2-okso-2-feniletil 3-nitroso-2-fenilimidazo[1,2-a]piridin-8-karboksilat bileşiğinin DFT çalışmaları

Year 2025, Volume: 13 Issue: 3, 1072 - 1088, 31.07.2025

Cemile Baydere Demir

https://doi.org/10.29130/dubited.1552103

Abstract

Bu çalışma da, başlık bileşiği 2-okso-2-feniletil 3-nitroso-2-fenilimidazo[1,2-a]piridin-8-karboksilat (PIP) spektroskopik olarak değerlendirildi. Moleküler geometri (bağ uzunluğu, bağ açısı), elektronik özellikler (elektronegatiflik, kimyasal potansiyel, global sertlik, global yumuşaklık), en yüksek dolu moleküler orbital (HOMO) ve en düşük boş moleküler orbital (LUMO), Mulliken atom yükü, yoğunluk fonksiyonel teorisi DFT/B3LYP yöntemi 6−311G++(d,p) teori seviyesi kullanılarak hesaplandı. Moleküler elektrostatik potansiyel (MEP), sınır moleküler orbitaller (FMO), Mulliken yüklerinin DFT hesaplamaları, bu molekülün kimyasal reaktifliğinden sorumlu kimyasal olarak aktif bölgelerini tanımlar. Doğal bağ orbital (NBO) analizi, moleküler sistemlerde moleküller arası ve molekül içi bağ, yük transferi ve hiperkonjugatif etkileşimlerin araştırılması için etkili bir metodoloji sunar. Uyarılmış durumlar ve absorpsiyon karakteristikleri hakkında bilgi elde etmek için B3LYP/6–311G++(d,p) teori düzeyinde TD–DFT hesaplamaları yapıldı.

Keywords

İmidazo [1 , 2-a] piridin , DFT metodu , HOMO , LUMO enerjileri

Supporting Institution

Bu çalışma Ondokuz Mayıs Üniversitesi tarafından PYO FEN.1906.19.001 nolu proje kapsamında desteklenmiştir.

DFT studies of 2-oxo-2-phenylethyl 3-nitroso-2-phenylimidazo[1,2-a]pyridine-8-carboxylate compound

Abstract

In the study, the title compound 2-oxo-2-phenylethyl 3-nitroso-2-phenylimidazo[1,2-a]pyridine-8-carboxylate (PIP) was deliberated spectroscopically. Molecular geometry (bond length, bond angle), electronic properties (electronegativity, chemical potential, global hardness, global softness), the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), Mulliken atomic charge were calculated using the density functional theory DFT/B3LYP method 6−311G++(d,p) level of theory. DFT calculations of the molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), Mulliken charges recognize the chemically active sites of this molecule responsible for its chemical reactivity. The natural bond orbital (NBO) analysis gives an efficient methodology for investigating the inter- and intramolecular bonding, charge transfer and hyperconjugative interactions in molecular systems. TD–DFT calculations were performed at the B3LYP/6–311G++(d,p) level of theory to obtain information about excited states and absorption characteristics.

