Synthesis and Computational Analysis of Novel Carboximidamide/ Benzothiazole and 1,2,4-Oxadiazole/Benzothiazole Hybrid Compounds for Biological Applications

A new series of N'-[2-(1,3-benzothiazol-2-ylthio)acetoxy]aryl-2-carboximidamides (5a-5i) and 2-([(3-aryl-1,2,4-oxadiazol-5-yl)methyl]thio)-1,3-benzothiazoles (6a-6i) were successfully synthesized in good to excellent yields by reacting (1,3-benzothiazol-2-ylthio)acetic acid (2) with the respective arylamidoximes (4a-4i). The reactions were carried out in dry polar aprotic solvents, with acetonitrile used for the synthesis of 5a-5i and dimethylformamide for 6a-6i, in the presence of N,N'-carbonyldiimidazole as a coupling reagent. The structures of the target synthesized were clearly confirmed through IR, NMR, elemental analysis, and mass spectrometry data. The electronic properties and optimized geometries of compounds 5a–6i, analyzed through DFT (Density Functional Theory), provided valuable insights into their reactivity and interaction potential with biological targets. Analysis of the HOMO and LUMO highlighted regions of nucleophilic and electrophilic interactions, which are influenced by the presence of electron-donating and withdrawing substituents. These electronic factors correlate directly with the predicted biological activities of the compounds. Notably, compounds 5 g and 6 g emerged as the most promising candidates for biological applications, displaying narrow energy gaps, high electrophilicity indices, and balanced chemical hardness, indicating the importance of tuning electronic properties to optimize biological efficacy.