Generate QR code
Open Access
Subscription Access
Spectroscopic, Computational, and Crystallographic Study of Bioactive Hydroxypyrrolidin-2-One Derivatives
Abstract
Five variants of hydroxypyrrolidine-2-one have been synthesized through a solvent-free one-pot reaction employing n-propylamine, isopropylamine, and ethylenediamine with a 2(3H)-furanone derivative. The reaction products demonstrated exceptionally efficient yield and eco-friendliness. Spectroscopic analysis was applied to fully characterize the samples, complementing single-crystal X-ray diffraction analysis and computational outcomes. The single-crystal diffraction of compound 1 confirmed its crystallization in a monoclinic system. The structure demonstrates a significant density of O–H…O interactions between molecules, which is consistent with the findings of the Hirshfeld investigation. The density functional theory (DFT) results and the observed crystalline structure are compared. A notable correlation was identified between the observed and theoretical geometric values. For bioactivity to occur, the most electrophilic site must be near the hydroxyl group linked to the heterocyclic ring, as indicated by the molecule’s electrostatic potential. The frontier molecular orbitals were examined to determine the energy disparity between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), indicating significant molecular stability. At a dosage of 3.4 µg/mL, compound 1 exhibited potent anticancer efficacy against breast and colon tumors in the HCT-116 and MCF-7 cell lines, respectively. Moreover, compound 5 exhibited substantial antibacterial efficacy.
About the Authors
Mamoun S. M. Abd El-Kareem
Molecular and atomic physics unit., Experimental Nuclear Physics Dept., Nuclear Research Centre
Egypt
Egypt
Egyptian Atomic Energy Authority, Cairo
Ahmed F. Mabied
X-ray Crystallography Lab., Solid State Physics Department, National Research Centre
Egypt
Egypt
Dokki, Giza
Eman M. Azmy
Department of Chemistry, Faculty of Women for Arts, Science, and Education, Ain Shams University
Egypt
Egypt
Asmaa Fahmy Street, Heliopolis, Cairo
Boshra M. Awad
Department of Chemistry, Faculty of Women for Arts, Science, and Education, Ain Shams University
Egypt
Egypt
Asmaa Fahmy Street, Heliopolis, Cairo
References
1. V. O. Koz’minykh, N. M. Igidov, S. S. Zykova, V. É. Kolla, N. S. Shuklina, T. F. Odegova. Pharm. Chem. J., 36, 188–191 (2002), https://doi.org/10.1023/A:1019832621371.
2. Y. Geng, X. Wang, L. Yang, H. Sun, Y. Wang, Y. Zhao, R. She, M.-X. Wang, D.-X. Wang. PLoS One, 10, 1–15 (2015), https://doi.org/10.1371/journal.pone.0128928.
3. K. Ma, P. Wang, W. Fu, X. Wan, L. Zhou, Y. Chu, D. Ye. Bioorg. Med. Chem. Lett., 21, 6724–6727 (2011), https://doi.org/10.1016/J.BMCL.2011.09.054.
4. V. L. Gein, M. N. Armisheva, N. A. Rassudikhina, M. I. Vakhrin, E. V. Voronina. Pharm. Chem. J., 45, 162–164 (2011), https://doi.org/10.1007/s11094-011-0584-0.
5. V. L. Gein, V. A. Mihalev, N. N. Kasimova, E. V. Voronina, M. I. Vakhrin, E. B. Babushkina. Pharm. Chem. J., 41, 208–210 (2007), https://doi.org/10.1007/s11094-007-0047-9.
6. V. L. Gein, V. V. Yushkov, N. N. Kasimova, N. S. Shuklina, M. Yu. Vasil’eva, M. V. Gubanova. Pharm. Chem. J., 39, 484–487 (2005), https://doi.org/10.1007/s11094-006-0006-x.
7. M. S. F. Franco, G. A. Casagrande, C. Raminelli, S. Moura, M. Rossatto, F. H. Quina, C. M. P. Pereira, A. F. C. Flores, L. Pizzuti. Synth. Commun., 45, 692–701 (2015), https://doi.org/10.1080/00397911.2014.978504.
8. M. Anada, S. Hashimoto. Tetrahedron. Lett., 39, 79–82 (1998), https://doi.org/10.1016/S00404039(97)10493-2.
9. D.-R. Choi, K.-Y. Lee, Y.-S. Chung, J.-E. Joo, Y.-H. Kim, C.-Y. Oh, Y.-S. Lee, W.-H. Ham. Arch. Pharm. Res., 28, 151–158 (2005), http://www.ncbi.nlm.nih.gov/pubmed/15789742 (accessed June 19, 2018).
10. L. E. Burgess, A. I. Meyers. J. Org. Chem., 57, 1656–1662 (1992), https://doi.org/10.1021/jo00032a012.
11. L. E. Overman, T. P. Remarchuk. J. Am. Chem. Soc., 124, 12–13 (2002), https://doi.org/10.1021/ja017198n.
12. V. Singh, R. Saxena, S. Batra. J. Org. Chem., 70, 353–356 (2005), https://doi.org/10.1021/jo048411b.
13. R. Sarkar, C. Mukhopadhyay. Tetrahedron Lett., 54, 3706–3711 (2013), https://doi.org/10.1016/J.TETLET.2013.05.017.
14. J. Sun, Q. Wu, E.-Y. Xia, C.-G. Yan. Eur. J. Org. Chem., 2981–2986 (2011), https://doi.org/10.1002/ejoc.201100008.
15. Q. Zhu, H. Jiang, J. Li, S. Liu, C. Xia, M. Zhang. J. Comb. Chem., 11, 685–696 (2009), https://doi.org/10.1021/cc900046f.
