Structural and theoretical analysis, molecular docking/dynamics investigation of 3-(1-m-chloridoethylidene)-chromane-2,4‑dione: The role of chlorine atom

• DOI: 10.1016/j.molstruc.2021.129962
• Publication Date: 2021-01-20T13:29:01Z
• Authors: Edina H. Avdović; Dušan S. Dimić; Marek Fronc; Jozef Kožišek; Erik Klein; Žiko B. Milanović; Ana Kesić; Zoran S. Marković
• Keywords: Natural bond orbital; Reactivity; Docking (animal); Derivative (finance)

Abstract The coumarin derivative, 3-(1-m-chloridoethylidene)-chroman-2,4‑dione, was previously synthesized by a conventional method. Detailed structural characterization of the obtained compound was performed by using X-ray crystallography and vibrational analysis. Experimental data were confirmed by the optimization of a structure employing three common functionals (B3LYP-D3BJ, M06–2X, and APF-D) in combination with a 6–311+G(d,p) basis set. Low values of the average absolute error and the high values of the correlation coefficient for bond lengths and angles, proved that B3LYP-D3BJ could be used for the structural and spectral analysis. The stability of the investigated compound was determined by Fukui functions, NBO, and QTAIM analyses along with various reactivity parameters. The special emphasis in the discussion was put on the role of a chlorine atom for the overall stability and reactivity by comparison with 3-(1-(phenylamino)ethylidene)-chromane-2,4‑dione. In silico simulations with Adenosine A2a receptors (ADORA2A), were performed using molecular docking and dynamics methods for both coumarin derivatives. The thermodynamic parameters and specific interactions proved the importance of chlorine atom for possible biological activity.