DFT and molecular docking analysis of newly synthesized compound (2E)-3-[3-(benzyloxy) phenyl]-1-(4’-chlorophenyl)-2-propen-1-one [BPClPO]

Abstract

Aims To synthesise (2E)-3-[3-(benzyloxy) phenyl]-1-(4’-chlorophenyl)-2-propen-1-one [BPClPO] and perform DFT and molecular docking analysis of the synthesized compound to better understand its medicinal properties. Background The parent molecule in the skeleton of this chalcone is the benzyloxy phenyl, which is linked to the chlorophenylpropen at C-3. The hydrophobic phenyl groups are naturally resistant to oxidation and reduction. Antiviral, antimalarial, antibacterial, anti-inflammatory, anticancer, antioxidant, antitubercular, and anti-Alzheimer activities are among the many pharmacological properties of chalcone derivatives. As a result, chalcone-based compounds are investigated using molecular docking and molecular modelling calculations to determine their suitability for drug formulation. Objective The characterization of BPClPO is investigated in this study using various approaches, including wavefunction analysis and spectral analysis, which are associated with quantum chemical calculations to investigate its medicinal properties. Methods The Gaussian 09W programme was used to perform computational chemistry calculations. The BPClPO's molecular structure was optimised, and the vibrational frequencies, Natural Bond Orbital (NBO), Fukui function, electronic properties and Nuclear Magnetic Resonance (NMR) chemical shifts were calculated using the B3LYP/6-311G (d, p) as the basis set. The VMD user interface and Multiwfn (3.4.1) software were used to conduct topological analyses of the Electron Localization Function (ELF), Localized Orbital Locator (LOL) and Reduced Density Gradient (RDG). The binding sites of active cancer proteins were calculated using autodock and auto grid. Results Theoretical reaction path investigation was done for BPClPO to detect reactions from the parent chemical to the synthesized compound. Theoretical bond lengths and bond angles are compared with XRD values. Theoretical values of vibrations caused by electron-rich and electron-deficient centres were investigated. The electronic spectra of ?max were examined under UV-Vis light and the electron absorbance spectrum was absorbance wavelength and oscillator strength compared to theoretical values. The electron-rich carbon atoms are deshielded in NMR, resulting in stronger fields and chemical shifts. The Harmonic Oscillator Model of Aromaticity (HOMA) retainability of aromaticity in the addition and removal of electrons is examined in the Nucleus Independent Chemical Shift (NICS) study. The stability of the compound was investigated using Thermo-Gravimetric analysis and Differential Scanning Calorimeter (TG/DSC) analysis. Four cancer proteins with the reactive site were studied in docking simulations. Conclusions The NBO analysis determined the intramolecular charge transfer within the molecule of high stabilization transition from C34-C37 donor to C35-C39 acceptor of (22.31 Kcal/mol) (???*) due to phenyl transition belonging to Cl atom in the ring. In the solvent phase, UV-visible spectra reveal a prominent peak at 300 ?max, with an absorbance range of intensity of 0.6983. (a.u.). According to TG/DSC experiments, the molecule begins to break around 290-3700C, and total decomposition occurs at 3000C. The molecule was found to have a higher bioactivity than and was employed related more to medicinal properties mechanism(s) of action in drug docking investigations.