Crystal structure, intermolecular interactions, Hirshfeld surface analysis, theoretical studies and biological evaluation of (E)-5-(benzyloxy)-2-{[(2,5-dimethoxyphenyl)imino]methyl}phenol, a new Schiff base.
TL;DR
Results indicate an enzyme-dependent inhibitory profile rather than uniformly superior activity relative to the reference inhibitors, and quantum theory of atoms in molecules (QTAIM) analysis was performed to characterize selected intra- and intermolecular interactions.
Abstract
In the present work, we report on the synthesis, characterization and biological evaluation of (E)-5-(benzyloxy)-2-{[(2,5-dimethoxyphenyl)imino]methyl}phenol Schiff base, C22H21NO4 (BDIMPh). The compound was synthesized via the condensation reaction between 4-benzyloxy-2-hydroxybenzaldehyde and 2,4-dimethoxyaniline. It was characterized using 1H, 13C NMR and FT-IR spectroscopies, and its crystal structure was determined by single-crystal X-ray crystallography. BDIMPh crystallizes with two crystallographically independent molecules in the asymmetric unit. The structural model also includes the reported disorder features, which are discussed on the basis of the crystallographic refinement. The two molecules of BDMPh have the same E configuration about the C=N bond. In the crystal, the independent molecules are linked to their inversion-related molecule via C-H...O hydrogen bonds. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to quantify the intermolecular contacts present in the crystal. Quantum theory of atoms in molecules (QTAIM) analysis was performed to characterize selected intra- and intermolecular interactions. The optimized geometry showed good agreement with the experimental X-ray crystal structure. The antioxidant activity of BDIMPh was evaluated using the DPPH and ABTS radical-scavenging assays. BDIMPh exhibited moderate radical-scavenging activity under the experimental conditions and showed higher IC50 values than the reference antioxidants. The enzyme inhibitory activity of BDIMPh was investigated against acetylcholinesterase (AChE), glutathione S-transferase (GST), α-glucosidase and tyrosinase. BDIMPh exhibited measurable enzyme-dependent inhibitory activity against AChE, GST and α-glucosidase, whereas comparatively weak inhibition was observed against tyrosinase. The IC50 values were 2.899 ± 0.851 µM for AChE, 3.850 ± 0.721 µM for GST and 3.284 ± 0.738 µM for α-glucosidase. Compared with the corresponding reference inhibitors, BDIMPh showed a slightly higher IC50 value than donepezil for AChE, a slightly lower IC50 value than ethacrynic acid for GST and a higher IC50 value than acarbose for α-glucosidase. These results indicate an enzyme-dependent inhibitory profile rather than uniformly superior activity relative to the reference inhibitors.