Kinetics and thermodynamics of berberine inclusion in cucurbit[7]uril.

The kinetics and thermodynamics of berberine inclusion in cucurbit[7]uril was studied by stopped-flow method, fluorescence titrations, and isothermal calorimetry in neat water. The ~500-fold fluorescence intensity enhancement upon encapsulation was exploited to monitor the complex formation in real time at various temperatures. The increase in the fluorescence intensity could be fitted well by assuming a simple 1:1 binding equilibrium without any intermediate formation. For the rate constants of association and dissociation, (1.9 ± 0.1) × 10(7) M(-1) s(-1) and (0.81 ± 0.08) s(-1) were found at 298 K, respectively. The ingression into the cavity of CB7 had 32 ± 2 kJ mol(-1) activation enthalpy, implying a constrictive binding, whereas 69 ± 2 kJ mol(-1) was obtained for the activation enthalpy of the egression. Substantial structural change had to occur when berberine passed through the tight carbonyl-rimmed portal of the macrocycle to reach the transition state. An enthalpy-driven complexation took place with a slight entropy gain.