Role of kinetic stabilization in the inclusion of the pharmaceutically important chelerythrine and nitidine alkaloids in cucurbit[7]uril

Abstract

The inclusion of chelerythrine and nitidine quaternary benzo[c]phenanthridine plant alkaloids in cucurbit[7]uril (CB7) was studied by stopped-flow method, isothermal calorimetry, spectrophotometric and fluorescence titrations in aqueous solution at pH 4. The molecular structure of the guests differed only in the position of a methoxy group linked to the isoquinoline moiety. Despite the minor alteration in the substitution pattern, fundamentally dissimilar kinetic and thermodynamic characteristics were found for the two alkaloids. Nitidine encapsulation in CB7 was kinetically stabilized because the activation enthalpy significantly exceeded the exothermicity of the binding. In contrast, chelerytrine-CB7 complex formation had slightly lower energy barrier and the ∼ 20 kJ mol−1 larger enthalpy gain significantly contributed to the driving force of association. The rates of exit from CB7 differed to a small extent for the two alkaloids because the effect of the lower activation enthalpy of nitidine egression was almost compensated by the unfavourable activation entropy of the process.