Keywords

İmidazo[1 , 2-a]pyridine , DFT method , HOMO , LUMO energies

References

• [1] T. Swainston Harrison, & G. M. Keating, “Zolpidem: a review of its use in the management of insomnia,” CNS Drugs, vol. 19, pp. 65–89, 2005.
• [2] A. Deep, R. K. Bhatia, R. Kaur, S. Kumar, U. K. Jain, H. Singh, S. Batra, D. Kaushik, & P. K. Deb, “Imidazo [1, 2-a] pyridine scaffold as prospective therapeutic agents,” Current Topics in Medicinal Chemistry, vol. 17, no. 2, pp. 238–250, 2017.
• [3] N. P. Mishra, S. Mohapatra, C. R. Sahoo, B. P. Raiguru, S. Nayak, S. Jena, & R. N. Padhy, “Design, one-pot synthesis, molecular docking study, and antibacterial evaluation of novel 2H-chromene based imidazo[1,2-a]pyridine derivatives as potent peptide deformylase inhibitors,” Journal of Molecular Structure, 1246, 131183, 2021.
• [4] A. Wang, K. Lv, L. Li, H. Liu, Z. Tao, B. Wang, M. Liu, C. Ma, X. Ma, B. Han, A. Wang, & Y. Lu, “Design, synthesis and biological activity of N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamides as new antitubercular agents,” European Journal of Medicinal Chemistry, vol. 178, pp. 715–725, 2019.
• [5] T. Damghani, S. Hadaegh, M. Khoshneviszadeh, S. Pirhadi, R. Sabet, M. Khoshneviszadeh, & N. Edraki, “Design, synthesis, in vitro evaluation and molecular docking study of N'-Arylidene imidazo [1,2-a] pyridine -2-carbohydrazide derivatives as novel Tyrosinase inhibitors,” Journal of Molecular Structure, 1222, 128876, 2020.
• [6] M. L. Bode, D. Gravestock, S. S. Moleele, C. W. van der Westhuyzen, S. C. Pelly, P. A. Steenkamp, H. C. Hoppe, T. Khan, & L. A. Nkabinde, “Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors,” Bioorganic & Medicinal Chemistry, vol. 19, pp. 4227–4237, 2011.
• [7] M. Saeedi, M. Raeisi-Nafchi, S. Sobhani, S. S. Mirfazli, M. Zardkanlou, S. Mojtabavi, M. A. Faramarzi, & T. Akbarzadeh, “Synthesis of 4-alkylaminoimidazo[1,2-a]pyridines linked to carbamate moiety as potent α-glucosidase inhibitors,” Molecular Diversity, vol. 25, pp. 2399–2409, 2021.
• [8] G. B. Gundlewad, S. S. Wagh, & B. R. Patil, “Catalyst and Solvent Free Synthesis and Biological Activities of Imidazo [1, 2-a] pyridine,” Asian Journal of Organic Medicinal Chemistry, vol. 5, pp. 221–226, 2020.
• [9] Y. N. Yu, Y. Han, F. Zhang, Z. Gao, T. Zhu, S. Dong, & M. Ma, “Design, Synthesis, and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel PI3K/mTOR Dual Inhibitors,” Journal of Medicinal Chemistry, vol. 63, pp. 3028–3046, 2020.
• [10] D. K. Sigalapalli, G. Kiranmai, G. Parimala Devi, R. Tokala, S. Sana, C. Tripura, G. S. Jadhav, M. Kadagathur, N. Shankaraiah, N. Nagesh, B. N. Babu, & N. D. Tangellamudi, “Synthesis and biological evaluation of novel imidazo[1,2-a]pyridine-oxadiazole hybrids as anti-proliferative agents: Study of microtubule polymerization inhibition and DNA binding,” Bioorganic & Medicinal Chemistry, vol. 43, 116277, 2021.
• [11] A. K. Bagdi, S. Santra, K. Monir, A. Hajra, “Synthesis of imidazo[1,2-a]pyridines: a decade update,” Chemical Communications, vol. 51, pp. 1555-1575, 2015.
• [12] V. Kurteva, “Recent Progress in Metal-Free Direct Synthesis ofImidazo[1,2‑a]pyridines,” ACS Omega, vol. 6, pp. 35173-35185, 2021.
• [13] E. Kraka, & D. Cremer, “Computer design of anticancer drugs,” Journal of the American Chemical Society, vol. 122, pp. 8245–8264, 2000.
• [14] F. Jensen, “Atomic orbital basis sets,” Wiley Interdisciplinary Reviews: Computational Molecular Science, vol. 3(3), pp. 273–295, 2012. [15] W. J. Hehre, R. F. Stewart, and J. A. Pople, “ Self‐Consistent Molecular‐Orbital Methods. I. Use of Gaussian Expansions of Slater‐Type Atomic Orbitals,” Journal of Chemical Physics, vol. 51(6), pp. 2657-2664, 1969.
