Cooperative binding of an anticancer drug in a guest–host–protein assembly

Abstract

The supramolecular formation of an anticancer drug (6-mercaptopurine (6-MP)) in an acetate buffer solution was demonstrated through a host–guest interaction with the macrocyclic host cucurbit[7]uril (Q[7]) and bovine serum albumin (BSA). With the help of ultraviolet absorption and fluorescence spectroscopy, it was shown that a binary complex formed between 6-MP and Q[7] and/or BSA, and a specific binding interaction took place between 6-MP and Q[7] in the presence of BSA. The inclusion constants and thermodynamic parameters were determined at different temperatures. The data suggested that the formation of the binary 6-MP–Q[7] complex was driven by enthalpy in the presence of an unfavourable entropy, which was attributed to the van der Waals and hydrophobic interactions. The fluorescence quenching of BSA by 6-MP was a result of the formation of the 6-MP–BSA complex. This quenching occurred by a static quenching mechanism, and hydrophobic forces played predominant roles in the binding process. Moreover, the absorption data suggested that the interaction between 6-MP and Q[7] or BSA was a competitive process. In addition, the effect of 6-MP on BSA conformation was investigated by synchronous and 3D fluorescence spectra.