Exploring weak intermolecular interactions in two bis-1,3,4-oxadiazoles derivatives: A combined X-ray diffraction, Hirshfeld surface analysis and theoretical studies

ANDLEEB, HINA; SHAH, SYED WADOOD ALI; GIL, DIEGO M.; AHMED, MUHAMMAD NAEEM; SHEIKHI, MASOOME; TAHIR, MUHAMMAD NAWAZ; NADEEM, KOMAL; MAJEED, ZAHID; ROCHA, MARIANA

JOURNAL OF MOLECULAR STRUCTURE

ELSEVIER SCIENCE BV

Año: 2021 vol. 1232 p. 130030 - 130045

0022-2860

Two new bis-1,3,4-oxadiazole derivatives have been synthesized and characterized. The crystal structure of both compounds were solved by single crystal X-ray diffraction analysis and a detailed quantitative analysis of the weak non-covalent interactions have been performed by using the Hirshfeld surface analysis and DFT calculations. The results indicate that both molecules showed different crystal packing. Compound 1 shows C-H···N and C-H···O hydrogen bonds and the structure is also stabilized by C-H···π, π···π stacking and lone pair (S)···π interactions, while the crystal structure of 2 is mainly stabilized by C-H···N and weak C-H···S contacts. The Hirshfeld surfaces, QTAIM analysis and NCI plots were used to study the nature and the extent of different intermolecular interactions observed in these structures. The AChE inhibitory activity of 1 and 2 was evaluated with reference to standard drug Galantamine. The AChE inhibitory activity of compound 1 showed better inhibitory activity (IC50 = 36.34 µg/mL) as compared to compound 2 (IC50 = 47.34 µg/mL). The molecular docking analysis of the inhibitors was performed to identify the putative binding modes and interactions inside the active pocket of the enzymes. This analysis also indicates that the studied compounds could act as ?bulky?-blockers of the normal ionic substrate (ACh) entrance into the active site gorge of AChE.