Abstract
A new Schiff base compound of N′-[(2,6-dichlorophenyl)methylidene]-2-{[3-(trifluoro-methyl)phenyl] amino}benzohydrazide was synthesized and characterized through various spectroscopic techniques, including infrared,1H NMR, 13C NMR spectroscopy and X-ray diffraction. Experimental results collected by XRD were compared with theoretical results obtained from Density functional theory method. Hirshfeld surface analysis was used to obtain three-dimension molecular surface and two-dimension fingerprint plots to illustrate the intermolecular bonding. Theoretical calculations provide valuable insights into both global and local chemical activity, as well as the properties of molecules and chemicals, including their nucleophilic and electrophilic nature. The DFT method at B3LYP/6-311++G(d,p) basis set was employed to study the optimized structure and geometric parameters, as well as to explore the frontier molecular orbitals, global reactive parameters, Mullikan population analaysis, Natural bond orbital and molecular electrostatic potential characteristics which cannot be obtained by experimental methods. Additionally, electrophilicity based charge transfer study was carried out with DNA bases to determine the direction of charge transfer. Finally, an investigation was carried out using molecular docking analysis to examine the binding energies of the title compound with PDB ID: 2QDJ protein target. The analysis yielded significant insights into the possible interactions, offering valuable findings in the process.
REFERENCES
G. Verma, A. Marella, M. Shaquiquzzaman, M. Akhtar, M. Ali, and M. Alam. A review exploring biological activities of hydrazones. J. Pharm. Bioallied Sci., 2014, 6(2), 69. https://doi.org/10.4103/0975-7406.129170
F. Tok, B. N. Sağlık, Y. Özkay, Z. A. Kaplancıklı, and B. Koçyiğit-Kaymakçıoğlu. N-substituted arylidene-3-(methylsulfonyl)-2-oxoimidazolidine-1-carbohydrazide as cholinesterase inhibitors: Design, synthesis, and molecular docking study. Chem. Biodivers., 2022, 19(8). https://doi.org/10.1002/cbdv.202200265
K. Akdağ, G. Ünal, F. Tok, F. Arıcıoğlu, H. Temel, and B. Kaymakcıoğlu-Koçyiğit. Synthesis and biological evaluation of some new hydrazone derivatives bearing pyrimidine ring as analgesic and anti-inflammatory agents. Acta Pol. Pharm. - Drug Res., 2018, 75(5), 1147-1159. https://doi.org/10.32383/appdr/86743
B. Kocyigit-Kaymakcioglu, S. S. Yazici, F. Tok, M. Dikmen, S. Engür, E. E. Oruc-Emre, and A. Iyidogan. Synthesis and anticancer activity of new hydrazide-hydrazones and their Pd(II) complexes. Lett. Drug Des. Discov., 2019, 16(5), 522-532. https://doi.org/10.2174/1570180815666180816124102
S. Şenkardeş, Ö. Erdoğan, Ö. Çevik, and Ş. G. Küçükgüzel. Synthesis and biological evaluation of novel aryloxyacetic acid hydrazide derivatives as anticancer agents. Synth. Commun., 2021, 51(17), 2634-2643. https://doi.org/10.1080/00397911.2021.1945105
A. E. Evren, D. Nuha, S. Dawbaa, B. N. Sağlık, and L. Yurttaş. Synthesis of novel thiazolyl hydrazone derivatives as potent dual monoamine oxidase-aromatase inhibitors. Eur. J. Med. Chem., 2022, 229, 114097. https://doi.org/10.1016/j.ejmech.2021.114097
D. Osmaniye, B. N. Sağlık, S. Levent, Y. Özkay, and Z. A. Kaplancıklı. Design, synthesis and biological evaluation of new N-acyl hydrazones with a methyl sulfonyl moiety as selective COX-2 inhibitors. Chem. Biodivers., 2021, 18(11). https://doi.org/10.1002/cbdv.202100521
I. Aprahamian. Hydrazone switches and things in between. Chem. Commun., 2017, 53(50), 6674-6684. https://doi.org/10.1039/c7cc02879b
L. A. Tatum, X. Su, and I. Aprahamian. Simple hydrazone building blocks for complicated functional materials. Acc. Chem. Res., 2014, 47(7), 2141-2149. https://doi.org/10.1021/ar500111f
