Abstract
Fluorinated chalcones are organic compounds with diverse biological activities and are of interest for drug development due to their improved properties, such as lipophilicity, bioavailability, and metabolic stability. Therefore, the correlation between structure and properties is fundamental to discover the potential use on pharmaceutical and technological applications. In this sense, we synthesized and characterized a novel fluorinated chalcone (E)-1-(4-fluorophenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (FCH), and compared its supramolecular arrangement and topological analysis with a chalcone (E)-1-(4-hydroxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (HCH). The molecular electrostatic potential, QTAIM, and frontier molecular orbitals of both chalcones were investigated using the M06-2X/6-311++G(d,p) level of theory. Our findings show that the FCH exhibits a herringbone packing with intermolecular interactions of C–H⋯F and C–H⋯π, while the HCH assumes a staircase packing coordinated by O–H⋯O and π⋯π intermolecular interactions. Furthermore, the electrostatic potential analysis shows that FCH is susceptible to electrophilic attack, while HCH is susceptible to nucleophilic attack. Finally, the structural basis analysis for both chalcones indicated that FCH has a higher lipophilicity than HCH due to the stronger hydrogen bond of HCH with water.
Funding source: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Award Identifier / Grant number: Unassigned
Funding source: Fundação de Amparo à Pesquisa do Estado de Goiás
Award Identifier / Grant number: Unassigned
Funding source: Fundação Nacional de Desenvolvimento do Ensino Superior Particular
Award Identifier / Grant number: Unassigned
Funding source: Conselho Nacional de Desenvolvimento Científico e Tecnológico
Award Identifier / Grant number: Unassigned
Acknowledgments
The authors are grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Fundação de Amparo à Pesquisa do Estado de Goiás, Fundação Nacional de Desenvolvimento do Ensino Superior Particular and Conselho Nacional de Desenvolvimento Científico e Tecnológico for financial support. Also, the authors are grateful to the High-Performance Computing Center of the Universidade Estadual de Goiás (UEG) and the Centro de Análises, Inovação e Tecnologia da UEG (CAiTec).
-
Author contributions: Lóide O. Sallum: Conceptualization, Writing – original draft. Lorraine F. Silva: Investigation, Data curation, Software, Writing – review & editing. Jaqueline E. Queiroz: Writing – original draft, Investigation, Data curation, and review. Vitor S. Duarte: Formal analysis, Writing – review & editing. Wesley F. Vaz: Visualization, Writing – review & editing. Marcelo Z. Hernandes: Conceptualization, Formal analysis, Writing – review & editing. Gilberto L.B. Aquino: Visualization, Writing – review & editing. Ademir J. Camargo: Formal analysis, Writing – review & editing. Hamilton B. Napolitano: Project administration, Conceptualization, Supervision, Investigation, Writing – review & editing, Resources.
-
Research funding: None declared.
-
Conflict of interest statement: The authors declare there are no conflicts of interest.
