ABSTRACT
CONTEXT: The present work encompasses the theoretical investigation of 14 benzimidazole-based (seven vinyl fused monomeric benzimidazole (VFMBI) and seven vinyl fused oligomeric benzimidazole (VFOBI)) derivatives using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) techniques. The effects of electron donor and acceptor groups on the electronic structure such as HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energies, HOMO-LUMO energy gap, ionization potentials (IPs), electron affinities (EAs), internal reorganization energies of holes and electrons (λh/e), and excited state properties have been explored in the present work. In addition, natural bond orbital (NBO) analysis of these compounds has been investigated to reveal the typical stabilization interactions in these molecules. Hence, the aim of the present work is to explore the electronic structures and optoelectronic properties of the title molecules on the basis of the DFT quantum chemical calculations and to make an idea on the parameters influencing the optoelectronic efficiency toward a better understanding of the structure-property relationships. Moreover, the calculated results reveal the suitable optoelectronic properties of benzimidazole oligomer derivatives using theoretical techniques. Of the investigated molecules, 4_MABIMCY and 4_MABIOCY show potential optoelectronic properties and can be used as a potential charge transport material due to their narrow band gap, high hyperpolarizability, low ionization potential, and high electron affinity. The larger λab and λem values favor the system to be used as a potential optoelectronic material with better optical properties. METHODS: All quantum chemical calculations were carried out using Gaussian09 theoretical chemistry code. Ground state calculations were made using the B3LYP/6-31+G(d,p) method. All excited state calculations had been computed using TDB3P86/6-311++(d,p). The initial structure for excited state calculations was optimized using the AM1 semi-empirical method.
ABSTRACT
In this paper, two series of novel multifunctional 1, 4-di (aryl/heteroaryl) substituted piperazine derivatives (6a-d & 7a-d) were synthesized, characterized, and evaluated for their antitubercular, antibacterial, and antifungal activities. A step-wise reduction, bromination and substitution reactions on various aldehydes resulted in alcohols (2a-d), bromides (3a-d), and titled novel compounds (6a-d & 7a-d) in moderate to good yields (48-85%). The novel compounds were evaluated for their antitubercular and antimicrobial activities. Compound 7a exhibited promising antitubercular activity (MIC: 0.65 µg/mL) almost equal to the Rifampicin, while the rest of the compounds were moderately active against MTB H37Rv except 6b. Compounds 7a and 6b showed good activity against tested fungal pathogens. Compounds 7a and 7b were proven as the best bacterial agents. Molecular docking studies were in agreement with the in-vitro results. Docking analyses show that all the synthesized molecules bind to the target protein Mtb RNAP (PDB ID: 5UHC) fairly strongly. All the compounds were evaluated for their in vitro cytotoxicity effect using the MTT assay method against human cancer cell line MCF-7. The compounds demonstrated growth inhibitory effect on the cell line with significant IC50 values ranging between 8.20 and 34.45 µM. Most importantly, compound 7a displayed good binding affinity towards the tested protein with binding energy -7.30 kcal/mol and a stronger hydrogen bond distance of 2.2 Å with ASN-493 residue. Thus, the present research highlighted the potential role of novel piperazine derivatives as potential antitubercular, and antimicrobial candidates and further good research into optimization might result in the development of new antitubercular drug candidates.
