Comprehensive Insights into the Interactions of Two Emerging Bromophenolic DBPs with Human Serum Albumin by Multispectroscopy and Molecular Docking

Abstract

Disinfection byproducts (DBPs) are of high concern due to their ubiquitous existence in disinfected drinking water and their potential adverse effects on human health. In this study, two bromophenolic DBPs 4-bromophenol (4-BrPh) and 2,4-dibromophenol (2,4-DiBrPh) were selected to investigate their binding interactions with human serum albumin (HSA) using spectroscopic techniques and a molecular docking method. The experimental results demonstrated that both of the DBPs could bind with HSA to form bromophenol–HSA complexes with the HSA secondary structure being changed, primarily relying on hydrogen bonding and van der Waals forces, but 2,4-DiBrPh showed a higher binding affinity. The binding constants of 4-BrPh–HSA and 2,4-DiBrPh–HSA were 2.66 × 103 and 1.83 × 104 M–1 at 310 K, respectively. Molecular docking results revealed the locations of the binding sites for bromophenols on HSA (locating in subdomain IB). In addition, the comparative toxicity of the two bromophenolic DBPs was evaluated with the mammalian cytotoxicity bioassay and the results showed that the LC50 values of 4-BrPh and 2,4-DiBrPh were 3.08 × 10–5 and 1.09 × 10–5 M, respectively. Notably, 2,4-DiBrPh with a higher binding affinity toward HSA also showed a significantly higher toxic potency than 4-BrPh.

Interactions between Human Serum Albumin and Sulfadimethoxine Determined Using Spectroscopy and Molecular Docking

“…Human serum albumin (HSA), the most abundant protein in plasma, is quite versatile in function, and plays a role in maintaining the acid–base balance, regulating osmotic pressure, and catalyzing metabolic reactions [ 7 , 8 ]. In addition, HSA is the primary depot and is involved in the transport of exogenous small molecules throughout the body [ 9 , 10 ], which is, consequently, accompanied by conformational changes in its secondary and tertiary structures.…”

Research Progress of the Endocrine-Disrupting Effects of Disinfection Byproducts

“…There is evidence in toxicological and epidemiological research in cell cultures that haloacetonitriles (HANs), e.g., dibromoacetonitrile (DBAN) and 2,3-dibromopropionitrile (DBPN), can invoke adverse effects on the endocrine system by binding to the human estrogen receptor and androgen receptor [50,67]. Additionally, Nakamura et al [68] reported that halogenated derivatives of E1, E2, E3, and EE2 showed estrogenic activity, interfering with estrogen receptor α, using yeast two-hybrid assays between human and medaka fish (Oryzias latipes), The androgen hormone regulates the androgen signaling pathway via binding with the androgen receptor (AR), and it plays an essential role in the physiological processes of human development and reproduction [92]. Iodoacetic acid (IAA) was observed to show AR binding in vitro [50].…”

Insight into the Molecular Mechanism for the Discrepant Inhibition of Microcystins (MCLR, LA, LF, LW, LY) on Protein Phosphatase 2A

“…As information about the crystal structures of MCs-PP1/PP2A is limited, it is difficult to elucidate the molecular mechanism for the discrepant inhibition of MCs on PP1/PP2A. Homology modeling could evaluate the interactions between structural analogues and macromolecules, and it has been successively used to evaluate the interactions between drugs/contaminants and proteins [19][20][21].…”