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Stereoselective Binding of Flurbiprofen Enantiomers and their Methyl Esters to Human Serum Albumin Studied by Time‐Resolved Phosphorescence
Author(s) -
Lammers Ivonne,
LhiaubetVallet Virginie,
Consuelo Jiménez M.,
Ariese Freek,
Miranda Miguel A.,
Gooijer Cees
Publication year - 2012
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22080
Subject(s) - phosphorescence , chemistry , human serum albumin , enantiomer , quenching (fluorescence) , tryptophan , flurbiprofen , stereoselectivity , chirality (physics) , fluorescence , circular dichroism , methylation , stereochemistry , photochemistry , biochemistry , dna , catalysis , medicine , physics , nambu–jona lasinio model , chiral symmetry breaking , amino acid , quantum mechanics , pharmacology , quark
The interaction of the nonsteroidal anti‐inflammatory drug flurbiprofen (FBP) with human serum albumin (HSA) hardly influences the fluorescence of the protein's single tryptophan (Trp). Therefore, in addition to fluorescence, heavy atom‐induced room‐temperature phosphorescence is used to study the stereoselective binding of FBP enantiomers and their methyl esters to HSA. Maximal HSA phosphorescence intensities were obtained at a KI concentration of 0.2 M. The quenching of the Trp phosphorescence by FBP is mainly dynamic and based on Dexter energy transfer. The Stern–Volmer plots based on the phosphorescence lifetimes indicate that ( R )‐FBP causes a stronger Trp quenching than ( S )‐FBP. For the methyl esters of FBP, the opposite is observed: ( S )‐(FBPMe) quenches more than ( R )‐FBPMe. The Stern–Volmer plots of ( R )‐FBP and ( R )‐FBPMe are similar although their high‐affinity binding sites are different. The methylation of ( S )‐FBP causes a large change in its effect on the HSA phosphorescence lifetime. Furthermore, the quenching constants of 3.0 × 10 7 M −1 s −1 of the R ‐enantiomers and 2.5 × 10 7 M −1 s −1 for the S ‐enantiomers are not influenced by the methylation and indicate a stereoselectivity in the accessibility of the HSA Trp to these drugs. Chirality 24:840–846, 2012. © 2012 Wiley Periodicals, Inc.