DFT and Molecular Docking Analysis of Newly Synthesized
Compound (2E)-3-[3-(Benzyloxy) Phenyl]-1-(4’-Chlorophe-Nyl)-
2-Propen-1-One [Bpclpo]
Authors: Anbukarasi Karunanithi , Xavier Susaimarie , Hasan Aso Hameed , Er Yeap Lon , Jamalis Joazaizulfazli , Sebastian Simon , Periandy Sengeny 
Published: September 2022

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.

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.

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 the auto dock 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 electrondeficient
centres were investigated. The electronic spectra of λmax 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 de-shielded in NMR, resulting in stronger
fields and chemical shifts. The Harmonic Oscillator Model of Aromaticity (HOMA)and the retain
ability of aromaticity in the addition and removal of electrons are 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) (π→π*)
due to phenyl transition belonging to Cl atom in the ring. In the solvent phase, UV-visible spectra reveal
a prominent peak at 300 λmax, with an absorbance range of intensity of 0.6983. (a.u.). According
to TG/DSC experiments, the molecule begins to break around 290-370°C, and total decomposition
occurs at 300°C. 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.