Mehmet BAĞLAN, Kenan GÖREN, Ümit YILDIKO

HOMO–LUMO, NBO, NLO, MEP analysis and molecular docking using DFT calculations in DFPA molecule

Using the Gaussian09 software package, N-(6-(2-(dimethylamino)ethoxy)-5-fluoropyridin-3-yl)-2-(4-fluorophenyl)-5-(trifluoromethyl)pyrazolo[1,5 α]pyrimidine-7-amine(DFPA) the theoretically optimal molecular structure, vibration frequencies and related vibrational movements of the molecule were researched. The DFT(B3PW91 and B3LYP) techniques' 6-311G(d,p) basis set was used to perform quantum chemical computations. HOMO and LUMO analysis were performed for charge transfer in the molecule. NBO analysis was used to examine the stability of the molecule as a result of both charge delocalization and hyperconjugative interaction. DFT approach was used to perform MEP and expected infrared sensitivities and Raman activity are also presented. Geometric parameters of both calculated DFT methods are compatible. Binding affinity values and molecular coupling studies show that the title substance forms a stable complex with MtPanK and PanK. It is possible that the molecule has inhibitory activity against MtPanK and PanK, paving the way for new anti-tuberculosis drugs’ the development.

Keywords:

DFPA, DFT MEP, NBO, Molecular Doking,

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1. Eun, H.-J.; Lee, J.; Kang, S.-J.; Lee, B.-J., The structural and functional investigation of the VapBC43 complex from Mycobacterium tuberculosis. Biochemical and Biophysical Research Communications 2022, 616, 19-25.
2. Fei, H.; Yinyin, X.; Hui, C.; Ni, W.; Xin, D.; Wei, C.; Tao, L.; Shitong, H.; Miaomiao, S.; Mingting, C.; Keshavjee, S.; Yanlin, Z.; Chin, D. P.; Jianjun, L., The impact of the COVID-19 epidemic on tuberculosis control in China. The Lancet Regional Health - Western Pacific 2020, 3, 100032.
3. Brennan, M. J.; Thole, J., Tuberculosis Vaccines: A Strategic Blueprint for the Next Decade. Tuberculosis 2012, 92, S6-S13.
4. Alame Emane, A. K.; Guo, X.; Takiff, H. E.; Liu, S., Highly transmitted M. tuberculosis strains are more likely to evolve MDR/XDR and cause outbreaks, but what makes them highly transmitted? Tuberculosis 2021, 129, 102092.
5. Ashenafi, S.; Muvva, J. R.; Mily, A.; Snäll, J.; Zewdie, M.; Chanyalew, M.; Rehn, A.; Rahman, S.; Aseffa, G.; Bekele, A.; Aderaye, G.; Lema, B.; Svensson, M.; Brighenti, S., Immunosuppressive Features of the Microenvironment in Lymph Nodes Granulomas from Tuberculosis and HIV–Co-Infected Patients. The American Journal of Pathology 2022, 192 (4), 653-670.
6. Swain, S. S.; Pati, S.; Hussain, T., Quinoline heterocyclic containing plant and marine candidates against drug-resistant Mycobacterium tuberculosis: A systematic drug-ability investigation. European Journal of Medicinal Chemistry 2022, 232, 114173.
7. Koirala, S.; Borisov, S.; Danila, E.; Mariandyshev, A.; Shrestha, B.; Lukhele, N.; Dalcolmo, M.; Shakya, S. R.; Miliauskas, S.; Kuksa, L.; Manga, S.; Aleksa, A.; Denholm, J. T.; Khadka, H. B.; Skrahina, A.; Diktanas, S.; Ferrarese, M., Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort. Pulmonology 2021, 27 (5), 403-412.
8. Global tuberculosis report 2020. World Health Organization 2020.
9. Choi, P. J.; Lu, G.-L.; Sutherland, H. S.; Giddens, A. C.; Franzblau, S. G.; Cooper, C. B.; Denny, W. A.; Palmer, B. D., Synthetic studies towards isomeric pyrazolopyrimidines as potential ATP synthesis inhibitors of Mycobacterium tuberculosis. Structural correction of reported N-(6-(2-(dimethylamino)ethoxy)-5-fluoropyridin-3-yl)-2-(4-fluorophenyl)-5-(trifluoromethyl)pyrazolo[1,5-α]pyrimidin-7-amine. Tetrahedron Letters 2022, 90, 153611.
10. Frisch MJ; Trucks GW; and SH; and GE. S, Gaussian 09. Revision E E.01.
11. Ahamed, J. I.; Narendran, K.; Ambika, V. R.; Priya, R.; Kamalarajan, P.; Sundareswaran, T.; Gunasekaran, B.; Jayalakshmi, S., Synthesis, spectral characterization, DFT-Computational analyses on Novel 4-nitrobenzenaminium benzenesulfonate (4NBASA) crystal. Journal of Molecular Structure 2022, 133548.
