Citation: Yao Zou, Difei Gong, Haiguang Yang, Hongmei Yu, Guorong He, Ningbo Gong, Lianhua Fang, Guanhua Du, Yang Lu. Prediction, screening, characterization, antioxidant and antihypoxic effects of multi-component zwitterionic cocrystals of dietary flavonoids with picolinic acid[J]. Chinese Chemical Letters, ;2025, 36(9): 110768. doi: 10.1016/j.cclet.2024.110768 shu

Prediction, screening, characterization, antioxidant and antihypoxic effects of multi-component zwitterionic cocrystals of dietary flavonoids with picolinic acid

Yao Zou ^{a, 1} ,
Difei Gong ^{b, 1} ,
Haiguang Yang ^b ,
Hongmei Yu ^a ,
Guorong He ^b ,
Ningbo Gong ^{a, *,} ,
Lianhua Fang ^{b, *,} ,
Guanhua Du ^b ,
Yang Lu ^{a, *,}

a.
Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
Beijing City Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

gnb@imm.ac.cn

fanglh@imm.ac.cn

luy@imm.ac.cn

Received Date: 3 June 2024
Revised Date: 22 October 2024
Accepted Date: 13 December 2024
Available Online: 14 December 2024

Figures(9)

The objective of this study was to predict, screen, synthesize, and investigate cocrystals of poorly soluble flavonoids that are commonly found in dietary supplements with bipolar compound picolinic acid (PA). To improve the efficiency and success rate of experimental screening, two virtual tools based on hydrogen bond propensity (HBP) and modified molecular electrostatic potential (MEP) maps were used. The prediction accuracy of HBP and MEP is 58.82% and 94.11%, respectively, presenting that the MEP model is very powerful in the discovery of pharmaceutical cocrystals. Among the 12 successfully obtained cocrystals, 4 single crystals of PA with luteolin (LUT), genistein (GEN), taxifolin (TAX), dihydromyricetin (DHM) were obtained for the first time. Charged-assisted OH···O and NH···O hydrogen bonds appear as main hydrogen bonding synthons, and PA adopts a zwitterionic form after cocrystallization. GEN-PA, TAX-PA, and DHM-PA showed higher DPPH^• radical-scavenging capacities; LUT-PA and DHM-PA showed higher ABTS⁺ radical-scavenging capacities; GEN-PA and DHM-PA possessed better protective effects on H9c2 cells from hypoxic injury caused by CoCl₂ than corresponding pure flavonoids.
- Cocrystal,
- Flavonoid,
- Picolinic acid,
- Dietary supplements,
- Zwitterionic
1. [1]
  M. Fardoun, D. Maaliki, N. Halabi, et al., Clin. Sci. 134 (2020) 1403–1432. doi: 10.1042/cs20200356
2. [2]
  J. Melrose, Antioxidants 12 (2023) 663. doi: 10.3390/antiox12030663
3. [3]
  K.R. Surana, E.D. Ahire, S.K. Mahajan, et al., Antimicrobial and antiinflammatory action of flavonoids, in: J.B. Harborne, T.J. Mabry, H. Mabry (Eds.), The Flavonoids, Apple Academic Press, Palm Bay Florida, 2024, pp. 263–276.
4. [4]
  Z. Wang, L. Yang, Nutrients 15 (2023) 3443. doi: 10.3390/nu15153443
5. [5]
  M. Park, D. Ryu, J. Cho, et al., Molecules 29 (2024) 283. doi: 10.3390/molecules29020283
6. [6]
  J. Sharifi-Rad, C. Quispe, S. Shaheen, et al., Crit. Rev. Food Sci. Nutr. 62 (2022) 8045–8058. doi: 10.1080/10408398.2021.1924612
7. [7]
  V. Kesharwani, S. Kabra, B.C. Semwal, et al., Neuroprotective effects of flavonoids, in: N. Sharma, D. Saini, R.K. Kesharani, et al. (Eds.), Advances in Flavonoids for Human Health and Prevention of Diseases, Apple Academic Press, Palm Bay Florida, 2024, pp. 95–123.
