Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analyses
This work presents an extensive computational investigation of the molecular structure and characteristics of molecule (E)-4-(4-(1-(2-(4-(4-nitrophenyl)thiazol-2-yl)hydrazineylidene)ethyl)phenyl)morpholine. Using Density Functional Theory (DFT) with the B3LYP functional and 6–311++G(d,p) basis set,...
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Elsevier
2025-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624006477 |
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| author | Vishnu A. Adole I.Antony Danish J.Jebasingh Kores J.Winfred Jebaraj S. Janani Suresh K. Ghotekar Rakesh D. Amrutkar |
| author_facet | Vishnu A. Adole I.Antony Danish J.Jebasingh Kores J.Winfred Jebaraj S. Janani Suresh K. Ghotekar Rakesh D. Amrutkar |
| author_sort | Vishnu A. Adole |
| collection | DOAJ |
| description | This work presents an extensive computational investigation of the molecular structure and characteristics of molecule (E)-4-(4-(1-(2-(4-(4-nitrophenyl)thiazol-2-yl)hydrazineylidene)ethyl)phenyl)morpholine. Using Density Functional Theory (DFT) with the B3LYP functional and 6–311++G(d,p) basis set, the molecular structure, Frontier Molecular Orbitals (FMOs), Natural Bond Orbital (NBO) interactions, Noncovalent Interactions (NCI), and stability were investigated. An energy gap (ΔE) of 2.92 eV was found by the FMO analysis, indicating a moderate degree of stability and chemical reactivity. Important information about intramolecular charge transfer (ICT) was revealed by the NBO analysis. Significant interactions between the donor and acceptor, namely involving LP(3)N25 → σ*C24-C26, were confirmed by second-order perturbation energies, yielding a stabilization energy of 12.54 kcal/mol. Significant van der Waals contacts were shown by the NCI analysis, particularly between the thiazole and phenyl rings, indicating regions of steric hindrance. UV–Vis, IR, and NMR simulations were used to forecast spectroscopic characteristics. The functional groups in titled compound were identified using infrared spectroscopy (IR). Chemical shifts were precisely assigned using Nuclear Magnetic Resonance (NMR) analysis. Furthermore, the ADME analysis predicted favorable pharmacokinetic properties. With a zone of inhibition of 10.87 mm, the thiazole derivative demonstrated substantial antifungal effectiveness against Aspergillus flavus. The molecular docking analysis revealed titled compound had a significant interaction with cytochrome P450 EryK. Significant hydrogen and hydrophobic contacts were observed in this interaction, which led to a docking score of −5.28 and a binding free energy of −65.65 kcal/mol. |
| format | Article |
| id | doaj-art-5e1492ec10b144fea72ea21e7ba1851e |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-5e1492ec10b144fea72ea21e7ba1851e2025-01-29T05:00:40ZengElsevierResults in Chemistry2211-71562025-01-0113101951Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analysesVishnu A. Adole0I.Antony Danish1J.Jebasingh Kores2J.Winfred Jebaraj3S. Janani4Suresh K. Ghotekar5Rakesh D. Amrutkar6Department of Chemistry, Mahatma Gandhi Vidyamandir’s Loknete Vyankatrao Hiray Arts, Science and Commerce College, Panchavati, Nashik, Maharashtra 422003, India1; Corresponding authors.Department of Chemistry, Sadakathullah Appa College (Autonomous), Tirunelveli, Tamilnadu 627011, India2Department of Physics, Pope’s College (Autonomous), Sawyerpuram, Tamilnadu 628251, India2Department of Chemistry, St. John’s College, Tirunelveli, Tamilnadu 627002, India2; Corresponding authors.Department of Physics, Meenakshi College for Women, Kodambakkam, Chennai, Tamil Nadu 600024, India3Centre for Herbal Pharmacology and Environmental Sustainability, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu 603103, IndiaDepartment of Pharmaceutical Chemistry, K. K. Wagh College of Pharmacy Panchavati, Nashik, Maharashtra 422003, IndiaThis work presents an extensive computational investigation of the molecular structure and characteristics of molecule (E)-4-(4-(1-(2-(4-(4-nitrophenyl)thiazol-2-yl)hydrazineylidene)ethyl)phenyl)morpholine. Using Density Functional Theory (DFT) with the B3LYP functional and 6–311++G(d,p) basis set, the molecular structure, Frontier Molecular Orbitals (FMOs), Natural Bond Orbital (NBO) interactions, Noncovalent Interactions (NCI), and stability were investigated. An energy gap (ΔE) of 2.92 eV was found by the FMO analysis, indicating a moderate degree of stability and chemical reactivity. Important information about intramolecular charge transfer (ICT) was revealed by the NBO analysis. Significant interactions between the donor and acceptor, namely involving LP(3)N25 → σ*C24-C26, were confirmed by second-order perturbation energies, yielding a stabilization energy of 12.54 kcal/mol. Significant van der Waals contacts were shown by the NCI analysis, particularly between the thiazole and phenyl rings, indicating regions of steric hindrance. UV–Vis, IR, and NMR simulations were used to forecast spectroscopic characteristics. The functional groups in titled compound were identified using infrared spectroscopy (IR). Chemical shifts were precisely assigned using Nuclear Magnetic Resonance (NMR) analysis. Furthermore, the ADME analysis predicted favorable pharmacokinetic properties. With a zone of inhibition of 10.87 mm, the thiazole derivative demonstrated substantial antifungal effectiveness against Aspergillus flavus. The molecular docking analysis revealed titled compound had a significant interaction with cytochrome P450 EryK. Significant hydrogen and hydrophobic contacts were observed in this interaction, which led to a docking score of −5.28 and a binding free energy of −65.65 kcal/mol.http://www.sciencedirect.com/science/article/pii/S2211715624006477Computational chemistrySpectroscopic analysisFrontier molecular orbitalsADME profilingAntifungal studyMolecular docking |
| spellingShingle | Vishnu A. Adole I.Antony Danish J.Jebasingh Kores J.Winfred Jebaraj S. Janani Suresh K. Ghotekar Rakesh D. Amrutkar Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analyses Results in Chemistry Computational chemistry Spectroscopic analysis Frontier molecular orbitals ADME profiling Antifungal study Molecular docking |
| title | Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analyses |
| title_full | Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analyses |
| title_fullStr | Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analyses |
| title_full_unstemmed | Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analyses |
| title_short | Computational and experimental exploration of morpholine pendent 2-hydrazineyl thiazole: Insights from DFT, ADME profiling, antifungal efficacy and molecular docking analyses |
| title_sort | computational and experimental exploration of morpholine pendent 2 hydrazineyl thiazole insights from dft adme profiling antifungal efficacy and molecular docking analyses |
| topic | Computational chemistry Spectroscopic analysis Frontier molecular orbitals ADME profiling Antifungal study Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624006477 |
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