Synthesis of thiophene derivatives: Substituent effect, antioxidant activity, cyclic voltammetry, molecular docking, DFT, and TD-DFT calculations

The efficient pathway 6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate derivatives have been synthesized. Due to the promising biochemical reactivity, the bioactive agent synthesis in the frame of the thiophene moiety is one of the main objectives of the contemporary scientific disciplines. The structures of all the presently synthesized compounds were confirmed using spectroscopic methods (UV-vis, FT-IR, H-1 NMR, C-13 NMR). The cyclic voltammetry (CV) of three compounds (1-3) was performed using a bare ITO electrode and a Nafion modified ITO (Indium Tin Oxide) electrode. The antioxidant properties of these compounds were explored by the CUPRAC method and TEAC (Trolox equivalent total antioxidant capacity) coefficients revealed that the antioxidant capacity of the compounds was ranking as follows: compound 2 (C-2) > compound 3 (C-3) > compound 1 (C-1). The docking studies displayed that compound 1 was the most active compound against Escherichia coli thymidylate synthase (TS). The TD-DFT calculations displayed that two observed peaks on the UV-vis spectra of the thiophenes were related to the n & nbsp;-> pi* and pi & nbsp;-> pi* transitions. Also, NBO (Natural Bond Orbital) analysis indicated that the resonance interactions (n & nbsp;-> pi* and pi & nbsp;-> pi*) in the ground state of all compounds had an essential role in the decreasing of the stabilization energy. The antioxidant activity and molecular docking results were supported by the electrodonating power and hardness indexes in addition to the NBO results. (C)& nbsp;2022 Elsevier B.V. All rights reserved.

Automated summary

Efficient pathway synthesis of 6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate derivatives was achieved. The structures of the synthesized compounds were confirmed using spectroscopic methods. Antioxidant assays revealed that compound 2 exhibited the highest antioxidant capacity, followed by compound 1 and compound 3. Docking studies demonstrated that compound 1 had the strongest inhibitory activity against Escherichia coli thymidylate synthase. TD-DFT calculations and NBO analysis further supported the conclusions drawn from the antioxidant assays and docking studies.