Binding of hydroxylated polybrominated diphenyl ethers with human serum albumin: Spectroscopic characterization and molecular modeling

Abstract

Three hydroxylated polybrominated diphenyl ethers (OH-PBDEs), 3-OH-BDE-47, 5-OH-BDE-47, and 6-OH-BDE-47, were selected to investigate the interactions between OH-PBDEs with human serum albumin (HSA) under physiological conditions. The observed fluorescence quenching can be attributed to the formation of complexes between HSA and OH-PBDEs. The thermodynamic parameters at different temperatures indicate that the binding was caused by hydrophobic forces and hydrogen bonds. Molecular modeling and three-dimensional fluorescence spectrum showed conformational and microenvironmental changes in HSA. Circular dichroism analysis showed that the addition of OH-PBDEs changed the conformation of HSA with a minor reduction in α-helix content and increase in β-sheet content. Furthermore, binding distance r between the donor (HSA) and acceptor (three OH-PBDEs) calculated using Förster's nonradiative energy transfer theory was <7 nm; therefore, the quenching mechanisms for the binding between HSA and OH-PBDEs involve static quenching and energy transfer. Combined with molecular dynamics simulations, the binding free energies (ΔG ) were calculated using molecular mechanics/Poisson - Boltzmann surface area method, and the crucial residues in HSA were identified.

Methyl divanillate: redox properties and binding affinity with albumin of an antioxidant and potential NADPH oxidase inhibitor

“…43,44 Other example of strong interaction ($10 6 mol À1 L) was related to brominated diphenyl esters. 45 Probably, the increased hydrophobicity of these compounds compared to their monomers precursors is behind of the augmented binding efficacy. This dependence has also been demonstrated to bile salts derivatives.…”

Screening of halogenated phenolic compounds in plasma and serum from marine wildlife

“…Blood plasma and serum are suitable matrices for determining the exposure to HPCs. Blood can be accessed from many species without having to sacrifice the specimen and HPCs accumulated in blood due to their high affinity for plasma proteins (Louis et al 2015), such as serum albumin (Yang et al 2017). However, plasma and serum analyses of HPCs have been proven to be less than trivial and large discrepancies have been observed related to the quality of (amount of hemolysis in) the samples (Dahlberg et al 2014).…”

Using Human Serum Albumin Binding Affinities as a Proactive Strategy to Affect the Pharmacodynamics and Pharmacokinetics of Preclinical Drug Candidates

“…The scaffold itself is often not responsible for contributing to target binding efficacy. As such, we report on the binding interactions of the HSA of prototypical scaffolds of coumarin, , diphenyl ether, , and flavone , that are substituted with common functional groups . From this, we can establish structure–activity relationship (SAR) trends for use in drug discovery projects where an increase or decrease in binding to HSA is needed.…”