E. G. Percástegui, T. K. Ronson, J. R. Nitschke, Chem. Rev. 2020, 120, 13480–13544.
- 37C. T. McTernan, J. A. Davies, J. R. Nitschke, Chem. Rev. 2022, 122, 10393–10437.
- 38J. J. Henkelis, M. J. Hardie, Chem. Commun. 2015, 51, 11929–11943.
- 39H. Hou, Z. Jiang, Q. Chen, Q.-F. Sun, M. Hong, CCS Chem. 2025, 7, 1–16. https://doi.org/10.31635/ccschem.025.202505454.
- 40O. Taratula, P. A. Hill, N. S. Khan, P. J. Carroll, I. J. Dmochowski, Nat. Commun. 2010, 1, 148.
- 41D.-W. Zhang, X. Zhao, Z.-T. Li, Acc. Chem. Res. 2014, 47, 1961–1970.
- 42M. Zhang, X. Yan, F. Huang, Z. Niu, H. W. Gibson, Acc. Chem. Res. 2014, 47, 1995–2005.
- 43D.-H. Qu, Q.-C. Wang, Q.-W. Zhang, X. Ma, H. Tian, Chem. Rev. 2015, 115, 7543–7588.
- 44C. M. Hong, D. M. Kaphan, R. G. Bergman, K. N. Raymond, F. D. Toste, J. Am. Chem. Soc. 2017, 139, 8013–8021.
- 45Y. Tamura, H. Takezawa, M. Fujita, J. Am. Chem. Soc. 2020, 142, 5504–5508.
- 46K. Artmann, R.-J. Li, S. Juber, E. Benchimol, L. V. Schäfer, G. H. Clever, P. Nuernberger, Angew. Chem. Int. Ed. 2022, 61, e202212112.
- 47B. Huang, S. Li, C. Pan, F. Li, L. Wojtas, Q. Qiao, T. H. Tran, L. Calcul, W. Liu, C. Ke, J. Cai, Nat. Commun. 2025, 16, 3226.
- 48H. Xu, T. K. Ronson, A. W. Heard, P. C. P. Teeuwen, L. Schneider, P. Pracht, J. D. Thoburn, D. J. Wales, J. R. Nitschke, Nat. Chem. 2025, 17, 289–296.
- 49A. P. Gia, A. de Juan, D. Aranda, F. G. Guijarro, J. Aragó, E. Ortí, M. García-Iglesias, D. González-Rodríguez, J. Am. Chem. Soc. 2025, 147, 918–931.
- 50Y. Tian, Y. Guo, X. Dong, X. Wan, K.-H. Cheng, R. Chang, S. Li, X. Cao, Y.-T. Chan, A. C.-H. Sue, Nat. Synth. 2023, 2, 395–402.
- 51M. Zhang, S. Gao, X. Dong, A. C.-H. Sue, Tetrahedron Lett. 2023, 126, 154642.
- 52S. Gao, Y. Guo, J. Xue, X. Dong, X.-Y. Cao, A. C.-H. Sue, J. Am. Chem. Soc. 2024, 146, 20963–20971.
- 53T. Ogoshi, S. Kanai, S. Fujinami, T.-a. Yamagishi, Y. Nakamoto, J. Am. Chem. Soc. 2008, 130, 5022–5023.
- 54T. Ogoshi, T.-a. Yamagishi, Y. Nakamoto, Chem. Rev. 2016, 116, 7937–8002.
- 55K. Kato, S. Fa, S. Ohtani, T.-h. Shi, A. M. Brouwer, T. Ogoshi, Chem. Soc. Rev. 2022, 51, 3648–3687.
- 56M. Guo, X. Wang, C. Zhan, P. Demay-Drouhard, W. Li, K. Du, M. A. Olson, H. Zuilhof, A. C.-H. Sue, J. Am. Chem. Soc. 2018, 140, 74–77.
- 57P. Demay-Drouhard, K. Du, K. Samanta, X. Wan, W. Yang, R. Srinivasan, A. C.-H. Sue, H. Zuilhof, Org. Lett. 2019, 21, 3976–3980.