W. Paulus, H. Ringsdorf, S. Diele, and G. Pelzl. Columnar phases from semi-discoid molecules. Phase induction via hydrogen bonding and charge transfer interactions. Liq. Cryst., 1991, 9(6), 807-819. https://doi.org/10.1080/02678299108055003
N. S. Al-Kadhi, F. S. Alamro, S. A. Popoola, S. M. Gomha, N. S. Bedowr, S. S. Al-Juhani, and H. A. Ahmed. Novel imidazole liquid crystals; experimental and computational approaches. Molecules, 2022, 27(14), 4607. https://doi.org/10.3390/molecules27144607
X. Su and I. Aprahamian. Hydrazone-based switches, metallo-assemblies and sensors. Chem. Soc. Rev., 2014, 43(6), 1963. https://doi.org/10.1039/c3cs60385g
M. E. Belowich and J. F. Stoddart. Dynamic imine chemistry. Chem. Soc. Rev., 2012, 41(6), 2003. https://doi.org/10.1039/c2cs15305j
F. R. Japp and F. Klingemann. Ueber Benzolazo- und Benzolhydrazofettsäuren. Ber. Dtsch. Chem. Ges., 1887, 20(2), 2942-2944. https://doi.org/10.1002/cber.188702002165
S. Wagaw, B. H. Yang, and S. L. Buchwald. A palladium-catalyzed strategy for the preparation of indoles: A novel entry into the fischer indole synthesis. J. Am. Chem. Soc., 1998, 120(26), 6621/6622. https://doi.org/10.1021/ja981045r
Ł. Popiołek. Hydrazide–hydrazones as potential antimicrobial agents: Overview of the literature since 2010. Med. Chem. Res., 2017, 26(2), 287-301. https://doi.org/10.1007/s00044-016-1756-y
S. Karakuş, A. Maryam, E. E. Oruç-Emre, and S. Türk. Synthesis, characterization, antituberculosis activity and computational studies on novel Schiff bases of 1,3,4-thiadiazole derivatives. J. Res. Pharm., 2020, 24(6), 793-800. https://doi.org/10.35333/jrp.2020.232
H. Cevher Koç, İ. Atlihan, P. M. Tiber, O. Orun, and Ş. G. Küçükgüzel. Synthesis and anticancer activity against prostate cancer of hydrazide-hydrazones derived from etodolac. J. Res. Pharm., 2022, 26(1), 1018-1029. https://doi.org/10.29228/jrp.97
G. Sheldrick. SHELXS-2014, program for crystal structure solution. Göttingen, Germany: University of Göttingen, 2014.
G. Sheldrick. SHELXL-2018/3 software package. Göttingen, Germany: University of Göttingen, 2018.
L. J. Farrugia. WinGX suite for small-molecule single-crystal crystallography. J. Appl. Crystallogr., 1999, 32(4), 837/838. https://doi.org/10.1107/s0021889899006020
L. J. Farrugia. WinGX and ORTEP for Windows: an update. J. Appl. Crystallogr., 2012, 45(4), 849-854. https://doi.org/10.1107/s0021889812029111
C. F. Macrae, I. Sovago, S. J. Cottrell, P. T. A. Galek, P. McCabe, E. Pidcock, M. Platings, G. P. Shields, J. S. Stevens, M. Towler, and P. A. Wood. Mercury 4.0: from visualization to analysis, design and prediction. J. Appl. Crystallogr., 2020, 53(1), 226-235. https://doi.org/10.1107/s1600576719014092
A. L. Spek. Single-crystal structure validation with the program PLATON. J. Appl. Crystallogr., 2003, 36(1), 7-13. https://doi.org/10.1107/s0021889802022112
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, and D. J. Fox. Gaussian09. Wallingford, CT, USA: Gaussian, Inc., 2009.
Z. Zahraee and H. Golchoubian. Solvatochromic, halochromic and thermochromic effects of copper(II) complexes containing N-tert-butyl 2-picolylamine, and halide ion; a computational study. J. Mol. Struct., 2023, 1285, 135483. https://doi.org/10.1016/j.molstruc.2023.135483
A. D. Becke. Density-functional thermochemistry. I. The effect of the exchange-only gradient correction. J. Chem. Phys., 1992, 96(3), 2155-2160. https://doi.org/10.1063/1.462066
M. E. Casida, C. Jamorski, K. C. Casida, and D. R. Salahub. Molecular excitation energies to high-lying bound states from time-dependent density-functional response theory: Characterization and correction of the time-dependent local density approximation ionization threshold. J. Chem. Phys., 1998, 108(11), 4439-4449. https://doi.org/10.1063/1.475855
M. F. Sanner. Python: a programming language for software integration and development. J. Mol. Graph. Model., 1999, 17(1), 57-61.