8. [8]
  Y. Wang, Y. Mou, S. Lu, et al., PeerJ 12 (2024) e16711. doi: 10.7717/peerj.16711
9. [9]
  T.P. Lam, N.V.N. Tran, L.H.D. Pham, et al., Nat. Prod. Bioprospect. 14 (2024) 4. doi: 10.1007/s13659-023-00424-w
10. [10]
  D. Yuan, Y. Guo, F. Pu, et al., Food Chem. 430 (2023) 137115.
11. [11]
  J. Zhao, J. Yang, Y. Xie, Int. J. Pharm. 570 (2019) 118642. doi: 10.1016/j.ijpharm.2019.118642
12. [12]
  E. Ban, S.H. An, B. Park, et al., J. Pharm. Sci. 109 (2020) 3660–3667. doi: 10.1016/j.xphs.2020.09.030
13. [13]
  G. Bolla, A. Nangia, Chem. Commun. 52 (2016) 8342–8360. doi: 10.1039/C6CC02943D
14. [14]
  B. Lu, S. Liu, D. Yan, Chin. Chem. Lett. 30 (2019) 1908–1922. doi: 10.1016/j.cclet.2019.09.012
15. [15]
  S. Li, Y. Lin, D. Yan, J. Mater. Chem. C 4 (2016) 2527–2534. doi: 10.1039/C6TC00067C
16. [16]
  C. Xing, B. Zhou, D. Yan, et al., CCS Chem. 5 (2023) 2866–2876. doi: 10.31635/ccschem.023.202202605
17. [17]
  C. Xing, Z. Qi, B. Zhou, et al., Angew. Chem. Int. Ed. 63 (2024) e202402634. doi: 10.1002/anie.202402634
18. [18]
  D. Yan, A. Delori, G.O. Lloyd, et al., Angew. Chem. Int. Ed. 50 (2011) 12483–12486. doi: 10.1002/anie.201106391
19. [19]
  D. Yan, Chem. Eur. J. 21 (2015) 4880–4896. doi: 10.1002/chem.201405456
20. [20]
  S. Li, B. Lu, X. Fang, et al., Angew. Chem. Int. Ed. 59 (2020) 22623–22630. doi: 10.1002/anie.202009714
21. [21]
  X.G. Yang, Z.M. Zhai, X.M. Lu, et al., ACS Cent. Sci. 6 (2020) 1169–1178. doi: 10.1021/acscentsci.0c00447
22. [22]
  J. Xu, Q. Shi, Y. Wang, et al., Molecules 28 (2023) 613. doi: 10.3390/molecules28020613
23. [23]
  X. Jia, H. Hao, Q. Zhang, et al., Phytomedicine 122 (2024) 155179. doi: 10.1016/j.phymed.2023.155179
24. [24]
  M.K. Bommaka, M.K.C. Mannava, K. Suresh, et al., Cryst. Growth Des. 18 (2018) 6061–6069. doi: 10.1021/acs.cgd.8b00921
25. [25]
  C. Almansa, R. Merce, N. Tesson, et al., Cryst. Growth Des. 17 (2017) 1884–1892. doi: 10.1021/acs.cgd.6b01848
26. [26]
  Y. Deng, Y. Zhang, Y. Huang, et al., Cryst. Growth Des. 18 (2018) 7481–7488. doi: 10.1021/acs.cgd.8b01257
27. [27]
  N.K. Duggirala, M.L. Perry, Ö. Almarsson, et al., Chem. Commun. 52 (2016) 640–655. doi: 10.1039/C5CC08216A
28. [28]
  J. Yao, J.M. Chen, Y.B. Xu, et al., Cryst. Growth Des. 14 (2014) 5019–5025. doi: 10.1021/cg5005819
29. [29]
  A. Tilborg, G. Springuel, B. Norberg, et al., CrystEngComm 15 (2013) 3341–3350. doi: 10.1039/c3ce40084k
30. [30]
  L.L. Wang, L.Y. Wang, Y.M. Yu, et al., CrystEngComm 22 (2020) 5010–5021. doi: 10.1039/D0CE00713G
31. [31]
  A. Gunnam, K. Suresh, R. Ganduri, et al., Chem. Commun. 52 (2016) 12610–12613. doi: 10.1039/C6CC06627E
32. [32]
  D. Chen, T. Liu, J. Kang, et al., Adv. Mater. Interfaces 6 (2019) 1900706. doi: 10.1002/admi.201900706
33. [33]
  H. He, Y. Huang, Q. Zhang, et al., Cryst. Growth Des. 16 (2016) 2348–2356. doi: 10.1021/acs.cgd.6b00142
34. [34]
  L.Y. Wang, Y.M. Yu, F.B. Jiang, et al., New J. Chem. 44 (2020) 3930–3939. doi: 10.1039/c9nj06180k
35. [35]
  M. Davidson, N. Rashidi, M.K. Hossain, et al., Int. J. Mol. Sci. 24 (2023) 2737. doi: 10.3390/ijms24032737
36. [36]
  F. Racher, T.L. Petrick, D.E. Braun, Cryst. Growth Des. 23 (2023) 4638–4654. doi: 10.1021/acs.cgd.3c00387
