LAUSR

Abstract Crown ethers are kinds of macrocyclic compounds with high selectivity to metal cations, which can be used as ion sensors, ion analytical reagents and ionophores for biological applications. The chemical reactivity of 1,8-dihydroxyl-4,4,5,5-tetramethylbenzo-14-crown-4 had been investigated at the level of M062X/def2TZVP with Gauss16. The conformations were studied though the high-temperature annealing process with Gromacs. The applicability of Frontier molecular orbital theory, Conceptual density functional theory and Molecular electrostatic potential analysis for the reactivity prediction were discussed. The analysis results show that the methods reflecting the electronic softness property such as Fukui function, global softness, relative nucleophilicity, are suitable for the prediction of electrophilic substitution reaction sites. The electrophilic substitution reaction sites of different conformations are at the C25 or C26 atom, which has the largest HOMO orbital compositions. The oxygen atoms of the main ring and the hydroxyl groups are the binding sites of metal cations. The lowest electrostatic potential is −74.81 kcal/mol on the vdW surface of (1R, 8S) 1,8-dihydroxyl-4,4,5,5-tetramethylbenzo-14-crown-4 contributing to the lone pair electrons and π-electron cloud. The hydroxyl groups and the benzene ring can decrease the surface potential and increase the reactivity.