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

Theoretical and experimental structural studies of the title compound were undertaken using X-ray and DFT methods. The inter­actions present in the crystal were analyzed using Hirshfeld surface and MEP surface analysis. Docking studies with a covid-19 main protease (PDB ID: 6LU7) as the target receptor indicate that the synthesized compound may be a potential candidate for pharmaceutical applications.

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 E_ele = 59.2 kJ mol⁻¹, E_pol = 15.5 kJ mol⁻¹, E_dis = 140.3 kJ mol⁻¹ and E_rep = 107.2 kJ mol⁻¹ with a total inter­action energy E_tot 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.