Inclusion complex formation of sanguinarinealkaloid with cucurbit[7]uril: inhibition of nucleophilic attack and photooxidation

Abstract

The inclusion of sanguinarine, a biologically active natural benzophenanthridine alkaloid, in cucurbit[7]uril (CB7) was studied by NMR and ground-state absorption spectroscopy, as well as steady-state and time-resolved fluorescence measurements in aqueous solution. The iminium form of sanguinarine (SA⁺) produces very stable 1 : 1 inclusion complex with CB7 (K = 1.0 × 10⁶ M⁻¹), whereas the equilibrium constant for the binding of the second CB7 is about 3 orders of magnitude smaller. Marked fluorescence quantum yield and fluorescence lifetime enhancements are found upon encapsulation of SA⁺ due to the deceleration of the radiationless deactivation from the single-excited state, but the fluorescent properties of 1 : 1 and 1 : 2 complexes barely differ. The equilibrium between the iminium and alkanolamine forms is shifted 3.69 pK unit upon addition of CB7 as a consequence of the preferential encapsulation of the iminium form and the protection of the 6 position of sanguinarine against the nucleophilic attack by hydroxide anion. On the basis of thermodynamic cycle, about 225 M⁻¹ is estimated for the equilibrium constant of the complexation between the alkanolamine form of sanguinarine (SAOH) and CB7. The confinement in the CB7 macrocycle can be used to impede the nucleophilic addition of OH⁻ to SA⁺ and to hinder the photooxidation of SAOH.