Interactions of cucurbit[6,7]urils with human serum albumin and their effects on zaltoprofen transportation†
Abstract
Cucurbit[6,7]urils (CB[6,7]s) have been extensively investigated because of their characteristic inclusion ability. To enhance our understanding of the behaviors of CB[6,7]s in biological environments and explore their effects on drug transportation, multi-spectroscopic and molecular docking methods were applied to examine the binding mechanism of CB[6,7]s with human serum albumin (HSA) and their interference on the HSA–zaltoprofen (ZPF) binding system. 1H NMR spectra revealed the complexes that formed between CB[6,7]s and HSA, as well as between ZPF and HSA. The fluorescence of HSA was quenched by ZPF through a combined static and dynamic mechanism. The added CB[6,7]s did not significantly affect the energy transfer efficiency, but decreased the HSA–ZPF binding constant. The binding stoichiometry of ZPF with HSA was 1 : 1, and this value remained unchanged when CB[6,7]s were added. Circular dichroism spectroscopy, synchronous and 3D fluorescence spectroscopy demonstrated that CB[6,7]s slightly influenced the native secondary structure of HSA and its ZPF-induced unfolding. Further molecular docking suggested that CB[6,7]s preferred to bind to the HSA surface, and ZPF was primarily located in an L-shaped cavity in subdomain IB. Therefore, CB[6,7]s elicited minor damage to the structure of HSA and weak interferance with drug transportation.