Visualizer DS, v.17.2.0.16349. San Diego, USA: Dassault Systemes Biovia, 2016.
L. A. Anthony, D. Rajaraman, G. Sundararajan, M. Suresh, P. Nethaji, R. Jaganathan, and K. Poomani. Synthesis, crystal structure, Hirshfeld surface analysis, DFT, molecular docking and molecular dynamic simulation studies of (E)-2,6-bis(4-chlorophenyl)-3-methyl-4-(2-(2,4,6-trichlorophenyl)hydrazono)piperidine derivatives. J. Mol. Struct., 2022, 1266, 133483. https://doi.org/10.1016/j.molstruc.2022.133483
S. Murugavel, C. Ravikumar, G. Jaabil, and P. Alagusundaram. Synthesis, crystal structure analysis, spectral investigations (NMR, FT-IR, UV), DFT calculations, ADMET studies, molecular docking and anticancer activity of 2-(1-benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(2-chlorophenyl)-6-methoxypyridine - A novel potent human topoisomerase IIα inhibitor. J. Mol. Struct., 2019, 1176, 729-742. https://doi.org/10.1016/j.molstruc.2018.09.010
M. Ashfaq, G. Bogdanov, A. Ali, M. N. Tahir, and S. Abdullah. Pyrimethamine-based novel co-crystal salt: Synthesis, single-crystal investigation, Hirshfeld surface analysis and DFT inspection of the 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 2,4-dichlorobenzoate (1:1) (DECB). J. Mol. Struct., 2021, 1235, 130215. https://doi.org/10.1016/j.molstruc.2021.130215
H. Tanak, Y. Köysal, Y. Ünver, M. Yavuz, Ş. Işık, and K. Sancak. An experimental and DFT computational study on 4-(3-(1H-imidazol-1-yl)propyl)-5-methyl-2H-1,2,4-triazol-3(4H)-one monohydrate. Mol. Phys., 2010, 108(2), 127-139. https://doi.org/10.1080/00268970903535491
N. K. Kaynar, M. Yavuz, H. Tanak, S. Şahin, O. Büyükgüngör, and E. Ağar. Crystal structure of 2-((E)-(5-bromo-2-hydroxybenzylidene)hydrazono)-1,2-diphenylethanone. Crystallogr. Rep., 2018, 63(3), 375-378. https://doi.org/10.1134/s1063774518030136
H. Tanak, Y. Köysal, M. Yavuz, O. Büyükgüngör, and K. Sancak. Experimental and DFT computational studies on 5-benzyl-4-(3,4-dimethoxyphenethyl)-2H-1,2,4-triazol-3(4H)-one. J. Mol. Model., 2010, 16(3), 447-457. https://doi.org/10.1007/s00894-009-0559-1
H. Ünver, B. Boyacıoğlu, C. T. Zeyrek, M. Yıldız, N. Demir, N. Yıldırım, O. Karaosmanoğlu, H. Sivas, and A. Elmalı. Synthesis, spectral and quantum chemical studies and use of (E)-3-[(3,5-bis(trifluoromethyl)phenylimino)methyl]benzene-1,2-diol and its Ni(II) and Cu(II) complexes as an anion sensor, DNA binding, DNA cleavage, anti-microbial, anti-mutagenic and anti-cancer agent. J. Mol. Struct., 2016, 1125, 162-176. https://doi.org/10.1016/j.molstruc.2016.06.058
Ş. Atalay, S. Gerçeker, S. Meral, and H. Bülbül. 2-{(E)-[(3-chloro-4-methylphenyl)imino]methyl}-4-(trifluoromethoxy)phenol. IUCrData, 2017, 2(12), x171725. https://doi.org/10.1107/s2414314617017254
F. B. Kaynak, S. Özbey, and N. Karalı. Three novel compounds of 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone: Synthesis, crystal structures and molecular interactions. J. Mol. Struct., 2013, 1049, 157-164. https://doi.org/10.1016/j.molstruc.2013.06.039
S. Yeşilbağ, E. B. Çınar, N. Dege, E. Ağar, and E. Saif. Crystal structure and Hirshfeld surface analysis of dimethyl 3,3′-{[(1E,2E)-ethane-1,2-diylidene]bis(azanylylidene)}bis(4-methylbenzoate). Acta Crystallogr., Sect. E: Crystallogr. Commun., 2022, 78(4), 340-345. https://doi.org/10.1107/s2056989022002092