References
1. CAMPOS MGI, CUNHA AP Flavonoides. In: Farmacognosia e Fitoquímica, 3. Aufl. Fundação Calouste Gulbenkian: Lisboa, 2010; S 238–289.book-chapterSearch in Google Scholar
2. ZUANAZZI JAS, In: SIMÕES CMO Flavonoides. In: Farmacognosia: da planta ao medicamento, 3. Aufl. Editora da UFSC, Florianópolis, 2001; S 499–526.Search in Google Scholar
3. Yadav, V. R., Prasad, S., Sung, B., Aggarwal, B. B. The role of chalcones in suppression of NF-κB-Mediated inflammation and cancer. Int. Immunopharmacol. 2011, 11, 295–309. https://doi.org/10.1016/J.INTIMP.2010.12.006.Search in Google Scholar PubMed PubMed Central
4. CHOPRA PKPG CHALCONES: a brief review. Int. J. Res. Eng. Appl. Sci. 2016, 6, 173–185.Search in Google Scholar
5. Bandgar, B. P., Patil, S. A., Gacche, R. N., Korbad, B. L., Hote, B. S., Kinkar, S. N., Jalde, S. S. Synthesis and biological evaluation of nitrogen-containing chalcones as possible anti-inflammatory and antioxidant agents. Bioorg. Med. Chem. Lett. 2010, 20, 730–733. https://doi.org/10.1016/J.BMCL.2009.11.068.Search in Google Scholar PubMed
6. Quideau, S. Flavonoids. Chemistry, Biochemistry and Applications. In Angewandte Chemie International Edition; CRC Press/Taylor & Francis: Boca Raton, 2006.Search in Google Scholar
7. Padhye, S., Ahmad, A., Oswal, N., Dandawate, P., Rub, R. A., Deshpande, J., Swamy, K. V., Sarkar, F. H. Fluorinated 2′-hydroxychalcones as garcinol analogs with enhanced antioxidant and anticancer activities. Bioorg. Med. Chem. Lett. 2010, 20, 5818–5821. https://doi.org/10.1016/j.bmcl.2010.07.128.Search in Google Scholar PubMed
8. Yadav, P., Lal, K., Kumar, L., Paul, A. K., Kumar, R. Synthesis, crystal structure and antimicrobial potential of some fluorinated chalcone-1,2,3-triazole conjugates. Eur. J. Med. Chem. 2018, 155, 263–274. https://doi.org/10.1016/j.ejmech.2018.05.055.Search in Google Scholar PubMed
9. Burmaoglu, S., Algul, O., Anil, D. A., Gobek, A., Duran, G. G., Ersan, R. H., Duran, N. Synthesis and anti-proliferative activity of fluoro-substituted chalcones. Bioorg. Med. Chem. Lett. 2016, 26, 3172–3176. https://doi.org/10.1016/J.BMCL.2016.04.096.Search in Google Scholar
10. Hasan, S. A., Elias, A. N., Jwaied, A. H., Khuodaer, A. H., Hussain, A. R., Abdulrahman, S. Synthesis of new fluorinated chalcone derivative with anti-inflammatory activity. Int. J. Pharm. Pharm. Sci. 2012, 4, 430–434.Search in Google Scholar
11. Mathew, B., Adeniyi, A. A., Joy, M., Mathew, G. E., Singh-Pillay, A., Sudarsanakumar, C., Soliman, M. E., Suresh, J. Anti-oxidant behavior of functionalized chalcone-a combined quantum chemical and crystallographic structural investigation. J. Mol. Struct. 2017, 1146, 301–308. https://doi.org/10.1016/j.molstruc.2017.05.100.Search in Google Scholar
12. Ojima, I. Fluorine in Medicinal Chemistry and Chemical Biology; Blackwell Publishing, Ltd.: Hoboken, New Jersey, 2009.10.1002/9781444312096Search in Google Scholar
13. Zaldini Hernandes, M., Melo Cavalcanti, S. T., Rodrigo Moreira, D. M., de Azevedo Junior, W., Leite, A. C. Halogen atoms in the modern medicinal chemistry: hints for the drug design. Curr. Drug Targets 2010, 11, 303–314; https://doi.org/10.2174/138945010790711996.Search in Google Scholar PubMed
14. Sheldrick, G. M. SHELXT – integrated space-group and crystal-structure determination. Acta Crystallogr. A 2015, 71, 3–8. https://doi.org/10.1107/S2053273314026370.Search in Google Scholar PubMed PubMed Central
15. Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Crystallogr. C Struct. Chem. 2015, 71, 3–8. https://doi.org/10.1107/S2053229614024218.Search in Google Scholar PubMed PubMed Central
16. Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K., Puschmann, H. OLEX2 : a complete structure solution, refinement and analysis program. J. Appl. Crystallogr. 2009, 42, 339–341. https://doi.org/10.1107/S0021889808042726.Search in Google Scholar
17. Wolff, S. K., Grimwood, D. J., McKinnon, J. J., Turner, M. J., Jayatilaka, D., Spackman, M. A. Crystal Explorer (version 3.1); University of Western Australia: Australia, 2012.Search in Google Scholar
18. Groom, C. R., Bruno, I. J., Lightfoot, M. P., Ward, S. C. The Cambridge structural database. Acta Crystallogr. B Struct. Sci. Crystallogr. Eng. Mater. 2016, 72, 171–179. https://doi.org/10.1107/S2052520616003954.Search in Google Scholar PubMed PubMed Central
19. Lindon, J. C., Tranter, G. E., Koppenaal, D. Encyclopedia of Spectroscopy and Spectrometry, 3rd ed.; Elsevier Science: Amsterdam, 2017.Search in Google Scholar
20. Hachani, A., Dridi, I., Elleuch, S., Roisnel, T., Kefi, R. Crystal structure, spectroscopic and biological study of a new inorganic–organic hybrid compound [Cd4Cl12(H2O)2]n (C10N4H28)n. Inorg. Chem. Commun. 2019, 100, 134–143. https://doi.org/10.1016/j.inoche.2018.12.006.Search in Google Scholar
21. Spackman, M. A., Jayatilaka, D. Hirshfeld surface analysis. CrystEngComm 2009, 11, 19–32. https://doi.org/10.1039/b818330a.Search in Google Scholar
22. Spackman, P. R., Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Jayatilaka, D., Spackman, M. A. CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals. J. Appl. Crystallogr. 2021, 54, 1006–1011. https://doi.org/10.1107/S1600576721002910.Search in Google Scholar PubMed PubMed Central
23. Frisch, M. J., Trucks, G. W., Schlegel, H. B., et al.. Gaussian 09, Revision A.02; Gaussian Inc.: Wallingford CT, 2009; pp. 201.Search in Google Scholar
24. Hohenstein, E. G., Chill, S. T., Sherrill, C. D. Assessment of the performance of the M05#2X and M06#2X for noncovalent interactions in biomolecules. J. Chem. Theory Comput. 2008, 4, 1996–2000. https://doi.org/10.1021/ct800308k.Search in Google Scholar PubMed
25. Sousa, S. F., Fernandes, P. A., Ramos, M. J. General performance of density functionals. J. Phys. Chem. A 2007, 111, 10439–10452. https://doi.org/10.1021/jp0734474.Search in Google Scholar PubMed
26. Wiberg, K. B., Box, P. O., Haven, N. Basis set effects on calculated geometries : 6-311++ G ** vs. aug-cc-pVDZ. J. Comput. Chem. 2004, 25, 1342–1346. https://doi.org/10.1002/jcc.20058.Search in Google Scholar PubMed
27. Zhao, Y., Truhlar, D. G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other function. Theor. Chem. Acc. 2008, 120, 215–241. https://doi.org/10.1007/s00214-007-0310-x.Search in Google Scholar
28. Grant, G. H., Richards, W. G., William, G. Computational Chemistry; Oxford University Press: Oxford, 1996.Search in Google Scholar
29. Pereira, D. H., Porta, F. A. La., Santiago, R. T., Garcia, D. R., Ramalho, T. C. New perspectives on the role of frontier molecular orbitals in the study of chemical reactivity: a review. Revista Virtual de Química 2016, 8, 425–453. https://doi.org/10.5935/1984-6835.20160032.Search in Google Scholar
