Elucidation of the intermolecular interactions of human serum albumin with pyrene and its derivatives: The effects of substituents

The intermolecular interactions between pyrene (Pyr) or its derivatives with different types of substituents (i.e., 1-hydroxypyrene (HPyr), 1-nitropyrene (NPyr), 1-aminopyrene (APyr), and 1-methylpyrene (MPyr)) and human serum albumin (HSA) were explored by multispectroscopy combined with molecular docking. Fluorescence spectral analysis showed that Pyr and its derivatives quenched the fluorescence of HSA mainly through the static mechanism and could form 1:1 complexes with HSA in the growing affinity order of Pyr (0.26 × 10 5 L mol −1 ), APyr (0.33 × 10 5 L mol −1 ), HPyr (1.23 × 10 5 L mol −1 ), NPyr (2.53 × 10 5 L mol −1 ) and MPyr (12.49 × 10 5 L mol −1 ) at 298 K. Molecular docking indicated that hydrophobic and π-stacking interactions were formed between Pyr/HPyr/NPyr/APyr/MPyr and its surrounding amino acid residues in the IB subdomain of HSA, while hydrogen bonds only existed in HSA‒HPyr and HSA‒APyr systems. As the concentration of HPyr/NPyr/APyr/MPyr increased, the proportion of α-helical structures in HSA increased initially and then decreased. The α-helical component of HSA, however, kept rising with the growing concentration of Pyr. Based on the results of synchronous fluorescence spectra, these conformational changes of HSA did not disturb the microenvironment around tryptophan and tyrosine residues. This work is helpful for improving our understanding of the significance of the types of substituents on polycyclic aromatic hydrocarbon‒HSA interactions.