The reactivity and stability of seventeen (17) imidazo [1,2-a]pyridine N-acylhydrazone derivatives were investigated using density functional theory at the B3LYP/6-31+ G (d, p) level. Analysis of the molecular electrostatic potential (MEP) and determination of the dual descriptor revealed that in most cases, the nitrogen atoms of the 6-πelectron conjugation, the oxygen, and the sulfur atom are nucleophilic site. Chemical reactivity of the compounds was assessed through analysis of frontier molecular orbitals (HOMO and LUMO), energy gap (
), chemical hardness (η), and the softness (S). Consequently, the compound 9e exhibited the lowest reactivity, least electron donating, and the highest stability. This comprehensive study offers valuable insights into the chemical behavior of these derivatives, crucial for further exploration and potential applications.
References
[1]
Rozada, A.M., Rodrigues, F.A., Sampiron, E.G., Seixas, F.A., Basso, E.A., Scodro, R.B., et al. (2019) Novel 4-Methoxynaphthalene-n-Acylhydrazones as Potential for Paracoccidioidomycosis and Tuberculosis Co-Infection. Future Microbiology, 14, 587-598. https://doi.org/10.2217/fmb-2018-0357
[2]
Velezheva, V., Brennan, P., Ivanov, P., Kornienko, A., Lyubimov, S., Kazarian, K., et al. (2016) Synthesis and Antituberculosis Activity of Indole-Pyridine Derived Hydrazides, Hydrazide-Hydrazones, and Thiosemicarbazones. Bioorganic & Medicinal Chemistry Letters, 26, 978-985. https://doi.org/10.1016/j.bmcl.2015.12.049
[3]
De Miranda, A., Júnior, W., Da Silva, Y., Alexandre-Moreira, M., Castro, R., Sabino, J., et al. (2012) Design, Synthesis, Antinociceptive and Anti-Inflammatory Activities of Novel Piroxicam Analogues. Molecules, 17, 14126-14145. https://doi.org/10.3390/molecules171214126
[4]
Morjan, R.Y., Mkadmh, A.M., Beadham, I., Elmanama, A.A., Mattar, M.R., et al. (2014) Antibacterial Activities of Novel Nicotinic Acid Hydrazides and Their Conversion into N-acetyl-1,3,4-oxadiazoles. Bioorganic & Medicinal Chemistry Letters,24, 5796-5800.
[5]
Ajani, O.O., Iyaye, K.T., Audu, O.Y., Olorunshola, S.J., Kuye, A.O. and Olanrewaju, I.O. (2018) Microwave Assisted Synthesis and Antimicrobial Potential of Quinoline-Based 4-Hydrazide-Hydrazone Derivatives. Journal of Heterocyclic Chemistry, 55, 302-312.
[6]
Rohane, S.H., Chauhan, A.J., Fuloria, N.K. and Fuloria, S. (2020) Synthesis and in Vitro Antimycobacterial Potential of Novel Hydrazones of Eugenol. Arabian Journal of Chemistry, 13, 4495-4504. https://doi.org/10.1016/j.arabjc.2019.09.004
[7]
Chezal, J., Paeshuyse, J., Gaumet, V., Canitrot, D., Maisonial, A., Lartigue, C., et al. (2010) Synthesis and Antiviral Activity of an Imidazo[1,2-A]pyrrolo[2,3-C]pyridine Series against the Bovine Viral Diarrhea Virus. European Journal of Medicinal Chemistry, 45, 2044-2047. https://doi.org/10.1016/j.ejmech.2010.01.023
[8]
Chitti, S., Singireddi, S., Santosh Kumar Reddy, P., Trivedi, P., Bobde, Y., Kumar, C., et al. (2019) Design, Synthesis and Biological Evaluation of 2-(3,4-Dimethoxyphenyl)-6 (1,2,3,6-Tetrahydropyridin-4-Yl)imidazo[1,2-A]pyridine Analogues as Antiproliferative Agents. Bioorganic & Medicinal Chemistry Letters, 29, 2551-2558. https://doi.org/10.1016/j.bmcl.2019.08.013
[9]
Nasr, T., Bondock, S. and Youns, M. (2014) Anticancer Activity of New Coumarin Substituted Hydrazide-Hydrazone Derivatives. European Journal of Medicinal Chemistry,76, 539-548.
[10]
Morcoss, M., Abdelhafez, E.S., Abdel-Rahman, H., Abdel-Aziz, M. and Abou El-Ella, D. (2020) Novel Benzimidazole/Hydrazone Derivatives as Promising Anticancer Lead Compounds: Design, Synthesis, and Molecular Docking Study. Journal of Advanced Biomedical and Pharmaceutical Sciences, 3, 45-52.