30. Omar, S., Mohd, S., Ajmal Khan, M., Ahmad, Z., AlFaify, S. A comprehensive study on molecular geometry, optical, HOMO-LUMO, and nonlinear properties of 1,3-diphenyl-2-propen-1-ones chalcone and its derivatives for optoelectronic applications: a computational approach. Optik 2020, 204, 164172. https://doi.org/10.1016/j.ijleo.2020.164172.Search in Google Scholar
31. Zhang, G., Musgrave, C. B. Comparison of DFT methods for molecular orbital eigenvalue calculations. J. Phy. Chem. A 2007, 111, 1554–1561; https://doi.org/10.1021/jp061633o.Search in Google Scholar PubMed
32. Sjoberg, P., Politzer, P. Use of the electrostatic potential at the molecular surface. J. Phy. Chem. 1990, 94, 3959–3961; https://doi.org/10.1021/j100373a017.Search in Google Scholar
33. Bader, R. F. W. Atoms in molecules. Acc. Chem. Res. 1985, 18, 9–15. https://doi.org/10.1021/ar00109a003.Search in Google Scholar
34. Bader, R. F. W. The quantum mechanical basis of conceptual chemistry. Monatsh. Chem. 2005, 136, 819–854. https://doi.org/10.1007/s00706-005-0307-x.Search in Google Scholar
35. Bader, R. F. W. Atoms in molecules in external fields. J. Chem. Phys. 1989, 91, 6989. https://doi.org/10.1063/1.457315.Search in Google Scholar
36. Lu, T., Chen, F. Multiwfn: a multifunctional wavefunction analyzer. J. Comput. Chem. 2012, 33, 580–592. https://doi.org/10.1002/jcc.22885.Search in Google Scholar PubMed
37. Daina, A., Michielin, O., Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017, 7, 1–13. https://doi.org/10.1038/srep42717.Search in Google Scholar PubMed PubMed Central
38. Macrae, C. F., Bruno, I. J., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J., Wood, P. A. Mercury CSD 2.0 – new features for the visualization and investigation of crystal structures. J. Appl. Crystallogr. 2008, 41, 466–470; https://doi.org/10.1107/S0021889807067908.Search in Google Scholar
39. Maragatham, G., Selvarani, S., Rajakumar, P., Lakshmi, S. Structure determination and quantum chemical analysis of chalcone derivatives. J. Mol. Struct. 2019, 1179, 568–575. https://doi.org/10.1016/j.molstruc.2018.11.048.Search in Google Scholar
40. Bernstein, J., Davis, R. E., Shimoni, L., Chang, N.-L. Patterns in hydrogen bonding: functionality and graph set analysis in crystals. Angew. Chem. Int. Ed. Engl. 1995, 34, 1555–1573. https://doi.org/10.1002/anie.199515551.Search in Google Scholar
41. Lipinski, C. A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today Technol. 2004, 1, 337–341. https://doi.org/10.1016/j.ddtec.2004.11.007.Search in Google Scholar PubMed
42. Politzer, P., Laurence, P. R., Jayasuriya, K. Molecular electrostatic potentials: an effective tool for the elucidation of biochemical phenomena. Environ. Health Perspect. 1985, 61, 191–202. https://doi.org/10.1289/ehp.8561191.Search in Google Scholar PubMed PubMed Central
43. Murray, J. S., Politzer, P. The Electrostatic Potential: An Overview. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2011, 1, 153–163. https://doi.org/10.1002/wcms.19.Search in Google Scholar
44. Gatti, C., Saunders, V. R., Roetti, C. Crystal field effects on the topological properties of the electron density in molecular crystals: the case of urea. J. Chem. Phys. 1994, 101, 10686–10696. https://doi.org/10.1063/1.467882.Search in Google Scholar
45. TYu, N., Bulavin, L. A., Hovorun, D. M. Bridging QTAIM with vibrational spectroscopy: the energy of intramolecular hydrogen bonds in DNA-related biomolecules. Phys. Chem. Chem. Phys. 2012, 14, 7441. https://doi.org/10.1039/c2cp40176b.Search in Google Scholar PubMed
