Microwave-Assisted Synthesis and Characterization of Some Aldehyde Derivatives of Imidazo[2,1-b][1,3,4]thiadiazole: Crystal Structure Insights, In-Silico and Biological Studies

The microwave-assisted synthesis, crystallographic studies, in-silico docking and the evaluation of in-vitro biological activities of 2-(3,4-dimethoxy)-6-(substituted phenyl)- imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehydes is represented here. Single-crystal X-ray diffraction experiments were used to identify the crystal structure of the 6-(4-chlorophenyl)-2-(3,4-dimethoxybenzyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde. Using fingerprint plots, Hirshfeld surface analysis was used to confirm the contributions of distinct intermolecular interactions in the development of the crystal packing. Further, density functional theory calculations were employed to calculate the molecule's electronic properties. The chemically active regions on the molecule are identified by analysing the molecular electrostatic potential map. in-silico studies revealed that the molecules can be effectively used as antibacterial agents by taking the 3q82 receptor with chloramphenicol as a standard. As compared to the chloramphenicol standard, in-vitro tests showed that molecules 4 a, 4 b, 4 c, and 4 f had a zone of inhibition that ranged from 9 to 11 mm against both Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria. The minimum inhibitory concentration was between 40 to 70 mu g/ml. These compounds ' Hydroxyl free radical scavenging activity was between 40 to 85 %. Whereas, DPPH radical scavenging activity was between 40 and 70 %. Percentage hemolysis or cell protective activity of the compounds was ineffective at 20-40 %. The advantages of microwave heating are reduced reaction time, increased product formation, ease of handling, and lesser byproducts. Structure validation, electrical properties and surface characteristics were done using single crystal XRD, DFT and Hirshfeld Surface Analysis respectively. Biological examination of the synthesized compounds supported the in-silico docking studies.image