16. B. M. Awad, H. A. Saad, E. M. Nassar, E. M. Azmy. J. Am. Sci., 9, 566–577 (2013), https://doi.org/10.7537/marsjas090613.71.
17. P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J. T. Warren, H. Bokesch, S. Kenney, M. R. Boyd. J. Natl. Cancer. Inst., 82, 1107–1112 (1990), http://www.ncbi.nlm.nih.gov/pubmed/2359136 (accessed June 19, 2018).
18. B. F. Abdel-Wahab, M. H. Sharaf, J. C. Fettinger, A. A. Farahat, A. F. Mabied. Chem. Select, 9, e202402829 (2024), https://doi.org/10.1002/SLCT.202402829.
19. H. D. Flack, G. Bernardinelli. Use of X-ray crystallography to determine absolute configuration, Chirality, 20, 681–690 (2008), https://doi.org/10.1002/chir.20473.
20. M. A. Spackman, D. Jayatilaka. Cryst. Eng. Comm., 11, 19–32 (2009), https://doi.org/10.1039/B818330A.1
21. A. F. Mabied, A. H. Moustafa, A. A. Abdelhamid, T. M. Tiama, A. A. Amer. Sci. Rep., 13, 19510 (2023), https://doi.org/10.1038/s41598-023-45533-1.
22. A. F. Mabied, A. H. Moustafa, A. A. Abdelhamid, T. M. Tiama, A. A. Amer. Chem. Select., 9, e202304470 (2024), https://doi.org/10.1002/slct.202304470.
23. E. A. Ahmed, K. M. Mohamed, S. A. Thabet, A. H. Moustafa, A. F. Mabied, A. Khodairy. Synth. Commun., 53, 1020–1029 (2023), https://doi.org/10.1080/00397911.2023.2207127.
24. A. H. Moustafa, W. W. Ahmed, A. Khodairy, A. F. Mabied, A. Moustafa, M. F. El-Sayed. J. Mol. Struct., 1230, 129888 (2021), https://doi.org/10.1016/j.molstruc.2021.129888.
25. A. F. Mabied, E. M. Shalaby, H. A. Zayed, I. S. A. Farag. J. Crystallogr., 1–6 (2014), http://www.hindawi.com/journals/jcrys/2014/179671/.
26. E. M. Azmy, B. M. Awad, H. A. Hefni, H. A. Saad, A. M. Eltoukhya, A. F. Mabied, M. S. M. A. ElKareem, N. Demitri. J. Appl. Spectrosc., 88, 414–423 (2021), https://doi.org/10.1007/s10812-021-01189-1.
27. E. Azmy, B. Awad, H. Hefni, H. Saad, A. Eltoukhy, A. Mabied. J. Sci. Res. Sci., 35, 1–16 (2018), https://doi.org/10.21608/jsrs.2018.15776.
28. A. Lausi, M. Polentarutti, S. Onesti, J. R. Plaisier, E. Busetto, G. Bais, L. Barba, A. Cassetta, G. Campi, D. Lamba, A. Pifferi, S. C. Mande, D. D. Sarma, S. M. Sharma, G. Paolucci. Eur. Phys. J. Plus, 130, 43 (2015), https://doi.org/10.1140/epjp/i2015-15043-3.
29. W. Kabsch. Acta Crystallogr. D: Biol. Crystallogr., 66, 125–132 (2010), https://doi.org/10.1107/S0907444909047337.
30. G. M. Sheldrick. Acta Crystallogr. A: Found Adv., 71, 3–8 (2015), https://doi.org/10.1107/S2053273314026370.
31. A. L. Spek. Acta Crystallogr. D: Biol. Crystallogr., 65, 148–155 (2009), https://doi.org/10.1107/S090744490804362X.
32. L. J. Farrugia. J. Appl. Crystallogr., 45, 849–854 (2012), https://doi.org/10.1107/S0021889812029111.
33. F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen, R. Taylor. J. Chem. Soc., Perkin Transactions, 2 (1987) S1, https://doi.org/10.1039/p298700000s1.
34. P. R. Spackman, M. J. Turner, J. J. McKinnon, S. K. Wolff, D. J. Grimwood, D. Jayatilaka, M. A. Spackman. J. Appl. Crystall., 54, 1006–1011 (2021), https://doi.org/10.1107/S1600576721002910.
35. J. Foresman, A. Frisch. Exploring Chemistry with Electronic Structure Methods, Gaussian Inc, Pittsburgh, PA (1996).
36. M. J. Frisch, G. W. Trucks, H. B. Schlegel, et al. Gaussian09, Revision, Gaussian Inc., Wallingford CT (2009).
37. A. Frisch, A. B. Nielson, A. J. Holder. Gauss View User Manual, Gaussian Inc., Pittsburgh, P. A. (2005).
38. B. D. Joshi, R. Mishra, P. Tandon, A. C. Oliveira, A. P. Ayala. J. Mol. Struct., 1058, 31–40 (2014), https://doi.org/10.1016/j.molstruc.2013.10.062.
39. C. Muñoz-Caro, A. Niño, M. L. Senent, J. M. Leal, S. Ibeas. J. Org. Chem., 65, No. 2, 405–410 (2000), https://doi.org/10.1021/jo991251x.
40. J. Yu, N. Q. Su, W. Yang. JACS Au, 2, No. 6, 1383–1394 (2022), https://doi.org/10.1021/JACSAU.2C00085.
Review
For citations:
Abd El-Kareem M., Mabied A., Azmy E., Awad B. Spectroscopic, Computational, and Crystallographic Study of Bioactive Hydroxypyrrolidin-2-One Derivatives. Zhurnal Prikladnoii Spektroskopii. 2025;92(5):706.
Views:
27
Email this article 