S. Demir Kanmazalp, O. E. Doĝan, V. Taşdemir, N. Dege, E. Aĝar, and I. O. Fritsky. Crystal structure and Hirshfeld surface analysis of a Schiff base: (Z)-6-[(5-chloro-2-methoxyanilino)methylidene]-2-hydroxycyclohexa-2,4-dien-1-one. Acta Crystallogr., Sect. E: Crystallogr. Commun., 2019, 75(3), 362-366. https://doi.org/10.1107/s2056989019002123
S. Kansiz, N. Dege, A. S. Aydin, E. Ağar, and I. P. Matushko. Crystal structure and Hirshfeld surface analysis of (Z)-6-[(2-hydroxy-5-nitroanilino)methylidene]-4-methylcyclohexa-2,4-dien-1-one. Acta Crystallogr., Sect. E: Crystallogr. Commun., 2019, 75(6), 812-815. https://doi.org/10.1107/s205698901900673x
N. Süleymanoğlu, R. Ustabaş, Ş. Direkel, Y. B. Alpaslan, and Y. Ünver. 1,2,4-triazole derivative with Schiff base; thiol-thione tautomerism, DFT study and antileishmanial activity. J. Mol. Struct., 2017, 1150, 82-87. https://doi.org/10.1016/j.molstruc.2017.08.075
R. Ustabaş, D. Ünlüer, and G. Kör. Crystal structure 4-(2,4-dihydroxybenzylideneamino)-5-methyl-2H-1,2,4-triazol-3(4H)-one. J. Chem. Crystallogr., 2011, 41(8), 1237-1240. https://doi.org/10.1007/s10870-011-0081-z
N. O. İskeleli, Y. B. Alpaslan, Ş. Direkel, A. G. Ertürk, N. Süleymanoğlu, and R. Ustabaş. The new Schiff base 4-[(4-hydroxy-3-fluoro-5-methoxy-benzylidene)amino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one: Experimental, DFT calculational studies and in vitro antimicrobial activity. Spectrochim. Acta, Part A, 2015, 139, 356-366. https://doi.org/10.1016/j.saa.2014.12.071
M. Turner, J. McKinnon, S. Wolff, D. Grimwood, P. Spackman, D. Jayatilaka, and M. Spackman. CrystalExplorer17. Perth, Australia: University of Western Australia 2017.
A. L. A. Kala, K. Kumara, N. V. Harohally, and N. K. Lokanath. Synthesis, characterization and hydrogen bonding attributes of halogen bonded O-hydroxy Schiff bases: Crystal structure, Hirshfeld surface analysis and DFT studies. J. Mol. Struct., 2020, 1202, 127238. https://doi.org/10.1016/j.molstruc.2019.127238
A. Masoudiasl, M. Montazerozohori, S. Joohari, L. Taghizadeh, G. Mahmoudi, and A. Assoud. Structural investigation of a new cadmium coordination compound prepared by sonochemical process: Crystal structure, Hirshfeld surface, thermal, TD-DFT and NBO analyses. Ultrason. Sonochem., 2019, 52, 244-256. https://doi.org/10.1016/j.ultsonch.2018.11.024
A. E. Reed and F. Weinhold. Natural bond orbital analysis of near-Hartree–Fock water dimer. J. Chem. Phys., 1983, 78(6), 4066-4073. https://doi.org/10.1063/1.445134
M. K. Abdel-Latif, H. R. Abd El-Mageed, H. S. Mohamed, and F. M. Mustafa. Study the solvation effect on 6-phenyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile derivatives by TD- DFT calculations and molecular dynamics simulations. J. Mol. Struct., 2020, 1200, 127056. https://doi.org/10.1016/j.molstruc.2019.127056
Z. Demircioğlu. Synthesis, crystal structure, spectroscopic characterization, chemical activity and molecular docking studies of (E)-2-(((3-chloro-4-methylphenyl)imino)methyl)-6-ethoxyphenol. J. Mol. Struct., 2021, 1246, 131114. https://doi.org/10.1016/j.molstruc.2021.131114
T. Koopmans. Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms. Physica, 1934, 1(1-6), 104-113. https://doi.org/10.1016/s0031-8914(34)90011-2
