Crystal structure, Hirshfeld surface analysis, DFT and molecular docking studies of ethyl 5-amino-2-bromoisonicotinate

Abstract

In the title compound, C8H9BrN2O2, the C—O—C—C torsion angle between isonicotine and the ethyl group is 180.0 (2)°. Intramolecular N—H...O and C—H...O interactions consolidate the molecular structure. In the crystal, N—H...N interaction form S(5) zigzag chains along [010]. The most significant contributions to the Hirshfeld surface arise from H...H (33.2%), Br...H/H...Br (20.9%), O...H/H...O (11.2%), C...H/H...C (11.1%) and N...H/H...N (10%) contacts. The topology of the three-dimensional energy frameworks was generated using the B3LYP/6–31 G(d,p) model to calculate the total interaction energy. The net interaction energies for the title compound are Eele = 59.2 kJ mol−1, Epol = 15.5 kJ mol−1, Edis = 140.3 kJ mol−1 and Erep = 107.2 kJ mol−1 with a total interaction energy Etot of 128.8 kJ mol−1. The molecular structure was optimized by density functional theory (DFT) at the B3LYP/6–311+G(d,p) level and the theoretical and experimentally obtained parameters were compared. The frontier molecular orbitals HOMO and LUMO were generated, giving an energy gap ΔE of 4.0931 eV. The MEP was generated to identify active sites in the molecule and molecular docking studies carried out with the title compound (ligand) and the covid-19 main protease PDB ID: 6LU7, revealing a moderate binding affinity of −5.4 kcal mol−1.

Keywords

• crystal structure
• hirshfeld surface
• dft studies
• molecular docking
• isonicotinate