4-(5-metil-[1, 2, 4] triazolo [1, 5-a] pirimidin-7-iloksi) ftalonitrilin Yapısal ve Spektral Özellikleri: TD-DFT Yöntemi ile Analizi, ADME analizi ve Moleküler Doking Simülasyonları

Abstract

Bu çalışmada ftalonitril bileşiği ve kuantum kimyasalı olarak 4-(5-metil-[1,2,4]triazolo[1,5-a]pirimidin-7-iloksi)ftalonitril (MTPPN olarak kodlanmıştır) seçilmiştir ve in-siliko çalışmalar yapılmıştır. İlk başta zamana bağlı yoğunluk fonksiyonel teorisi (TD-DFT) yönteminin temel seti kullanılmış ve molekülün sınır yörünge enerjileri ve bant aralığı hesaplamaları yapılmıştır. Elektron yoğunluğu ve bağ kritik nokta hakkında bilgi edinmek için moleküllerdeki atomların analizi (AIM) teorik hesaplamaları sunulmaktadır. Ayrıca bileşiğin ilaç potansiyeli için absorpsiyon, dağılım, metabolizma ve atılım (ADME) analizleri yapıldı. MTPPN bileşiğinin bazı enzimler üzerindeki etkisi incelenmiştir. Yerleştirme puanı sırasıyla AChE, BChE, a-GLY proteinleri -7.864, -6.848 ve -5.511 kcal/mol için elde edilmiştir. MTPPN, bir ilaç adayı olarak in-siliko bir çalışmada iyi bir inhibitör performans göstermiştir.

Keywords

• Ftalonitril
• moleküler doking
• ADME
• TD-DFT
• AIM

Structural and Spectral Properties of 4-(5-methyl-[1, 2, 4] triazolo [1, 5-a] pyrimidine-7-yloxy) phthalonitrile: Analysis by TD-DFT Method, ADME Analysis, and Molecular Docking Simulations

Abstract

In this study, 4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-7-yloxy) phthalonitrile (coded as MTPPN) was chosen as the phthalonitrile compound and the quantum chemical and in-silico studies have been done. First, the basis set of the time dependent density functional theory (TD-DFT) method was used and the boundary orbital energies and band gap calculations of the molecule were performed. Analysis of atoms in molecules (AIM) theoretical calculations is presented to learn about electron density and bond critical point. In addition, absorption, distribution, metabolism, and excretion analyzes (ADME) were performed for the drug potential of the compound. On some enzymes effect of MTPPN compound was examined. The docking score was obtained for AChE, BChE, α-GLY proteins -7.864, -6.848, and -5.511 kcal/mol, respectively. MTPPN gave a good inhibitory performance in an in-silico study as a drug candidate.

Keywords

• Phthalonitrile
• ADME
• TD-DFT
• AIM
• molecular docking

References

1. Abdelhady AM, Yin H, Rodriguez Lorenc K, Ji Y, 2019. Clinical Pharmacokinetics (ADME). Clinical Pharmacology in Drug Development 8 (S1): 1-101. Agirtas MS, Ondes MY, Ozdemir S and Okumus V, 2017. DNA cleavage properties and synthesis of metallophthalocyanines with 5-methyl-[1, 2, 4] triazolo [1, 5-a] pyrimidin-7-oxy substituents. Inorganic and Nano-Metal Chemistry, 47 (7): 1097-1102.
2. Altun K, Yildiko U, Tanriverdi AA, Cakmak I, 2021. Structural and spectral properties of 4-(4-(1-(4-Hydroxyphenyl)-1-phenylethyl) phenoxy) phthalonitrile: Analysis by TD-DFT method, ADME analysis and docking studies. International Journal of Chemistry and Technology, 5 (2):147-155.
3. Bernetti M, Cavalli A and Mollica L, 2017. In Medchemcomm pp. 534-550.
4. Bulat FA, Chamorro E, Fuentealba P and Toro-Labbé A, 2004. Condensation of Frontier Molecular Orbital Fukui Functions. The Journal of Physical Chemistry A, 108 (2): 342-349.
5. BIOVIA Discovery Studio D. SYSTÈMES BIOVIA Corporate Europe 2016, BIOVIA 334 Cambridge Science Park Cambridge CB4 0WN, England http://accelrys.com/products/collaborative-science/biovia-discovery-studio/
6. De Lile JR, Kang SG, Son YA and Lee SG, 2020. Do HOMO–LUMO Energy Levels and Band Gaps Provide Sufficient Understanding of Dye-Sensitizer Activity Trends for Water Purification? ACS Omega, 5 (25): 15052-15062.
7. Demircioglu Z, Kastas CA and Buyukgungor O, 2015. Theoretical analysis (NBO, NPA, Mulliken Population Method) and molecular orbital studies (hardness, chemical potential, electrophilicity and Fukui function analysis) of (E)-2-((4-hydroxy-2-methylphenylimino)methyl)-3-methoxyphenol. Journal of Molecular Structure, 1091 (5): 183-195.
8. Daina A, Michielin O, Zoete V, 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7: 42717.

