Bioactive Small Molecule, Piperazinium Bis(4-Hydroxybenzenesulphonate) upon Spectral Investigation, Hirshfeld Surface Analysis, Molecular Docking and ADMET Prediction: A Complement DFT Calculations

Abstract

Piperazinium bis (4-hydroxybenzenesulphonate) (P4HBS) was studied using FT-IR, FT-Raman, UV spectra, and quantum chemical calculations. To obtain the geometry of the molecule, computational methods were used with the Gaussian’09w package and B3LYP/cc-pVTZ as the basis set. The stretching wave number of hydrogen bond donor NH₂⁺ and hydrogen bond acceptor SO₃⁻ is red shifted due to protonation, according to vibrational analysis. Frontier molecular orbital analysis was used to confirm the molecule’s molecular reactivity and kinetic stability. The electronic transition observed in the UV-visible spectrum, which was measured experimentally, was identified using TD-DFT. MEP plot, Fukui function. Natural population analysis confirm that OH groups and SO₃ groups are electrophilic attack sites, while hydrogen atoms in the Piperazinium ring are nucleophilic attack sites. The Independent Gradient Model (IGM) and Hirshfeld surface analysis were used to determine the weak van der Waals and strong intermolecular hydrogen bonding interactions, respectively. The antifungal activity against the fungus Candida albicans and Aspergillus flaves was determined by the disk diffusion technique. Through binding energy, molecular docking studies were performed to identify the effective lead compound against the C. albicans fungal pathogen. ADMET properties with improved pharmacokinetic properties were predicted.

Keywords:

• Charge transfer
• charge transfer excitation
• singly occupied molecular orbital
• spin density
• independent gradient model

Acknowledgements

The Authors thank Dr. I. Hubert Joe, Associate Professor of Department of Physics, Kerala University for granting us permission to do computational works in their Research Lab.

Disclosure statement

No potential conflict of interest was reported by the author(s).