Exploring host-guest interactions of sulfobutylether-β-cyclodextrin and phenolic acids by chemiluminescence and...

We have developed a rapid method that allows us to characterize the binding interaction of sulfobutylether-β-cyclodextrin (SBE-β-CD) with five therapeutically important phenolic acids: ferulic acid, caffeic acid, gallic acid, protocatechuic acid, and vanillic acid. The method utilizes a flow-injection chemiluminescence (FI-CL) technique that relies on the inhibition of a cyclodextrin-luminol chemiluminescence (CL) by increasing amounts of the phenolic acids (PAs). This loss of CL with increasing amounts of PAs fits the equation lg[(I0-Is)/Is]=lgKPAs+nlg[PAs], allowing calculation of the binding constant (KPAs) and stoichiometric ratio (n). The five phenolic acids and SBE-β-CD formed complexes with a stoichiometric ratio of 1:1. The binding constants were on the order of 10(7) M(-1). These results showed a good correlation with the scores calculated by molecular docking. Further investigation by site-directed molecular docking and linear correlation analysis revealed that PAs entered the larger cavity of SBE-β-CD and the formation constants mainly depended on the number of hydrogen bond acceptors in the PAs structures. All these results indicate that the CL-based affinity method can be used for direct determination of host-guest inclusion interactions and has great potential to become a reliable alternative for quantitatively studying host-guest binding and drug-protein interactions.