9. Dong Q, Hu N, Yue H, Wang H, 2021. Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel α-Glucosidase Inhibitor. Molecules, 26 (15) :4566.
10. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich AV, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery Jr. JA, Peralta JE, Ogliaro F, Bearpark MJ, Heyd JJ, Brothers EN, Kudin KN, Staroverov VN, Keith TA, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ, 2016. Gaussian 16 Rev. C.01, Wallingford, CT.
11. Hashimoto H, Hattori K, Yamada T and Kobayashi T, 2001. Electro-Absorption Spectroscopy And Semi-Empirical Molecular Orbital Calculations Of Polar Retinoid Analogues. International Journal of Modern Physics B, 15 (28n30): 3773-3776.
12. Ilyas RA, Sapuan SM, Asyraf MRM, Dayana DAZN, Amelia JJN, Rani MSA, Norrrahim MN, Nurazzi NM, Aisyah HA, Sharma S, Ishak MR, Rafidah M and Razman MR, 2021. Polymer Composites Filled with Metal Derivatives: A Review of Flame Retardants. Polymers, 13 (11): 1701.
13. Ledoux I and Zyss J, 1994. Nonlinear Organic Molecules And Materials For Optoelectronic Devices. Journal of Nonlinear Optical Physics & Materials, 03 (03): 287-316.
14. Lin J, Sahakian DC, de Morais SM, Xu JJ, Polzer RJ and Winter SM, 2003. The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery. Current topics in medicinal chemistry, 3 (10): 1125-1154.
15. Liu H, Zhang H, Xu X and Zhang L, 2021. The Opto-Electronic Functional Devices Based on Three-Dimensional Lead Halide Perovskites. Applied Sciences, 11 (4) 1453.
16. Madakbaş S, Çakmakçı E and Kahraman MV, 2013. Preparation and thermal properties of polyacrylonitrile/hexagonal boron nitride composites. Thermochimica Acta, 552: 1-4.
17. Madhavi Sastry G, Adzhigirey M, Day T, Annabhimoju R, Sherman W, 2013. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27: 221-234.
18. Mendiratta S, Lee C-H, Usman M and Lu K-L, 2015. Metal-organic frameworks for electronics: emerging second order nonlinear optical and dielectric materials. Science and Technology of Advanced Materials, 16 (5): 054204-054204.
19. Nemykin VN and Lukyanets EA, 2010. Synthesis of substituted phthalocyanines. ARKIVOC, 2010 (1): 136-208.
20. Nisha CM, Kumar A, Nair P, Gupta N, Silakari C, Tripathi T and Kumar A, 2016. Molecular Docking and In Silico ADMET Study Reveals Acylguanidine 7a as a Potential Inhibitor of β-Secretase. Advances in Bioinformatics, 2016: 9258578.
21. Oida, 2006. In Optica Industry Report. Optica, 2006 pp. 3.
22. Pathak S, Saha GC, Abdul Hadi MB and Jain NK, 2021. Engineered Nanomaterials for Aviation Industry in COVID-19 Context: A Time-Sensitive Review. Coatings, 11 (4): 382.
23. Pendás ÁM, Gatti C, 2021. 3 Quantum theory of atoms in molecules and the AIMAll software. Complementary Bonding Analysis, 43. https://doi.org/10.1515/9783110660074-003
24. Priya Madhuri K and John NS, 2022. In Design, Fabrication, and Characterization of Multifunctional Nanomaterials, ed. S. Thomas, N. Kalarikkal and A.R. Abraham. Elsevier, pp. 401-448.
25. Tan M, Temel S, 2012. Alternative Feed Crops. Ataturk University Agricultural Faculty Course Publications No: 246, pp. 195-207, Erzurum-Turkey.
26. Tekes AT, Ata AC, Tanriverdi AA, Cakmak I, 2021. Insilico Molecular Docking Studies of THBF Compound: TD-DFT Simulations and Drug Design. Journal of the Institute of Science and Technology, 11 (4): 2955-2966.
27. Van Mourik T, Buhl M and Gaigeot MP, 2014. Density functional theory across chemistry, physics and biology. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 372 (2011): 20120488-20120488.
28. Weinhold F, 2012. Natural bond critical point analysis: Quantitative relationships between natural bond orbital-based and QTAIM-based topological descriptors of chemical bonding. Journal of Computational Chemistry, 33 (30): 2440-2449.
29. Yang Y, Díaz Palencia JL, Wang N, Jiang Y and Wang DY, 2021. Nanocarbon-Based Flame Retardant Polymer Nanocomposites. Molecules (Basel, Switzerland), 26 (15): 4670.
30. Yankova R, Genieva S, Halachev N and Dimitrova G, 2016. Molecular structure, vibrational spectra, MEP, HOMO-LUMO and NBO analysis of Hf(SeO3)(SeO4)(H2O)4. Journal of Molecular Structure, 1106: 82-88.
31. Yildiko U and Tanriverdi AA, 2021. Synthesis and characterization of pyromellitic dianhydride based sulfonated polyimide: Survey of structure properties with DFT and QTAIM. Journal of Polymer Research, 29 (1): 19.
32. Zangwill A, 2014. The education of Walter Kohn and the creation of density functional theory. Archive for History of Exact Sciences, 68 (6): 775-848.