37. [37]
  J. Makadia, C.C. Seaton, M. Li, Cryst. Growth Des. 23 (2023) 3480–3495. doi: 10.1021/acs.cgd.3c00030
38. [38]
  Y. Deng, S. Liu, Y. Jiang, et al., Pharmaceutics 15 (2023) 2174. doi: 10.3390/pharmaceutics15092174
39. [39]
  D. Musumeci, C.A. Hunter, R. Prohens, et al., Chem. Sci. 2 (2011) 883–890. doi: 10.1039/c0sc00555j
40. [40]
  H. Yu, B. Zhang, M. Liu, et al., Chin. Chem. Lett. 35 (2024) 109032. doi: 10.1016/j.cclet.2023.109032
41. [41]
  A.O. Surov, A.G. Ramazanova, A.P. Voronin, et al., Pharmaceutics 15 (2023) 836. doi: 10.3390/pharmaceutics15030836
42. [42]
  D. Yang, J. Cao, T. Heng, et al., Cryst. Growth Des. 21 (2021) 2292–2300. doi: 10.1021/acs.cgd.0c01706
43. [43]
  M. Borovina, I. Kodrin, M. Đaković, Cryst. Growth Des. 19 (2019) 1985–1995. doi: 10.1021/acs.cgd.8b01930
44. [44]
  B. Sandhu, S.A. Savage, H. Park, et al., Cryst. Growth Des. 22 (2022) 4105–4114. doi: 10.1021/acs.cgd.1c01486
1. [1]
  Hongmei Yu , Baoxi Zhang , Meiju Liu , Cheng Xing , Guorong He , Li Zhang , Ningbo Gong , Yang Lu , Guanhua Du . Theoretical and experimental cocrystal screening of temozolomide with a series of phenolic acids, promising cocrystal coformers. Chinese Chemical Letters, 2024, 35(5): 109032-. doi: 10.1016/j.cclet.2023.109032
2. [2]
  Zhiwei Chen , Heyun Sheng , Xue Li , Menghan Chen , Xin Li , Qiuling Song . Efficient capture of difluorocarbene by pyridinium 1,4-zwitterionic thiolates: A concise synthesis of difluoromethylene-containing 1,4-thiazine derivatives. Chinese Chemical Letters, 2024, 35(4): 108937-. doi: 10.1016/j.cclet.2023.108937
3. [3]
  Jing Guo , Zhi-Guo Lu , Rui-Chen Zhao , Bao-Ku Li , Xin Zhang . Nucleic acid therapy for metabolic-related diseases. Chinese Chemical Letters, 2025, 36(3): 109875-. doi: 10.1016/j.cclet.2024.109875
4. [4]
  Xiying Wu , Anze Liu , Yuzhong Yan , Ying Lu , Huan Wang . Folic acid ameliorates the immunogenicity of PEGylated liposomes. Chinese Chemical Letters, 2025, 36(6): 110285-. doi: 10.1016/j.cclet.2024.110285
5. [5]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
6. [6]
  Huipeng Zhao , Xiaoqiang Du . Polyoxometalates as the redox anolyte for efficient conversion of biomass to formic acid. Chinese Journal of Structural Chemistry, 2024, 43(2): 100246-100246. doi: 10.1016/j.cjsc.2024.100246
7. [7]
  Dan-Ying Xing , Xiao-Dan Zhao , Chuan-Shu He , Bo Lai . Kinetic study and DFT calculation on the tetracycline abatement by peracetic acid. Chinese Chemical Letters, 2024, 35(9): 109436-. doi: 10.1016/j.cclet.2023.109436
8. [8]
  Lihang Wang , Mary Li Javier , Chunshan Luo , Tingsheng Lu , Shudan Yao , Bing Qiu , Yun Wang , Yunfeng Lin . Research advances of tetrahedral framework nucleic acid-based systems in biomedicine. Chinese Chemical Letters, 2024, 35(11): 109591-. doi: 10.1016/j.cclet.2024.109591
9. [9]
  Zhifeng CAI , Ying WU , Yanan LI , Guiyu MENG , Tianyu MIAO , Yihao ZHANG . Effective detection of malachite green by folic acid stabilized silver nanoclusters. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 983-993. doi: 10.11862/CJIC.20240394
10. [10]
  Li Fu , Ziye Su , Shuyang Wu , Yanfen Cheng , Chuan Hu , Jinming Zhang . Redox-responsive hyaluronic acid-celastrol prodrug micelles with glycyrrhetinic acid co-delivery for tumor combination therapy. Chinese Chemical Letters, 2025, 36(5): 110227-. doi: 10.1016/j.cclet.2024.110227
