Citation: Yan-Fang Wang, Jia Liu, Wei Li, Song-Meng Wang, Jian Qin, Cheng-Da Zhao, Liu-Pan Yang, Li-Li Wang. Hybridtube with endo-functionalized cavity for highly selective recognition: Subtle structure changes in guest lead to significant binding affinity variations[J]. Chinese Chemical Letters, ;2026, 37(6): 112368. doi: 10.1016/j.cclet.2026.112368 shu

Hybridtube with endo-functionalized cavity for highly selective recognition: Subtle structure changes in guest lead to significant binding affinity variations

Yan-Fang Wang ^{a, b, 1} ,
Jia Liu ^{a, 1} ,
Wei Li ^{a, 1} ,
Song-Meng Wang ^a ,
Jian Qin ^a ,
Cheng-Da Zhao ^{a, *,} ,
Liu-Pan Yang ^{a, *,} ,
Li-Li Wang ^{a, *,}

a.
The Affiliated Nanhua Hospital, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, China
b.
Department of Chemistry, Zhejiang University, Hangzhou 310058, China

zcd880413@163.com

yanglp@usc.edu.cn

wangll@usc.edu.cn

Received Date: 10 November 2025
Revised Date: 25 December 2025
Accepted Date: 4 January 2026
Available Online: 6 January 2026

Figures(5)