N. E. Eltayeb, F. Şen, J. Lasri, M. A. Hussien, S. E. Elsilk, B. A. Babgi, H. Gökce, and Y. Sert. Hirshfeld surface analysis, spectroscopic, biological studies and molecular docking of (4E)-4-((naphthalen-2-yl)methyleneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one. J. Mol. Struct., 2020, 1202, 127315. https://doi.org/10.1016/j.molstruc.2019.127315
T. S. Ganesan, N. Elangovan, V. Vanmathi, S. Sowrirajan, S. Chandrasekar, K. S. Murthy, and R. Thomas. Spectroscopic, computational (DFT), quantum mechanical studies and protein-ligand interaction of Schiff base 6,6-((1,2-phenylenebis(azaneylylidene))bis(methaneylylidene))bis(2-methoxyphenol) from o-phenylenediamine and 3-methoxysalicylaldehyde. J. Indian Chem. Soc., 2022, 99(10), 100713. https://doi.org/10.1016/j.jics.2022.100713
T. Vishwanath, A. Ashish, C. K. R. Shankar, and K. D. Amar. Single-crystal XRD, Hirshfeld surfaces, 3D energy framework calculations, and DFT studies of 4,5-diphenyl-1,3,4-thiadiazole-2-thiolate: A mesoionic compound. J. Mol. Struct., 2022, 1264, 133290. https://doi.org/10.1016/j.molstruc.2022.133290
F. Öztürk. Structural characterization (XRD, FTIR) and magnetic studies of Cd(II)-sulfamethoxazole-2,2′-bipyridine: DFT and Hirshfeld surface analysis. J. Mol. Struct., 2023, 1271, 133945. https://doi.org/10.1016/j.molstruc.2022.133945
H. Kargar, M. Fallah-Mehrjardi, R. Behjatmanesh-Ardakani, K. S. Munawar, M. Ashfaq, and M. N. Tahir. Diverse coordination of isoniazid hydrazone Schiff base ligand towards iron(III): Synthesis, characterization, SC-XRD, HSA, QTAIM, MEP, NCI, NBO and DFT study. J. Mol. Struct., 2022, 1250, 131691. https://doi.org/10.1016/j.molstruc.2021.131691
E. Güzel, Z. Demircioğlu, C. Çiçek, E. Ağar, and M. Yavuz. Experimental (XRD, FTIR, UV-Vis, NMR) and theoretical investigations (chemical activity descriptors, NBO, DNA/ECT) of (E)-2-((2-hydroxy-5-methoxybenzylidene)amino)-4-nitrophenol. Mol. Cryst. Liq. Cryst., 2021, 724(1), 58-76. https://doi.org/10.1080/15421406.2021.1905143
Z. Demircioğlu, G. Kaştaş, Ç. A. Kaştaş, and R. Frank. Spectroscopic, XRD, Hirshfeld surface and DFT approach (chemical activity, ECT, NBO, FFA, NLO, MEP, NPA & MPA) of (E)-4-bromo-2-[(4-bromophenylimino)methyl]-6-ethoxyphenol. J. Mol. Struct., 2019, 1191, 129-137. https://doi.org/10.1016/j.molstruc.2019.03.060
A. L. Murphree and W. F. Benedict. Retinoblastoma: Clues to human oncogenesis. Science, 1984, 223(4640), 1028-1033. https://doi.org/10.1126/science.6320372
M. Hassler, S. Singh, W. W. Yue, M. Luczynski, R. Lakbir, F. Sanchez-Sanchez, T. Bader, L. H. Pearl, and S. Mittnacht. Crystal structure of the retinoblastoma protein N domain provides insight into tumor suppression, ligand interaction, and holoprotein architecture. Mol. Cell, 2007, 28(3), 371-385. https://doi.org/10.1016/j.molcel.2007.08.023
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Text © The Author(s), 2024, published in Zhurnal Strukturnoi Khimii, 2024, Vol. 65, No. 1, 121415.https://doi.org/10.26902/JSC_id121415
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Suhta, A., Saral, S., Çoruh, U. et al. Synthesis, Single Crystal X-Ray, Hirshfeld Surface Analysis and DFT Calculation Based NBO, HOMO–LUMO, MEP, ECT and Molecular Docking Analysis of N′-[(2,6-Dichlorophenyl)Methylidene]-2-{[3-(Trifluoromethyl)Phenyl]Amino}Benzohydrazide. J Struct Chem 65, 196–215 (2024). https://doi.org/10.1134/S0022476624010189
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DOI: https://doi.org/10.1134/S0022476624010189