Synthesis and spectral characterization of 4-methylthiazole derivatives: DFT approach and biological activities

Abstract

The design of organic molecules as drug molecules holds tremendous promise for success in both the present and future. Among the various types of compounds, heterocyclic compounds play a crucial role as they are extensively found in nature and are vital for life's processes. Their widespread presence and importance make them invaluable in the field of drug discovery and development. In this study, we present a thorough examination of 4-methylthiazole compounds (MTs) that are synthesized using a simple, straightforward protocol. Our analysis aims to provide a comprehensive understanding of these compounds. Various techniques, including proton and carbon NMR, mass spectrometry, FT-IR, and UV spectroscopy, are employed to perform an in-depth characterization of the MTs. The molecular structures of the synthesized substances, namely 6, 7, and 9, are investigated using density functional theory (DFT) with 6-311++G(d,p) as the basis set. By utilizing the DFT/B3LYP technique, the polarizability (α₀) and first hyperpolarizability (β₀) values are determined. Notably, the computed results for β₀ suggested the potential presence of non-linear optical (NLO) behavior in all the molecules. Furthermore, the energies of the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), and the molecular electrostatic potential (MEP) are calculated and thoroughly examined to gain insights into the reactive sites of the molecules. The MEP surface is used to comprehend the locations of reactivity within the molecule. Additionally, the Mulliken atomic charges of carbon, oxygen, and nitrogen atoms are calculated using the same basis set. The anti-inflammatory and anti-diabetic properties of MTs are evaluated using protein denaturation and α-amylase inhibitory methods, respectively. Remarkably, the MTs demonstrated greater effectiveness compared to the standard drugs diclofenac and acarbose, respectively, indicating their potential as potent therapeutics for inflammation and diabetes treatment.