• [16] J. S. Binkley, J. A. Pople, and W. J. Hehre, “ Self-consistent molecular orbital methods. 21. Small split-valence basis sets for first-row elements,” Journal of the American Chemical Society, vol. 102(3), pp. 939-947, 1980.
• [17] R. Ditchfield, W. J. Hehre, and J. A. Pople, “Self‐Consistent Molecular‐Orbital Methods. IX. An Extended Gaussian‐Type Basis for Molecular‐Orbital Studies of Organic Molecules,” Journal of Chemical Physics, vol. 54(2), pp. 724-728, 1971.
• [18] W. J. Hehre, R. Ditchfield, and J. A. Pople, “Self—Consistent Molecular Orbital Methods. XII. Further Extensions of Gaussian—Type Basis Sets for Use in Molecular Orbital Studies of Organic Molecules,” Journal of Chemical Physics, vol. 56(5), pp. 2257-2261, 1972.
• [19] P. C. Hariharan and J. A. Pople, “The influence of polarization functions on molecular orbital hydrogenation energies,” Theoretica Chimica Acta, vol. 28, pp. 213-222, 1973.
• [20] J. D. Dill, J. A. Pople, “Self‐consistent molecular orbital methods. XV. Extended Gaussian‐type basis sets for lithium, beryllium, and boron,” Journal of Chemical Physics, vol. 62(7), pp. 2921-2923, 1975.
• [21] H.A. Khamees, K. Chaluvaiah, N.A. El-khatatneh, A. Swamynayaka, K.H. Chong, J.P. Dasappa, M. Madegowda, “ Crystal structure, DFT calculation, Hirshfeld surface analysis and energy framework study of 6-bromo-2-(4-bromophenyl)imidazo[1,2-a]pyridine,” Acta Crystallographica Section, E75, pp. 1620-1626, 2019.
• [23] A. E. Aatıaouı, M. Koudad, T. Chelfi, S., Erkan, M. Azzouzı, A. Aounıtı, K. Savaş, M Kaddourı, N. Benchat, A. Oussaıd, “Experimental and theoretical study of new Schiff bases based on Imidazo(1,2-a)pyridine as corrosion inhibitor of mild steel in 1M HCl,” Journal of Molecular Structure, 1226, 129372, 2021.
• [23] D. Chen, Y. Chen, Q. Wu, X. Zhang, W. Liao, & Z. Zhou, “Synthesis, crystal structure and vibrational properties of N-(8-(3-(3-(tert-butyl)ureido)phenyl)imidazo[1,2-a]pyridin-6-yl)acetamide,” Journal of Molecular Structure, 1245, 131101, 2021.
• [24] H. Chen, Y. Wang, Q. Liu, Y. Guo, S. Cao, Y. Zhao, “ Synthesis and Evaluation of Photophysical Properties of C-3 Halogenated Derivatives of 2-Phenylimidazo[1,2-a]pyridine,” Chinese Journal of Chemistry, vol. 40, pp. 2313-2328, 2022.
• [25] S. Wang, Y. Chen, D. Chen, W. Ye, L. Yao, Z. Huang, Z. Zhou, “Synthesis, crystal structure and vibrational properties studies of ( S )- N -(1-phenylethyl)-6-(4-(trifluoromethoxy)phenyl)imidazo[1,2- a ]pyridine-2-carboxamide,” Journal of Molecular Structure, 1272, 134175, 2023.
• [26] M. Azzouzi, Z. E. Ouafi, O. Azougagh, W. Daoudi, H. Ghazal, S. E. Barkany, R. Adderrazak, S. Mazières, A. E. Aatiaoui, A. Oussaid, “Design, synthesis, and computational studies of novel imidazo[1,2-a]pyrimidine derivatives as potential dual inhibitors of hACE2 and spike protein for blocking SARS-CoV-2 cell entry,” Journal of Molecular Structure, 1285, 135525, 2023.
• [27] M. Azzouzi, O. Azougagh, A. A. Ouchaoui, S. eddine El hadad, S. Mazières, S. El Barkany, M. Abboud and A. Oussaid, “Synthesis, Characterizations and Quantum Chemical Investigations on Imidazo[1,2‑a]pyrimidine-Schiff Base Derivative: (E)‑2-Phenyl‑N‑(thiophen 2ylmethylene)imidazo[1,2‑a]pyrimidin-3-amine,” ACS Omega, vol. 9, pp. 837–857, 2024.
• [28] W. Song, L. Li, L. Ma, Z. Yang, Z. Zheng, Z. Zhou, “Synthesis, crystal structure, DFT, vibrational properties, Hirshfeld surface and antitumor activity studies of a new compound 2-(2-chloro-6-(m-tolyl) imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide,” Journal of Molecular Structure, 1307, 138052, 2024.
