Stereoselective interaction of cinchona alkaloid isomers with bovine serum albumin

• The binding discrepancy of QN and QD towards BSA was investigated.
• The absolute configuration of stereoisomers affects the ligand–protein interaction.
• The binding affinity of QN to BSA is stronger than that of QD.
• QD exhibits lower efficiency in quenching BSA emission as compared to QN.
• BSA recognized QN and QD with unequal spectral response and structural perturbation.

The dependence of the interaction between bovine serum albumin (BSA) and two cinchona alkaloids, quinine (QN) and quinidine (QD), on the absolute configuration of these stereoisomers has been comprehensively studied. The FTIR spectra showed that QN and QD interacted with both CO and C–N groups of BSA, resulting in changes to the secondary structure of the protein. Fluorescence quenching of BSA by the stereoisomers revealed lower efficiency for QD in quenching the Trp emission of BSA when compared to QN. Further analysis accurately described the different binding behaviors and recognition discrepancies of QN and QD towards BSA, which was reflected through binding affinities, driving forces, energy changes and conformational changes during the ligand–protein interactions. Synchronous fluorescence further proved that QD was farther from Trp and Tyr than that of QN. This work could provide basic data for clarifying the binding interaction, metabolism and distribution of cinchona alkaloid stereoisomers in vivo.