Computational Study of Benzothiazole Derivatives for Conformational, Thermodynamic and Spectroscopic Features and Their Potential to Act as Antibacterials

Abstract

Benzothiazole analogs are very interesting due to their potential activity against several infections. In this research, five benzothiazole derivatives were studied using density functional theory calculations. The optimized geometry, geometrical parameters and vibrational spectra were analyzed. The charge distribution diagrams, such as FMO (HOMO-LUMO), energies of HOMO-LUMO, polarizability, hyperpolarizability, MESP and density of states, were calculated. The computed energies of HOMO and LUMO showed that the transfer of charge occurred within the compound. The effect of the change of substituents on the ring on the value of the HOMO-LUMO energy gap was also observed. It was observed that, in this series, compound 4 with CF3 substituent had the lowest energy gap of HOMO-LUMO, and compound 5 with no substituent had highest HOMO-LUMO energy gap. From the energies of HOMO and LUMO, the reactivity descriptors, such as electron affinity (A), ionization potential (I), chemical softness (σ), chemical hardness (ƞ), electronic chemical potential (μ), electrophilicity index (ω), were calculated. In addition, the 13C and 1H NMR chemical shifts of the molecules were calculated using the gauge-independent atomic orbit (GIAO) method; the shifts were in good agreement with the experimental values. The anti-bacterial potential of compounds 1 to 5 was tested by molecular docking studies toward target proteins 2KAU and 7EL1 from Klebsiella aerogenes and Staphylococcus aureus. Compounds 3 and 1 showed high affinity toward 2KAU and 7EL1, respectively.

Keywords

• density functional theory
• conformational analysis
• benzothiazole
• hyperpolarizability
• molecular docking