[11]
Cikla, P., Küçükgüzel, G., Küçükgüzel, İ., Rollas, S., De Clercq, E., Pannecouque, C., et al. (2010) Synthesis and Evaluation of Antiviral, Antitubercular and Anticancer Activities of Some Novel Thioureas Derived from 4-Aminobenzohydrazide Hydrazones. Marmara Pharmaceutical Journal,14, 13-20.
[12]
Reddy Gangireddy, M., Mantipally, M., Gundla, R., Nayak Badavath, V., Paidikondala, K. and Yamala, A. (2019) Design and Synthesis of Piperazine-Linked Imidazo[1,2-a]pyridine Derivatives as Potent Anticancer Agents. ChemistrySelect, 4, 13622-13629. https://doi.org/10.1002/slct.201902955
[13]
Şenkardeş, S., Kaushik-Basu, N., Durmaz, İ., Manvar, D., Basu, A., Atalay, R., et al. (2016) Synthesis of Novel Diflunisal Hydrazide-Hydrazones as Anti-Hepatitis C Virus Agents and Hepatocellular Carcinoma Inhibitors. European Journal of Medicinal Chemistry, 108, 301-308. https://doi.org/10.1016/j.ejmech.2015.10.041
[14]
Ablo, E., Coulibaly, S., Coulibali, S., Signo, K., Achi, P., Giraud, N., et al. (2022) Synthesis and Characterization of Novel Conformers of (e)-2-(3-nitro-h-imidazo[1,2-a]pyridin-2-ylthio)-n’-benzylideneacetohydrazide Derivatives. Magnetic Resonance in Chemistry, 60, 1157-1170. https://doi.org/10.1002/mrc.5308
Hohenberg, P. and Kohn, W. (1964) Inhomogeneous Electron Gas. Physical Review, 136, B864-B871. https://doi.org/10.1103/physrev.136.b864
[17]
Dennington, R., Keith, T. and Millam, J. (2009) GaussView, Version 5. Semichem Inc.
[18]
Koch, W. and Holthausen, M.C. (2001) A Chemist’s Guide to Density Functional Theory. 2nd Edition, Wiley.
[19]
N’dri, J., Koné, M., Kodjo, C., kablan, A., Affi, S., Ouattara, L., et al. (2018) Theoretical Study of the Chemical Reactivity of Five Schiff Bases Derived from Dapsone by the DFT Method. Chemical Science International Journal, 22, 1-11. https://doi.org/10.9734/csji/2018/41427
Labet, V. (2009) Etude Théorique de Quelques Aspects de La Réactivité Des Bases de l’ADN-Définition de Nouveaux Outils Théoriques d’étude de La Réactivité Chimique. Thèse de doctorat, Université Joseph-Fourier-Grenoble.
[22]
Sanderson, R.T. (1951) An Interpretation of Bond Lengths and a Classification of Bonds. Science, 114, 670-672. https://doi.org/10.1126/science.114.2973.670
[23]
Parr, R.G. and Pearson, R.G. (1983) Absolute Hardness: Companion Parameter to Absolute Electronegativity. Journal of the American Chemical Society, 105, 7512-7516. https://doi.org/10.1021/ja00364a005
[24]
Yang, W. and Parr, R.G. (1985) Hardness, Softness, and the Fukui Function in the Electronic Theory of Metals and Catalysis. Proceedings of the National Academy of Sciences of the United States of America, 82, 6723-6726.
[25]
Pearson, R.G. (1963) Hard and Soft Acids and Bases. Journal of the American Chemical Society, 85, 3533-3539. https://doi.org/10.1021/ja00905a001
[26]
Koopmans, T. (1934) Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms. Physica, 1, 104-113. https://doi.org/10.1016/s0031-8914(34)90011-2
[27]
Fukui, K., Yonezawa, T. and Shingu, H. (1952) A Molecular Orbital Theory of Reactivity in Aromatic Hydrocarbons. The Journal of Chemical Physics, 20, 722-725. https://doi.org/10.1063/1.1700523
[28]
Morell, C., Grand, A. and Toro-Labbé, A. (2005) New Dual Descriptor for Chemical Reactivity. The Journal of Physical Chemistry A,109, 205-212.
[29]
Wang, B., Rong, C., Chattaraj, P.K. and Liu, S. (2019) A Comparative Study to Predict Regioselectivity, Electrophilicity and Nucleophilicity with Fukui Function and Hirshfeld Charge. Theoretical Chemistry Accounts, 138, Article No. 124. https://doi.org/10.1007/s00214-019-2515-1
[30]
Stalke, D. (2011) Meaningful Structural Descriptors from Charge Density. Chemistry—A European Journal, 17, 9264-9278.
[31]
Tuo, N.T., Dembele, G.S., Doh, S., Konate, F., Konate, B., Kodjo, C.G., et al. (2022) Theoretical Study of the Chemical Reactivity of a Series of 2,3-Dihydro-1h-perimidine. International Research Journal of Pure and Applied Chemistry, 23, 13-25. https://doi.org/10.9734/irjpac/2022/v23i130451
