Induced chirality in fisetin upon binding to serum albumin: experimental circular dichroism and TDDFT calculations.

Theoretical absorption and electronic circular dichroism (ECD) spectra predicted via time-dependent density functional theory (TDDFT) calculations on the neutral and four anionic species of fisetin, an achiral flavonoid, were used to rationalize the experimental absorption and induced circular dichroism (ICD) spectra of the ligand upon binding to human serum albumin (HSA). On this basis, the mechanism responsible for the appearance of the ICD signal was ascribed to a distortion of the conformation of bound fisetin. Furthermore, comparison of the simulated and experimental spectra revealed that two fisetin species bind to HSA, namely, the neutral molecule and the anion deprotonated at the hydroxyl group in position 7, in a 1:1 ratio. The coupling of the theoretical results with the experimental absorption and ICD data allows identification of the flavonoid species that bind to the protein and evaluation of their conformation in the binding site.