46. Ośmiałowski, B. Substituent effects in hydrogen bonding: DFT and QTAIM studies on acids and carboxylates complexes with formamide. J. Mol. Model. 2014, 20, 2356. https://doi.org/10.1007/s00894-014-2356-8.Search in Google Scholar PubMed PubMed Central
47. Vener, M. V., Manaev, A. V., Egorova, A. N., Tsirelson, V. G. QTAIM study of strong H-bonds with the O–H⋯A fragment (A = O, N) in three-dimensional periodical crystals. J. Phys. Chem. A 2007, 111, 1155–1162. https://doi.org/10.1021/jp067057d.Search in Google Scholar PubMed
48. Arkhipov, D. E., Lyubeshkin, A. V., Volodin, A. D., Korlyukov, A. A. Molecular structures polymorphism the role of F…F interactions in crystal packing of fluorinated tosylates. Crystals 2019, 9, 242. https://doi.org/10.3390/cryst9050242.Search in Google Scholar
49. Bagheri, S., Masoodi, H. R., Yousofvand, A. Exploring the role of substituents on cooperativity between N⋯HF and CH⋯F hydrogen bonds in ternary systems involving aromatic azine: substituted complexes of s-triazine:HF:s-triazine as a working model. Comput. Theor. Chem. 2016, 1092, 12–18. https://doi.org/10.1016/j.comptc.2016.07.002.Search in Google Scholar
50. Li, F., Zheng, Z., Xia, S., Yu, L. Synthesis, co-crystal structure, and DFT calculations of a multicomponent co-crystal constructed from 1H-benzotriazole and tetrafluoroterephthalic acid. J. Mol. Struct. 2020, 1219, 128480. https://doi.org/10.1016/j.molstruc.2020.128480.Search in Google Scholar
51. Mondal, S., Biswas, B., Sarkar, S., Singh, P. C. A combined molecular dynamics simulation, atoms in molecule analysis and IR study on the biologically important bulk fluorinated ethanols to understand the role of weak interactions in their cluster formation and hydrogen bond network. J. Mol. Liq. 2017, 240, 708–716. https://doi.org/10.1016/j.molliq.2017.05.098.Search in Google Scholar
52. Popelier, P. L. A. Characterization of a dihydrogen bond on the basis of the electron density. J. Phys. Chem. A 1998, 102, 1873–1878; https://doi.org/10.1021/jp9805048.Search in Google Scholar
53. Carroll, M. T., Bader, R. F. W. An analysis of the hydrogen bond in BASE-HF complexes using the theory of atoms in molecules. Mol. Phys. 1988, 65, 695–722. https://doi.org/10.1080/00268978800101351.Search in Google Scholar
54. Bader, R. F. W. Atoms in Molecules: A Quantum Theory; Clarendon Press: Ontario, 1990.10.1093/oso/9780198551683.001.0001Search in Google Scholar
55. Rozas, I., Alkorta, I., Elguero, J. Behavior of ylides containing N, O, and C atoms as hydrogen bond acceptors. J. Am. Chem. Soc. 2000, 122, 11154–11161. https://doi.org/10.1021/ja0017864.Search in Google Scholar
56. Hilal, R., Aziz, S. G., Alyoubi, A. O., Elroby, S. Quantum topology of the charge density of chemical bonds. QTAIM analysis of the C-Br and O-Br bonds. J. Phys. Chem. A 2015, 111, 1872–1877; https://doi.org/10.1016/j.procs.2015.05.423.Search in Google Scholar
57. Koch, U., Popelier, P. L. A. Characterization of C–H–O hydrogen bonds on the basis of the charge density. J. Phys. Chem. 1995, 99, 9747–9754. https://doi.org/10.1021/j100024a016.Search in Google Scholar
58. Silva López, C., Nieto Faza, O., Cossió, F. P., York, D. M., de Lera, A. R. Ellipticity: a convenient tool to characterize electrocyclic reactions. Chem. Eur. J. 2005, 11, 1734–1738. https://doi.org/10.1002/chem.200401026.Search in Google Scholar PubMed
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/zkri-2022-0066).
© 2023 Walter de Gruyter GmbH, Berlin/Boston
