Thiophene and sulfonamide derivatives serve as biologically active compounds, used for the manufacture of large numbers of new drugs. In this study, 11 selected derivatives of thiophene sulfonamide were computed for their geometric parameters, such as hyperpolarizability, chemical hardness (ƞ), electronic chemical potential (μ), electrophilicity index (ω), ionization potential (I), and electron affinity (A). In addition, FT-IR and UV-Vis spectra were also simulated through theoretical calculations. The geometrical parameters and vibrational frequencies with assignments of the vibrational spectra strongly resemble the experimentally calculated values. Besides, the frontier molecular orbitals were also determined for various intramolecular interactions that are responsible for the stability of the compounds. The isodensity surfaces of the frontier molecular orbitals (FMOs) are the same pattern in most of the compounds, but in some compounds are disturbed due to the presence of highly electronegative hetero-atoms. In this series of compounds, 3 shows the highest HOMO–LUMO energy gap and lowest hyperpolarizability, which leads to the most stable compound and less response to nonlinear optical (NLO), while 7 shows the lowest HOMO–LUMO energy gap and highest hyperpolarizability, which leads to a less stable compound and a high NLO response. All compounds have their extended three-dimensional p-electronic delocalization which plays an important role in studying NLO responses.

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.

In the present study, pyrazole-thiophene-based amide derivatives were synthesized by different methodologies. Here, 5-Bromothiophene carboxylic acid (2) was reacted with substituted, unsubstituted, and protected pyrazole to synthesize the amide. It was observed that unsubstituted amide (5-bromo-N-(5-methyl-1H-pyrazol-3-yl)thiophene-2-carboxamide (7) was obtained at a good yield of about 68 percent. The unsubstituted amide (7) was arylated through Pd (0)-catalyzed Suzuki–Miyaura cross-coupling, in the presence of tripotassium phosphate (K₃PO₄) as a base, and with 1,4-dioxane as a solvent. Moderate to good yields (66–81%) of newly synthesized derivatives were obtained. The geometry of the synthesized compounds (9a–9h) and other physical properties, like non-linear optical (NLO) properties, nuclear magnetic resonance (NMR), and other chemical reactivity descriptors, including the chemical hardness, electronic chemical potential, ionization potential, electron affinity, and electrophilicity index have also been calculated for the synthesized compounds. In this study, DFT calculations have been used to investigate the electronic structure of the synthesized compounds and to compute their NMR data. It was also observed that the computed NMR data manifested significant agreement with the experimental NMR results. Furthermore, compound (9f) exhibits a better non-linear optical response compared to all other compounds in the series. Based on frontier molecular orbital (FMO) analysis and the reactivity descriptors, compounds (9c) and (9h) were predicted to be the most chemically reactive, while (9d) was estimated to be the most stable among the examined series of compounds.

Synthesis of 5-aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides (4a–4n) by a Suzuki cross-coupling reaction of 5-bromo-N-(pyrazin-2-yl)thiophene-2-carboxamide (3) with various aryl/heteroaryl boronic acids/pinacol esters was observed in this article. The intermediate compound 3 was prepared by condensation of pyrazin-2-amine (1) with 5-bromothiophene-2-carboxylic acid (2) mediated by TiCl₄. The target pyrazine analogs (4a–4n) were confirmed by NMR and mass spectrometry. In DFT calculation of target molecules, several reactivity parameters like FMOs (E_HOMO, E_LUMO), HOMO–LUMO energy gap, electron affinity (A), ionization energy (I), electrophilicity index (ω), chemical softness (σ) and chemical hardness (η) were considered and discussed. Effect of various substituents was observed on values of the HOMO–LUMO energy gap and hyperpolarizability. The p-electronic delocalization extended over pyrazine, benzene and thiophene was examined in studying the NLO behavior. The chemical shifts of ¹H NMR of all the synthesized compounds 4a–4n were calculated and compared with the experimental values.

In this work, we described the synthesis of 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate by reacting 5-bromofuroic acid with methylparaben in the incorporation of DCC/DMAP (Steglich esterification) as coupling agents. Later on, we subsequently synthesized a series of 4-(methoxycarbonyl)phenyl 5-aryl furan-2-carboxylates (5a–5e) through Suzuki coupling catalyzed by palladium (0) between 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate (3) with several substituted arylated and heteroaryl boronic acids (4). DFT calculations were computed to elucidate electronic structural features of synthesized molecules (5a–5e) and to validate these findings by correlating with theoretical and experimental spectroscopic analysis. Furthermore, geometrical optimization, thermodynamic features, as FMO orbitals, MESP maps, NLO behavior and reactivity descriptors, were also determined from the PBE0 D3BJ/def2-TZVP/SMD_1,4-dioxane theory level to confirm the structural features of synthesized molecules.