Computational studies of 2-(4-oxo-3-phenylthiazolidin-2-ylidene)malononitrile

Abstract

The molecular structure of the 2-(4-oxo-3-phenylthiazolidin-2-ylidene) malononitrile (3) is calculated using DFT B3LYP/6-311G(d, p) method. The calculated geometric parameters are in good agreement with the experimental data. The NBO calculations were performed to predict the natural atomic charges at the different atomic sites and study the different intramolecular charge transfer (ICT) interactions occurring in the studied system. The BD(2)C17-C19 → BD*(2)C14-C15, LP(2)O2 → BD*(1)N5-C9 and LP(1)N5 → BD*(2)C10-C11 ICT interactions causing stabilization of the system by 23.30, 30.63 and 52.48 kcal/mol, respectively. The two intense electronic transition bands observed experimentally at 249 nm and 296 nm are predicted using the TD-DFT calculations at 237.9 nm (f = 0.1618) and 276.4 nm (f = 0.3408), respectively. These electronic transitions are due to H-3 → L (94%) and H → L (95%) excitations, respectively.

Keywords: DFT/B3LYP calculations; Molecular docking; NBO calculations; Thiazole.

Fig. 1

a Synthesis of thiazole derivative 3 [9]. b Optimized chemical structure of the malononitrile analogue

Fig. 2

The molecular electrostatic potentials map predicted for the malononitrile analogue

Fig. 3

Electronic density surface plots at ground state for the FMOs of thiazole based malononitrile analogue. The molecular orbitals level are delocalized over the five member thiazole ring and the attached cyanate groups. Green represent negative values of the orbital overlap, dark red represents positive values of the orbitals overlap [50]

Fig. 4

2D representation showing the hydrogen bond interactions of the interesting compound and the targeting enzyme

Fig. 5

3D representation of the selected compound pose fitted inside the targeted enzyme

Fig. 6

Pharmacophore annotations of the malononitrile analogue