Achieving highly selective recognition of structurally similar substrates in water has been, and still remains, challenging. Herein, we report highly selective recognition of adenosine (A) and its analogs by using a hybridtube (HT) with endo-functionalized cavity. Fluorescence titration data and density-functional theory calculations reveal that the macrocycle's hydrophobic cavity and its internal hydrogen-bonding sites are crucial for attaining this high binding selectivity to A and its analogs. Decreasing the number of hydrophilic hydroxyl groups on the ribose ring while increasing the number of hydrophobic methyl groups on the purine ring can significantly enhance the hydrophobic effect between host and guest, thereby strengthening the binding affinity. Furthermore, different hydrogen bond acceptors on the guest can greatly affect host-guest binding, leading to a substantial enhancement in binding selectivity (A/dA up to 61.7-fold). Based on the high binding selectivity of HT, a substrate-selective fluorescent supramolecular tandem assay was developed for real-time and continuous monitoring of the enzyme activity of adenosine deaminase (ADA). Finally, we demonstrated the potential of this tandem assay for inhibitor screening, which holds significant implications for drug design and medical diagnostics.
- Biomimetic macrocycle,
- Molecular recognition,
- Selectivity,
- Enzyme assay
1. [1]
  E. Persch, O. Dumele, F. Diederich, Angew. Chem. Int. Ed. 54 (2015) 3290–3327. doi: 10.1002/anie.201408487
2. [2]
  J.L. Hu, X.X. Xu, L.Q. Liu, et al., Adv. Healthcare. Mater. 14 (2025) 2404569. doi: 10.1002/adhm.202404569
3. [3]
  W.W. Kung, S. Ramachandran, N. Makukhin, et al., Nat. Commun. 10 (2019) 2534. doi: 10.1038/s41467-019-10190-4
4. [4]
  Q.S. Ji, Y.R. Liu, H.Y. Zhang, et al., Adv. Sci. 12 (2025) 2413185. doi: 10.1002/advs.202413185
5. [5]
  P.S. Cremer, A.H. Flood, B.C. Gibb, D.L. Mobley, Nat. Chem. 10 (2017) 8–16.
6. [6]
  R.W. Tang, Y.P. Ye, S.J. Zhu, et al., Chin. Chem. Lett. 34 (2023) 107734. doi: 10.1016/j.cclet.2022.08.014
7. [7]
  F.Y. Chen, R. Fu, Z.H. Gong, et al., Angew. Chem. Int. Ed. 64 (2025) e202500916. doi: 10.1002/anie.202500916
8. [8]
  L. Adriaenssens, P. Ballester, Chem. Soc. Rev. 42 (2013) 3261–3277. doi: 10.1039/c2cs35461f
9. [9]
  C.D. Zhao, H. Yao, S.Y. Li, et al., Chin. Chem. Lett. 35 (2024) 108879. doi: 10.1016/j.cclet.2023.108879
10. [10]
  J. Liu, L.H. Yi, Y.X. He, et al., Microchem. J. 217 (2025) 114878. doi: 10.1016/j.microc.2025.114878
11. [11]
  D. Hernández-Alonso, S. Zankowski, L. Adriaenssens, P. Ballester, Org. Biomol. Chem. 13 (2015) 1022–1029. doi: 10.1039/C4OB02108H
12. [12]
  B. Verdejo, G. Gil-Ramirez, P. Ballester, J. Am. Chem. Soc. 131 (2009) 3178–3179. doi: 10.1021/ja900151u
13. [13]
  R.A. Tromans, S.K. Samanta, A.M. Chapman, A.P. Davis, Chem. Sci. 11 (2020) 3223–3227. doi: 10.1039/c9sc05406e
14. [14]
  G.B. Huang, S.H. Wang, H. Ke, et al., J. Am. Chem. Soc. 138 (2016) 14550–14553. doi: 10.1021/jacs.6b09472
15. [15]
  H. Yao, H. Ke, X.B. Zhang, et al., J. Am. Chem. Soc. 140 (2018) 13466–13477. doi: 10.1021/jacs.8b09157
16. [16]
  X. Huang, X.P. Wang, M. Quan, et al., Angew. Chem. Int. Ed. 60 (2021) 1929–1935. doi: 10.1002/anie.202012467
17. [17]
  X.P. Wang, M. Quan, H. Yao, et al., Nat. Commun. 13 (2022) 2291. doi: 10.24963/ijcai.2022/318
18. [18]
  H. Zhou, X.Y. Pang, X.P. Wang, et al., Angew. Chem. Int. Ed. 60 (2021) 25981–25987. doi: 10.1002/anie.202112267
19. [19]
  S.M. Wang, H. Nian, Y.F. Wang, et al., Sci. China Chem. 68 (2024) 369–376.
20. [20]
  A.G. Johnston, D.A. Leigh, A. Murphy, et al., J. Am. Chem. Soc. 118 (1996) 10662–10663. doi: 10.1021/ja962046r
