Hidrazin Türevi Bir Schiff Baz Bileşiğinin DFT ve in Silico ADME/T Hesaplamaları

Year 2025, Volume: 15 Issue: 3, 1264 - 1280, 15.09.2025

Gonca Özdemir Tarı

https://doi.org/10.31466/kfbd.1692215

Abstract

Bu çalışma, daha önce X-ışını kristalografisi ile yapısı belirlenen hidrazin türevi bir Schiff baz bileşiğinin elektronik ve yapısal özelliklerinin Yoğunluk Fonksiyonel Teorisi (DFT) ile B3LYP/B3PW91 yöntemleri ve 6-31G++(d,p) temel baz seti ile incelenmesini içermektedir. Gaussian 03 programı kullanılarak gerçekleştirilen bu çalışmada, bileşiğin optimize geometrisi, öncü moleküler orbital enerjileri, moleküler elektrostatik potansiyel haritası, atomik yük dağılımları ve Fukui fonksiyonları belirlenmiştir. Çizgisel olmayan optik özelliklerin elde edilen yüksek β değeri bileşiğin etkili bir optik malzeme adayı olduğunu kanıtlar niteliktedir. Molekülün farmakokinetik ve toksisite özelliğe sahip olup olmadığını değerlendirmek amacıyla in silico ADME/T analizleri gerçekleştirilmiştir. Sonuç olarak, teorik çalışmaların sonuçları ile deneysel sonuçlar oldukça uyumlu olup bileşiğin elektronik yapısı ve reaktivitesi hakkında önemli bilgiler sunmaktadır.

Keywords

Schiff Bazı , DFT Hesaplamaları , ADME/T Tahmini , Kimyasal Reaktivite

DFT and in silico ADME/T Calculations of a Hydrazine Derivative Schiff Base Compound

Abstract

This study includes the investigation of the electronic and structural properties of a hydrazine-derived Schiff base compound, whose structure was previously determined by X-ray crystallography, using Density Functional Theory (DFT) with the B3LYP/B3PW91 methods and 6-31G++(d,p) basis set. The optimized geometry of the compound, frontier molecular orbital energies, molecular electrostatic potential (MEP) map, atomic charge distributions, and Fukui functions were determined using the Gaussian 03 software. The high β value obtained for nonlinear optical (NLO) properties demonstrates that the compound is a promising candidate for optical materials. In silico ADME/T analyses were performed to evaluate the pharmacokinetic and toxicity properties of the molecule. In conclusion, the results of the theoretical studies are in good agreement with the experimental data and provide valuable insights into the electronic structure and reactivity of the compound.