- 58W. Yang, K. Samanta, X. Wan, T. U. Thikekar, Y. Chao, S. Li, K. Du, J. Xu, Y. Gao, H. Zuilhof, A. C.-H. Sue, Angew. Chem. Int. Ed. 2020, 59, 3994–3999.
- 59Y. Chao, T. U. Thikekar, W. Fang, R. Chang, J. Xu, N. Ouyang, J. Xu, Y. Gao, M. Guo, H. Zuilhof, A. C.-H. Sue, Angew. Chem. Int. Ed. 2022, 61, e202204589.
- 60The methylene bridge (─CH2─) protons are chemically non-equivalent but appear isochronous in the 1H NMR spectrum. Aside from a singlet-like signal, only very weak fine structure is observed.
- 61S. Bera, A. Basu, S. Tothadi, B. Garai, S. Banerjee, K. Vanka, R. Banerjee, Angew. Chem. Int. Ed. 2017, 56, 2123–2126.
- 62K. Su, W. Wang, S. Du, C. Ji, M. Zhou, D. Yuan, J. Am. Chem. Soc. 2020, 142, 18060–18072.
- 63K. Koner, A. Sadhukhan, S. Karak, H. S. Sasmal, Y. Ogaeri, Y. Nishiyama, S. Zhao, M. Položij, A. Kuc, T. Heine, R. Banerjee, J. Am. Chem. Soc. 2023, 145, 14475–14483.
- 64K. Du, P. Demay-Drouhard, K. Samanta, S. Li, T. U. Thikekar, H. Wang, M. Guo, B. van Lagen, H. Zuilhof, A. C.-H. Sue, J. Org. Chem. 2020, 85, 11368–11374.
- 65H. Jędrzejewska, A. Szumna, Chem. Rev. 2017, 117, 4863–4899.
- 66D. Beaudoin, F. Rominger, M. Mastalerz, Angew. Chem. Int. Ed. 2017, 56, 1244–1248.
- 67P. Wagner, F. Rominger, W.-S. Zhang, J. H. Gross, S. M. Elbert, R. R. Schröder, M. Mastalerz, Angew. Chem. Int. Ed. 2021, 60, 8896–8904.
- 68S. Mecozzi, J. Rebek, Jr., Chem. - Eur. J. 1998, 4, 1016–1022.
10.1002/(SICI)1521-3765(19980615)4:6<1016::AID-CHEM1016>3.0.CO;2-B CAS Web of Science® Google Scholar
- 69Deposition numbers 2444132 (for [Br(CH2)12Br⊂(M)-flex-COP-4]), 2444133 (for [Br(CH2)13Br⊂(M)-flex-COP-4]), 2444134 (for [Br(CH2)10Br⊂(P)-flex-COP-4]), 2444135 (for [Br(CH2)15Br⊂(M)-flex-COP-4]), 2444136 (for [Br(CH2)11Br⊂(P)-flex-COP-4]), 2444137 (for [Br(CH2)12Br⊂(rac)-flex-COP-4]), 2444138 (for [Br(CH2)18Br⊂(rac)-flex-COP-4]), 2444139 (for [Br(CH2)12Br⊂(rac)-flex-COP-2]), 2444140 (for [Br(CH2)12Br⊂flex-COP-3]), 2444141 (for [Br(CH2)16Br⊂(rac)-flex-COP-4]), 2444145 (for [Br(CH2)14Br⊂(M)-flex-COP-4]), 2444146 (for [3·CH2Cl2⊂(rac)-flex-COP-2]), 2444147 (for [Br(CH2)10Br⊂flex-COP-3]), 2444148 (for [4·CH2Cl2⊂(rac)-flex-COP-4]), 2444149 (for [Br(CH2)15Br⊂flex-COP-3]), 2444151 (for [Br(CH2)12Br⊂flex-COP-5]), 2444152 (for [2·CHCl3·2·MeCN⊂(rac)-flex-COP-4]), 2444153 (for [4·CH2Cl2⊂(M)-flex-COP-4]), 2444154 (for [Br(CH2)9Br⊂flex-COP-3]), 2444155 (for [Br(CH2)18Br⊂(rac)-flex-COP-6]) and 2444156 (for [Br(CH2)18Br⊂flex-COP-5]) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe http://www.ccdc.cam.ac.uk/structures service.