21. [21]
  W. Liu, A.G. Oliver, B.D. Smith, J. Am. Chem. Soc. 140 (2018) 6810–6813. doi: 10.1021/jacs.8b04155
22. [22]
  H. Yao, J. Qin, Y.F. Wang, et al., Chin. Chem. Lett. 35 (2024) 109154. doi: 10.1016/j.cclet.2023.109154
23. [23]
  S.Y. Li, H. Yao, H. Hu, et al., Chem. Commun. 59 (2023) 7204–7207. doi: 10.1039/d3cc01164j
24. [24]
  Y. Qiu, S. Yu, S.M. Wang, et al., Chem. Eng. J. 495 (2024) 153143. doi: 10.1016/j.cej.2024.153143
25. [25]
  H. Yao, S.Y. Li, H. Zhang, et al., Chem. Commun. 59 (2023) 5411–5414. doi: 10.1039/d2cc06622j
26. [26]
  Y.F. Wang, S.M. Wang, X.B. Zhang, et al., Angew. Chem. Int. Ed. 62 (2023) e202310115. doi: 10.1002/anie.202310115
27. [27]
  G.G. Yegutkin, D. Boison, Pharmacol. Rev. 74 (2022) 797–822.
28. [28]
  S. Man, Y.Y. Lu, L.J. Yin, et al., Drug Discov. Today 26 (2021) 1490–1500. doi: 10.1016/j.drudis.2021.02.020
29. [29]
  X. Gong, B. Tang, J.J. Liu, et al., Biosens. Bioelectron. 87 (2017) 858–864. doi: 10.1016/j.bios.2016.09.027
30. [30]
  P. Wang, J.X. Liu, Y. Ma, et al., Chem. Eng. J. 394 (2020) 124931. doi: 10.1016/j.cej.2020.124931
31. [31]
  Y.Q. Li, Z.J. Zhang, B.W. Liu, J.W. Liu, ACS Appl. Bio. Mater. 3 (2020) 2568–2576. doi: 10.1021/acsabm.9b00936
32. [32]
  H. Yao, Z.P. Xiao, J. Guo, et al., Sci. China Chem. 68 (2025) 4264–4275. doi: 10.1007/s11426-025-2771-7
33. [33]
  A.A. Dewantari, N. Yongwattana, P. Payongsri, et al., Molecules 25 (2020) 2045. doi: 10.3390/molecules25092045
34. [34]
  T.X. Xiang, B.D. Anderson, Int. J. Pharm. 59 (1990) 45–55. doi: 10.1016/0378-5173(90)90063-A
35. [35]
  J.C. Kromann, C. Steinmann, J.H. Jensen, J. Chem. Phys. 149 (2018) 104102. doi: 10.1063/1.5047273
36. [36]
  T. Lu, F.W. Chen, J. Comput. Chem. 33 (2012) 580–592. doi: 10.1002/jcc.22885
37. [37]
  N.H. Elowe, R. Nutiu, A. Allali-Hassani, et al., Angew. Chem. Int. Ed. 45 (2006) 5648–5652. doi: 10.1002/anie.200601695
38. [38]
  X.J. Xing, X.G. Liu, Y. He, et al., Biosens. Bioelectron. 37 (2012) 61–67. doi: 10.1016/j.bios.2012.04.037
39. [39]
  A. Aiuti, M.G. Roncarolo, L. Naldini, EMBO. Mol. Med. 9 (2017) 737–740. doi: 10.15252/emmm.201707573
40. [40]
  E. Grunebaum, C. Booth, G.D.E. Cuvelier, et al., J. Allergy. Clin. Immunol. Pract. 11 (2023) 1665–1675.
41. [41]
  M. Migliavacca, F. Barzaghi, C. Fossati, et al., Nat. Med. 30 (2024) 488–497. doi: 10.1038/s41591-023-02789-4
42. [42]
  B. Reinhardt, O. Habib, K.L. Shaw, et al., Blood 138 (2021) 1304–1316. doi: 10.1182/blood.2020010260
43. [43]
  V.H.D. Kim, A. Pham-Huy, E. Grunebaum, J. Allergy. Clin. Immunol. 143 (2019) 403–405. doi: 10.1016/j.jaci.2018.04.029
44. [44]
  A. Pormohammad, S.M. Riahi, M.J. Nasiri, et al., J. Infect. 74 (2017) 545–554.
45. [45]
  B. Kutryb-Zajac, L. Mateuszuk, P. Zukowska, et al., Cardiovasc. Res. 112 (2016) 590–605. doi: 10.1093/cvr/cvw203
46. [46]
  Z.W. Gao, X. Wang, H.Z. Zhang, et al., Autoimmun. Rev. 20 (2021) 102709.
47. [47]
  J. Lu, D.G. Grenache, Clin. Chim. Acta 413 (2012) 1637–1640.
48. [48]
  L. Silva Dalsasso Joaquim, N. Granzotto, L.F. Dos Santos, et al., J. Clin. Lab. Anal. 33 (2019) e22823.
49. [49]
  H. Ni, Y.H. Li, R.L. Hao, et al., Int. J. Food Sci. Tech. 51 (2016) 1168–1176. doi: 10.1111/ijfs.13064
50. [50]
  Y.F. Qi, Y.X. Li, J.J. Bao, Anal. Biochem. 506 (2016) 31–44.
51. [51]
  J.H. Zhu, L.P. Mei, A.J. Wang, et al., Biosens. Bioelectron. 226 (2023) 115141.
52. [52]
  P.T. Lin, S.L. Zhao, X. Lu, et al., J. Sep. Sci. 36 (2013) 2538–2543. doi: 10.1002/jssc.201300315
53. [53]
  L. Pei, L.J. Xie, Q. Lin, et al., Anal. Biochem. 414 (2011) 131–137.
54. [54]
  S.L. Qi, H.D. Guan, G. Deng, et al., J. Pharm. Biomed. Anal. 153 (2018) 175–181.
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