Synthesis, spectroscopy, crystal structure, TGA/DTA study, DFT and molecular docking investigations of (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one

Abstract

In this study, we present the synthesis of novel pyridazin-3(2H)-one derivative namely (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one (MBSP). The chemical structure of MBSP was characterized using spectroscopic techniques such as FT-IR, ¹H NMR, ¹³C NMR, UV-Vis, ESI-MS, and finally, the structure was confirmed by single X-ray diffraction studies. The DFT calculation was performed to compare the gas-phase geometry of the title compound to the solid-phase structure of the title compound. Furthermore, a comparative study between theoretical UV-Vis, IR, ¹H- and ¹³C NMR spectra of the studied compound and experimental ones have been carried out. The thermal behavior and stability of the compound were analyzed by using TGA and DTA techniques which revealed that the compound is thermostable up to its melting point. Finally, the in silico docking and ADME studies are performed to investigate whether MBSP is a potential therapeutic for COVID-19.

Keywords: Crystal structure, DFT, Hirshfeld surface; Molecular docking; Pyridazin-3(2h)-one; Synthesis; Thermal analysis.

Fig. 1

Example of drugs with pyridazinone ring.

Fig. 2

The molecular structure of MBSP, with atom labeling. Displacement ellipsoids are drawn at the 40% probability level (a), visualizing of dihedral angles within the molecule (b).

Fig. 3

Packing diagrams with intermolecular interactions of the title compound.

Fig. 4

The B3LYP-optimized geometries of the title compound (bond lengths in Å; nitrogen in blue, oxygen in red, carbon in gray, hydrogen in white).

Fig. 5

The molecular electrostatic potential for MBSP (the isodensity value= 0.0004).

Fig. 6

Experimental (a) and simulated (b) FT-IR spectra of the title compound.

Fig. 7

Experimental (a) and simulated (b) UV–vis spectra of the title compound.

Fig. 8

The frontier orbitals of MBSP (the isodensity value = 0.02).

Fig. 9

The experimental (a) ¹H and (b) ¹³C NMR spectra of MBSP.

Fig. 10

d_norm mapped on Hirshfeld surfaces for visualizing the interactions of the title compound.

Fig. 11

Curvedness and shape indexes are shown for MBSP.

Fig. 12

Fingerprint plots of the whole molecules and the most effective interactions.

Fig. 13

TGA, DTA, and DrTGA curves of the title compound.

Fig. 14

The results of the docking studies of MBSP concerning the chosen targets.

Fig. 14

The results of the docking studies of MBSP concerning the chosen targets.

Fig. 15

The possible targets of MBSP.

Fig. 16

The SwissADME result.

Scheme 1

Synthetic route of (MBSP).