• [29] F. E. Kalai, C. Baydere, N. Dege, A. Abudunia, N. Benchat, K. Karrouchi, “Crystal structure and Hirshfeld surface analysis of 2-oxo-2-phenylethyl 3-nitroso-2-phenylimidazo-[1,2-a]pyridine-8-carboxylate,” Acta Crystallographica Section, E78, pp. 322-325, 2022.
• [30] S. Cie, X-area (Version 1.18) and X-Red 32, version 1.04, Darmstadt Ger., 2004.
• [31] G. M. Sheldrick, “SHELXT: integrating space group determination and structure solution,” Acta Crystallographica Section A: Foundations and Advances, 70, C1437, 2014.
• [32] C. F. Macrae , I. J. Bruno , J. A. Chisholm , P. R. Edgington , P. McCabe , E. Pidcock , L. Rodriguez-Monge , R. Taylor , J. van de Streek , P. A. Wood , “Mercury CSD 2.0-new features for the visualization and investigation of crystal structures,” Journal of Applied Crystallography, vol. 41, pp. 466–470, 2008.
• [33] A. Spek, “Single-crystal structure validation with the program PLATON,” Journal of Applied Crystallography, vol. 36, pp. 7–13, 2003.
• [34] L. J. Farrugia , “WinGX suite for small-molecule single-crystal crystallography,” Journal of Applied Crystallography, vol. 32, pp. 837–838, 1999.
• [35] S. P. Westrip, “publCIF: software for editing, validating and formatting crystallographic information files,” Journal of Applied Crystallography, vol. 43, pp. 920–925, 2010.
• [36] Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., et al. (2013). Gaussian 09 (Revision D.01). Gaussian, Inc.
• [37] R. Dennington, T. Keith, J. Millam, “GaussView, Version 5”, Semichem Inc., Shawnee Mission KS, 2010.
• [38] A. D. Becke, “Density-functional exchange-energy approximation with correct asymptotic behavior,” Physical Review A, vol. 38(6), pp. 3098-3100, 1988.
• [39] C. Lee, W. Yang, R. G. Parr, “Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density,” Physical Review B, vol. 37, pp. 785–789, 1988.
• [40] E. D. Glendening, A. E. Reed, J. E. Carpenter, F. Weinhold, NBO Version 3.1, TCI, University of Wisconsin, Madison, 1998.
• [41] N. Islam, S. Kaya, “Conceptual Density Functional Theory and its Application in the Chemical Domain,” CRC Press, 2018.
• [42] N. A. Ancın, S. G. Öztaş¸ , Ö. Küçükterzi, N. A. Öztaş¸ “Theoretical investigation of Ntrans cinnamylidene-m-toluidine by DFT method and molecular docking studies,” Journal of Molecular Structure, 1198, 126868, 2019.
• [43] P. K. Chattaraj, & D. R. Roy, “Update 1 of: Electrophilicity Index,” Chemical Reviews, vol. 107(9), pp. 46-74, 2007.
• [44] R. G. Parr, L. v Szentpaly, S. Liu, “Electrophilicity index,” Journal of the American Chemical Society, vol. 121, pp. 1922-1924, 1999.
• [45] E. Scrocco, J. Tomasi, “Electronic Molecular Structure, Reactivity and Intermolecular Forces: An Euristic Interpretation by Means of Electrostatic Molecular Potentials,” In Advances in Quantum Chemistry; Löwdin, P.-O., Ed.; Academic Press: New York, NY, USA, vol. 11, pp. 115–193, 1978.
• [46] K. Parimala, V. Balachandran, “Structural study, NCA, FT-IR, FT-Raman spectral investigations, NBO analysis and thermodynamic properties of 2', 4'- difluoroacetophenone by HF and DFT calculations,” Spectrochimica Acta, vol. 110, pp. 269–284, 2013.
• [47] P. G. Patil, R. Melavanki, S. B. Radder, R. Kusanur, C. S. Hiremath, N. R. Patil, S. M. Hiremath, “Synthesis, Structural Characterizations and Quantum Chemical Investigations on 1-(3-Methoxyphenyl)-3-naphthalen-1-yl-propenone,” ACS Omega, vol. 6, pp. 25982−25995, 2021.