Keywords

Schiff Base , DFT Calculations , ADME/T Prediction , Chemical Reactivity

References

• Akbari, Z., Stagno, C., Iraci, N., Efferth, T., Omer, E. A., Piperno, A., ... & Micale, N. (2024). Biological evaluation, DFT, MEP, HOMO-LUMO analysis and ensemble docking studies of Zn (II) complexes of bidentate and tetradentate Schiff base ligands as antileukemia agents. Journal of Molecular Structure, 1301, 137400.
• Albaaj, L. T. T., Hassan, Q. M., Dhumad, A. M., Sultan, H. A., & Emshary, C. A. (2024). Synthesis of a New Schiff Base: Nonlinear Optical Properties Investigations. Journal of Fluorescence, 1-14.
• Banerjee, P., Kemmler, E., Dunkel, M., & Preissner, R. (2024). ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 52(W1), W513-W520.
• Berber, H., & Uysal, Ü. D. (2021). 2-((2-Hidroksibenziliden)amino)-4-Nitrofenol Schiff Bazının Teorik Olarak İncelenmesi ve Bazı Quantum Kimyasal Parametrelerinin Hesaplanması. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 25(3), 685-698.
• Daina, A., & Zoete, V. (2016). A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem, 11(11), 1117-1121.
• Dilek, Ö. (2024). Imidazole Based Novel Schiff Base: Synthesis, Characterization, Quantum Chemical Calculations, In Silico Investigation of ADMEt Properties and Molecular Docking Simulations against VEGFR2 Protein. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, 13(1), 134–148.
• Dennigton R. II, T. Keith, J. Millam, GaussView, Version 4.1.2, Semichem, Inc., Shawnee Mission, KS, 2007.
• Ejidike, I. P., Direm, A., Parlak, C., Adeniyi, A. A., Azam, M., Ata, A., ... & Clayton, H. S. (2024). Spectroscopic characterization, DFT calculations, in vitro pharmacological potentials, and molecular docking studies of N, N, O-Schiff base and its trivalent metal complexes. Chemical Physics Impact, 8, 100549.
• Eryilmaz, S., Gul, M., & Ozek Yildirim, A. (2024). Evaluation of Novel Hydrazone‐Imide Hybrid Compound as HNE Inhibitor In Silico: Synthesis, XRD and DFT Analysis. ChemistrySelect, 9(31), e202401982.
• Inac, H., Ashfaq, M., Dege, N., Feizi-Dehnayebi, M., Munawar, K. S., Yağcı, N. K., ... & Tahir, M. N. (2024). Synthesis, spectroscopic characterizations, single crystal XRD, supramolecular assembly inspection via hirshfeld surface analysis, and DFT study of a hydroxy functionalized schiff base Cu (II) complex. Journal of Molecular Structure, 1295, 136751.
• Frisch M. J. et al., Gaussian 03, Revision E.01, Gaussian, Inc., Wallingford CT, 2004.
• Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26.
• Özdemir Tarı G., Karadeniz Fen Bilimleri Dergisi, 12(1), 178-192, 2022. DOI: 10.31466/kfbd.1008650.
• Gören, K., Bağlan, M., Yıldıko, Ü. ve Tahiroğlu, V. (2024). Anti-Kanser ve Anti-Üreaz Aktivitesi için Tiazolidinon-Bis Schiff Bazının Moleküler Yerleştirme ve DFT Analizi. Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 14(2), 822-834.
• Kirca, B. K., Tari, G. Ö., Kaştaş, C. A., Odabaşoğlu, M., & Büyükgüngör, O. (2017). Crystal structure, spectral characterization, molecular modeling studies and structural effects of the proton transfer process for (E)-5-methoxy-2-[(3, 4-dimethylphenylimino) methyl] phenol. Macedonian Journal of Chemistry and Chemical Engineering.
• Mirdan, G. A., Hassan, Q., Kadhum, M. Y., Emshary, C. A., Hussein, K. A., Sultan, H. A., ... & Abdullmajed, H. A. (2025). Study of DFT, synthesis, and nonlinear optical properties of a Schiff base compound. Journal of Fluorescence, 1-14.
• Salihović, M., Pazalja, M., Halilović, S. Š., Veljović, E., Mahmutović-Dizdarević, I., Roca, S., ... & Trifunović, S. (2021). Synthesis, characterization, antimicrobial activity and DFT study of some novel Schiff bases. Journal of molecular structure, 1241, 130670.
• Sarıoğlu, A. O., Türkmenoğlu, B., Kahraman, D. T., Güler, S., Sürmelihindi, B., & Morcali, M. H. (2025). Transition metal complexes of sulfonamide-based schiff base ligand: Synthesis, characterization, a biological assessment, DFT, and ADME studies. Journal of Molecular Structure, 1325, 140907.
• SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. (2017) 7:42717.
• Padariya, A. D., Savaliya, N. K., Parekh, H. M., Bhatt, B. S., Bhatt, V. D., & Patel, M. N. (2025). Synthesis, characterization, and biological activities of novel organometallic compounds of rhenium (I) with 2-(2-benzylidenehydrazinyl) benzothiazole Schiff-base derivatives: Molecular docking, ADME, and DFT studies. Computational Biology and Chemistry, 115, 108313.
• Tahir, M. N., Ashfaq, M., Munawar, K. S., Khan, A. U., Asghar, M. A., Ahamad, T., & Ojha, S. C. (2024). Synthesis, characterizations, Hirshfeld surface analysis, DFT, and NLO study of a schiff base derived from trifluoromethyl amine. ACS omega, 9(2), 2325-2338.
• Tarı, G. Ö. (2024). Pirazol türevı bir bileşiğin kuramsal hesaplamaları ve hirshfeld yüzey analizi. Kahramanmaraş Sütçü İmam Üniversitesi Mühendislik Bilimleri Dergisi, 27(2), 447-458.
• Tarı, G. Ö., & Aydemir, E. (2023). Experimental and DFT study of (E)-4-bromo-2 (((3-chloro-4-(4-chlorophenoxy) phenyl) imino) methyl)-5-fluorophenol: Molecular and electronic properties in solvent media. Journal of Molecular Structure, 1277, 134880.
• Tarı, G. Ö., & Demirtaş, G. 2-(2-İyodofenil) isoindolin-1, 3-dion) Molekülünün Hesaplamalı Kimya Yöntemiyle Yapısal Analizi. International Journal of Multidisciplinary Studies and Innovative Technologies, 6(1), 91-96.
• Tarı, G. Ö. (2023). Synthesis, structural characterization by experimental and theoretical approaches of a new hydrazine derivative Schiff base compound. Molecular Crystals and Liquid Crystals, 766(1), 131-155.
• Tarı, G. Ö., & Demirtaş, G. (E)-5-Fenil-N-(2-tiyenilmetilen)-1, 3, 4-tiyadiazol-2-amin’in Hirshfeld Yüzey Analizi ve Teorik Hesaplamaları. Avrupa Bilim ve Teknoloji Dergisi, (32), 761-769, 2021.
• Uzun S. & Demircioğlu Z, Karadeniz Fen Bilimleri Dergisi, (2019) 9(2), 275-288. DOI: 10.31466/kfbd.611312.