Abstract
•Synthesis of novel thiazolyl-thiophene hybrids and elucidation of their chemical structures.•DFT/B3LYP studies were applied to explore the structural and electronic properties.•The thiazolyl-thiophene hybrids displayed rational antioxidant activity (DPPH assay).•Molecular docking assessments (PDB Code- 3OXI) were utilized to explore the binding affinity.
The targeted N-(thiazol-2-yl)thiophene-2-carboxamide derivatives 4–9 were synthesized based on heterocyclization of the functionalized thiocarbamoyl precursors 1 and 2 with 2-chloroacetamido-thiazole (3). The synthesized compounds were studied using DFT/B3LYP level to explore their structural and electronic properties. The frontier molecular orbital, HOMO and LUMO, showed that HOMO was consisted mainly of heteroatoms non-bonding lone pairs of electrons and the π-orbitals of the phenyl and thiophene rings with minor contribution from the thiazole nucleus of the non-bonding lone pairs. Furthermore, the investigated compounds had low energy gap (ΔEH-L), 1.64–2.62 eV, with the derivatives 7 and 4 having lowest and highest gap, respectively. The synthesized compounds exhibited good NLO properties due to their lower charge transfer resistance. The antioxidant activity for the synthesized thiazolyl-thiophene hybrids showed rational antioxidant effectiveness over DPPH technique. The results showed that hybrids 5, 7 and 9 exhibited respectable antioxidant with IC50 values (32.26±0.07, 27.31±0.23 and 23.17±0.36), respectively. However, thiazolyl-thiophene hybrids 4, 6 and 8 were shown tolerable IC50 values (43.28±0.14, 35.36±0.11 and 37.52±0.04), respectively against both of BHT (Butylated hydroxytoluene) and Ascorbic acid as references. The molecular docking estimation was also used on the generated thiazolyl-thiophene hybrids (PDB Code- 3OXI). The hybrids 4, 6 and 8 demonstrated a high binding affinity for the 3OXI amino acids. The docking results were satisfactory, and they mirrored the findings of the antioxidant study.
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