12. Mirnezhad, M.; Ansari, R.; Falahatgar, S. R.; Aghdasi, P., Torsional buckling analysis of MWCNTs considering quantum effects of fine scaling based on DFT and molecular mechanics method. Journal of Molecular Graphics and Modelling 2021, 104, 107843.
13. Geethapriya, J.; Shanthidevi, A.; Arivazhagan, M.; Elangovan, N.; Thomas, R., Synthesis, structural, DFT, quantum chemical modeling and molecular docking studies of (E)-4-(((5-methylfuran-2-yl)methylene)amino) benzenesulfonamide from 5-methyl-2-furaldehyde and sulfanilamide. Journal of the Indian Chemical Society 2022, 99 (4), 100418.
14. Abdou, A.; Mostafa, H. M.; Abdel-Mawgoud, A.-M. M., Seven metal-based bi-dentate NO azocoumarine complexes: Synthesis, physicochemical properties, DFT calculations, drug-likeness, in vitro antimicrobial screening and molecular docking analysis. Inorganica Chimica Acta 2022, 539, 121043.
15. Sucheta, M.; Pramod, A. G.; Zikriya, M.; Mohammed Salma, K.; Venugopal, N.; Chaithra, R.; Harshitha, D.; Amudan, S.; Renuka, C. G.; Murthy, S., Frontier molecular orbital, molecular structure and Thermal properties of 2,4,6,8-tetramethyl-2,3,6,7-tetrahydro-s-indacene-1,5-dione using DFT calculation. Materials Today: Proceedings 2022.
16. Mohapatra, R. K.; Perekhoda, L.; Azam, M.; Suleiman, M.; Sarangi, A. K.; Semenets, A.; Pintilie, L.; Al-Resayes, S. I., Computational investigations of three main drugs and their comparison with synthesized compounds as potent inhibitors of SARS-CoV-2 main protease (Mpro): DFT, QSAR, molecular docking, and in silico toxicity analysis. Journal of King Saud University - Science 2021, 33 (2), 101315.
17. Kanagathara, N.; Nanmaran, R., Illustration of potential energy surface from DFT calculation along with fuzzy logic modelling for optimization of N-acetylglycine. Computational and Theoretical Chemistry 2021, 1202, 113301.
18. Budania, S.; Saxena, S.; Jain, A., Assessment of DFT based optimized molecular structure-antioxidant efficacy relationship of trimethylgermanium(IV) complexes. Journal of the Indian Chemical Society 2022, 99 (5), 100419.
19. Raveendiran, C.; Prabukanthan, P.; Ragavendran, V.; Harichandran, G.; Dinakaran, K.; Seenuvasakumaran, P., Synthesis, crystal growth, crystal investigation, optical, thermal, DFT and NLO studies of 2-methylanilinium- 4-methylbenzenesulfonate organic single crystal: Experimental and computational approach. Materials Today: Proceedings 2022.
20. Muhammad, S., Symmetric vs. asymmetric: Which one is the better molecular configuration for achieving robust NLO response? Journal of Molecular Graphics and Modelling 2022, 114, 108209.
21. Krishna Kumar, V.; Sangeetha, R.; Barathi, D.; Mathammal, R.; Jayamani, N., Vibrational assignment of the spectral data, molecular dipole moment, polarizability, first hyperpolarizability, HOMO–LUMO and thermodynamic properties of 5-nitoindan using DFT quantum chemical calculations. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2014, 118, 663-671.
22. Karne, A. S.; Vaval, N.; Pal, S.; Vásquez-Pérez, J. M.; Köster, A. M.; Calaminici, P., Systematic comparison of DFT and CCSD dipole moments, polarizabilities and hyperpolarizabilities. Chemical Physics Letters 2015, 635, 168-173.
23. Kleinman, D. A., Phys. Rev. 1977-1979., 126 (1962).
24. Satheeshkumar, R.; Prabha, K.; Vennila, K. N.; Sayin, K.; Güney, E.; Kaminsky, W.; Acevedo, R., Spectroscopic (FT-IR, NMR, single crystal XRD) and DFT studies including FMO, Mulliken charges, and Hirshfeld surface analysis, molecular docking and ADME analyses of 2-amino-4′-fluorobenzophenone (FAB). Journal of Molecular Structure 2022, 133552.
25. Priya, M. K.; Revathi, B. K.; Renuka, V.; Sathya, S.; Asirvatham, P. S., Molecular Structure, Spectroscopic (FT-IR, FT-Raman, 13C and 1H NMR) Analysis, HOMO-LUMO Energies, Mulliken, MEP and Thermal Properties of New Chalcone Derivative by DFT Calculation. Materials Today: Proceedings 2019, 8, 37-46.
