Theoretical (DFT, molecular docking and ADME) and experimental studies (XRD, UV-Vis, NMR, FT-IR) of (E)-4-bromo-2-(((4-bromo-2(trifluoromethyl)phenyl)imino) methyl)phenol (I) and (E)-2-(((4-bromo-2-(trifluoromethyl) phenyl)imino)methyl)-5-methoxyphenol (II)
JOURNAL OF MOLECULAR STRUCTURE, cilt.1381, 2027 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1381
- Basım Tarihi: 2027
- Doi Numarası: 10.1016/j.molstruc.2026.147552
- Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Ondokuz Mayıs Üniversitesi Adresli: Evet
Özet
Two Schiff base derivatives, namely (E)-4-bromo-2-(((4-bromo-2(trifluoromethyl)phenyl)imino)methyl)phenol (I) and (E)-2-(((4-bromo-2-(trifluoromethyl)phenyl)imino)methyl)-5-methoxyphenol (II), were synthesized and characterized. The title structures were confirmed by X-ray diffraction, FT-IR, UV-Vis, NMR analyses. Hirshfeld surface analysis and interaction energy calculations demonstrated that electrostatic and hydrogen-bond contributions govern crystal packing, leading to efficiently stabilized lattice. In both molecules were stabilized by a strong intramolecular O-H...N hydrogen bond, supporting the enol-imine tautomeric form. All theoretical analyses were calculated by the density functional theory DFT/B3LYP/6-311G(d,p) basis set. The calculated results showed that the optimized geometry could well reproduce the crystal structural paramaters. For both molecules, frontier molecular orbital (FMO) energies and chemical descriptors were calculated, and it was found that the molecules possess good stability, lower softness, higher chemical hardness, and high energy gaps. MEP, fukui function and net atomic charge analyses further supported electronic delocalization and reactive site distribution for (I) and (II). The hyperconjugative interactions and stabilization energy of the compounds was estimated via NBO analysis. Molecular docking analysis was performed to investigate the interaction between the compounds and the "beta 3 adrenergic receptor" (9IJD) ADRB3. The binding free energy of (II) was -7.8 kcal/mol, with suitable RMSD limits (1,665-2,120 & Aring;), while these values for (I) were -5.4 kcal/mol and 1,872-2,620 & Aring;, respectively. Therefore, molecular docking and ADME calculations were examined in detail for (II). The calculated ADME analysis was consistent with Lipinski's Five Rules, Ghose, Veber, Egan, and Muegge drug-likeness criteria, and predicts that the drug possesses favorable physicochemical and pharmacokinetic properties. We predict that molecular modeling and ADME analyses will provide a basis for potential drug-likeness characteristics of Schiffbased molecules with beta 3 adrenergic receptor.