An MEDT study of Diels-Alder reactions of a tetrahydroazulenone with maleimides: Mechanism, selectivity, and antimicrobial insights

The Diels-Alder cycloaddition of cyclopentadienone derivative 3-methyl-5,6,7,8-tetrahydroazulen-1(4H)-one with a series of maleimide derivatives is studied using Molecular Electron Density Theory at the B3LYP/6-311++G(d,p) computational level. Conceptual Density Functional Theory analysis predicts low reaction polarity, which is confirmed by global electron density transfer analysis at the transition structures. Topological analysis reveals the electron distribution and evolution of multiple covalent and non-covalent interactions at the transition structures. The results indicate that these Diels-Alder reactions follow an asynchronous one-step mechanism under kinetic control, favouring the endo product formation. Bonding Evolution Theory shows that the reaction mechanism can further be decomposed into five distinct bonding evolution phases. In addition, a molecular docking study is conducted to assess the antimicrobial potential of the reaction products against Escherichia coli and Staphylococcus aureus. An evaluation of the results of binding affinity and molecular interactions concludes that the products are viable as antimicrobial agents.