26. Demir, S.; Tinmaz, F.; Dege, N.; Ilhan, I. O., Vibrational spectroscopic studies, NMR, HOMO–LUMO, NLO and NBO analysis of 1-(2-nitrobenzoyl)-3,5-diphenyl-4,5-dihydro-1H-pyrazole with use X-ray diffractions and DFT calculations. Journal of Molecular Structure 2016, 1108, 637-648.
27. Sarojini, K.; Krishnan, H.; Kanakam, C. C.; Muthu, S., Synthesis, X-ray structural, characterization, NBO and HOMO–LUMO analysis using DFT study of 4-methyl-N-(naphthalene-1-yl)benzene sulfonamide. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2012, 96, 657-667.
28. Akintemi, E. O.; Govender, K. K.; Singh, T., A DFT study of the chemical reactivity properties, spectroscopy and bioactivity scores of bioactive flavonols. Computational and Theoretical Chemistry 2022, 1210, 113658.
29. TEKEŞ, A. T.; ATA, A. Ç.; TANRIVERDİ, A. A.; ÇAKMAK, İ. J. J. o. t. I. o. S.; Technology, Insilico Molecular Docking Studies of THBF Compound: TD-DFT Simulations and Drug Design. 2021, 11 (4), 2955-2966.
30. Jeeva Jasmine, N.; Thomas Muthiah, P.; Arunagiri, C.; Subashini, A., Vibrational spectra (experimental and theoretical), molecular structure, natural bond orbital, HOMO–LUMO energy, Mulliken charge and thermodynamic analysis of N′-hydroxy-pyrimidine-2-carboximidamide by DFT approach. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2015, 144, 215-225.
31. Balachandran, V.; Karunakaran, V., Quantum mechanical study of the structure and vibrational spectroscopic (FT-IR and FT-Raman), first-order hyperpolarizability, NBO and HOMO−LUMO studies of 4-bromo-3-nitroanisole. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2013, 106, 284-298.
32. Ulahannan, R. T.; Panicker, C. Y.; Varghese, H. T.; Musiol, R.; Jampilek, J.; Van Alsenoy, C.; War, J. A.; Srivastava, S. K., Molecular structure, FT-IR, FT-Raman, NBO, HOMO and LUMO, MEP, NLO and molecular docking study of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2015, 151, 184-197.
33. Isravel, A. D.; Jeyaraj, J. K.; Thangasamy, S.; John, W. J., DFT, NBO, HOMO-LUMO, NCI, stability, Fukui function and hole – Electron analyses of tolcapone. Computational and Theoretical Chemistry 2021, 1202, 113296.
34. Buvaneswari, M.; Santhakumari, R.; Usha, C.; Jayasree, R.; Sagadevan, S., Synthesis, growth, structural, spectroscopic, optical, thermal, DFT, HOMO–LUMO, MEP, NBO analysis and thermodynamic properties of vanillin isonicotinic hydrazide single crystal. Journal of Molecular Structure 2021, 1243, 130856.
35. Saravanan, R. R.; Seshadri, S.; Gunasekaran, S.; Mendoza-Meroño, R.; Garcia-Granda, S., Conformational analysis, X-ray crystallographic, FT-IR, FT-Raman, DFT, MEP and molecular docking studies on 1-(1-(3-methoxyphenyl) ethylidene) thiosemicarbazide. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2015, 139, 321-328.
36. Sakr, M. A. S.; Saad, M. A., Spectroscopic investigation, DFT, NBO and TD-DFT calculation for porphyrin (PP) and porphyrin-based materials (PPBMs). Journal of Molecular Structure 2022, 1258, 132699.
37. Aboalhassan, A. A.; El-Daly, S. A.; Ebeid, E.-Z. M.; Sakr, M. A. S., 1,4-bis[β-(2-benzoxazoly1) vinyl] benzene (BBVB) laser dye and sodium salt of meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS); spectroscopic investigation and DFT, NBO and TD-DFT calculations. Journal of Photochemistry and Photobiology A: Chemistry 2022, 431, 114039.
38. Kaya, E. D.; Türkhan, A.; Gür, F.; Gür, B. J. J. o. B. S.; Dynamics, A novel method for explaining the product inhibition mechanisms via molecular docking: inhibition studies for tyrosinase from Agaricus bisporus. 2021, 1-14.
39. Ulahannan, R. T.; Panicker, C. Y.; Varghese, H. T.; Musiol, R.; Jampilek, J.; Alsenoy, C. V.; War, J. A.; Manojkumar, T. K., Vibrational spectroscopic studies and molecular docking study of 2-[(E)-2-phenylethenyl]quinoline-5-carboxylic acid. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2015, 150, 190-199.