11. [11]
  Hanqing Zhang , Xiaoxia Wang , Chen Chen , Xianfeng Yang , Chungli Dong , Yucheng Huang , Xiaoliang Zhao , Dongjiang Yang . Selective CO2-to-formic acid electrochemical conversion by modulating electronic environment of copper phthalocyanine with defective graphene. Chinese Journal of Structural Chemistry, 2023, 42(10): 100089-100089. doi: 10.1016/j.cjsc.2023.100089
12. [12]
  Linshan Peng , Qihang Peng , Tianxiang Jin , Zhirong Liu , Yong Qian . Highly efficient capture of thorium ion by citric acid-modified chitosan gels from aqueous solution. Chinese Chemical Letters, 2024, 35(5): 108891-. doi: 10.1016/j.cclet.2023.108891
13. [13]
  Yingying Yan , Wanhe Jia , Rui Cai , Chun Liu . An AIPE-active fluorinated cationic Pt(Ⅱ) complex for efficient detection of picric acid in aqueous media. Chinese Chemical Letters, 2024, 35(5): 108819-. doi: 10.1016/j.cclet.2023.108819
14. [14]
  Fengyun Li , Zerong Pei , Shuting Chen , Gen li , Mengyang Liu , Liqin Ding , Jingbo Liu , Feng Qiu . Multifunctional nano-herb based on tumor microenvironment for enhanced tumor therapy of gambogic acid. Chinese Chemical Letters, 2024, 35(5): 108752-. doi: 10.1016/j.cclet.2023.108752
15. [15]
  Zhen Liu , Zhi-Yuan Ren , Chen Yang , Xiangyi Shao , Li Chen , Xin Li . Asymmetric alkenylation reaction of benzoxazinones with diarylethylenes catalyzed by B(C₆F₅)₃/chiral phosphoric acid. Chinese Chemical Letters, 2024, 35(5): 108939-. doi: 10.1016/j.cclet.2023.108939
16. [16]
  Peizhe Li , Qiaoling Liu , Mengyu Pei , Yuci Gan , Yan Gong , Chuchen Gong , Pei Wang , Mingsong Wang , Xiansong Wang , Da-Peng Yang , Bo Liang , Guangyu Ji . Chlorogenic acid supported strontium polyphenol networks ensemble microneedle patch to promote diabetic wound healing. Chinese Chemical Letters, 2024, 35(8): 109457-. doi: 10.1016/j.cclet.2023.109457
17. [17]
  Yuanjiao Liu , Xiaoyang Zhao , Songyao Zhang , Yi Wang , Yutuo Zheng , Xinrui Miao , Wenli Deng . Site-selection and recognition of aromatic carboxylic acid in response to coronene and pyridine derivative. Chinese Chemical Letters, 2024, 35(8): 109404-. doi: 10.1016/j.cclet.2023.109404
18. [18]
  Shiyu Pan , Bo Cao , Deling Yuan , Tifeng Jiao , Qingrui Zhang , Shoufeng Tang . Complexes of cupric ion and tartaric acid enhanced calcium peroxide Fenton-like reaction for metronidazole degradation. Chinese Chemical Letters, 2024, 35(7): 109185-. doi: 10.1016/j.cclet.2023.109185
19. [19]
  Xubin Qian , Lei Xu , Xu Ge , Zhun Liu , Cheng Fang , Jianbing Wang , Junfeng Niu . Can perfluorooctanoic acid be effectively degraded using β-PbO₂ reactive electrochemical membrane?. Chinese Chemical Letters, 2024, 35(7): 109218-. doi: 10.1016/j.cclet.2023.109218
20. [20]
  Xinyue Lan , Junguang Liang , Churan Wen , Xiaolong Quan , Huimin Lin , Qinqin Xu , Peixian Chen , Guangyu Yao , Dan Zhou , Meng Yu . Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy. Chinese Chemical Letters, 2024, 35(4): 108616-. doi: 10.1016/j.cclet.2023.108616

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(10)
HTML views(1)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142