Experimental and Theoretical Studies of Pyrazole-4 Derivatives by X-Ray Crystallography, DFT, Molecular Docking, and Molecular Dynamics Simulation

Abstract

Nitrogen-containing heterocycles play a crucial role in drug design and discovery. Pyrazole derivatives have garnered attention due to their unique and intriguing features. This study investigates the structure and properties of two pyrazole-4-carbaldehyde derivatives (3 and 4). We report the single crystal structure of one of the intermediate compounds, 1-(1-(4-bromophenyl)ethylidene)-2-(2-chlorophenyl)hydrazine (2), and a final compound, 1-(2-chlorophenyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (3). We analysed the non-covalent interactions within the crystal using Hirshfeld surface analysis and 2D fingerprint plots. We also used density functional theory (DFT) at the B3LYP/6-311G(d,p) level to optimise the structures and understand electronic properties, transitions and vibrational frequencies. To predict the anti-inflammatory potentials and selectivity of 3 and 4, molecular docking and molecular dynamics (MD) simulation studies against COX1 (PDB ID: 1EQG) and COX2 (PDB ID: 1CX2) receptors were conducted. Overall, this study sheds light on the structural, chemical, and biochemical features of two pyrazole-4-carbaldehyde derivatives.