Potential Disrupting Effects of Wastewater-Derived Disinfection Byproducts on Chinese Rare Minnow (Gobiocypris rarus) Transthyretin: An In Vitro and In Silico Study.

The available information about whether wastewater-derived disinfection byproducts (DBPs) could elicit potential endocrine-related detrimental effects on aquatic organisms was scarce. Herein, the potential disrupting effects and underlying binding mechanism of 14 wastewater-derived aliphatic and aromatic DBPs and 12 other substances on Chinese rare minnow (Gobiocypris rarus) transthyretin (CrmTTR) were tested and revealed by in vitro and in silico methods. The amino acid sequences of CrmTTR were determined, and the recombinant CrmTTR with a molecular mass of 66.3 kDa was expressed and purified. In vitro assay results indicated that eight selected aromatic DBPs exhibited detectable CrmTTR disrupting ability. Meanwhile, six aliphatic DBPs were not CrmTTR binders. Molecular modeling results implied that hydrophobic hydrogen bonds and/or ionic pair interactions were non-negligible. Four binary classification models with high classification performance were constructed. A significant positive linear relationship was observed for the binding affinity data from CrmTTR and human TTR (n = 18, r = 0.922, p < 0.0001). However, the binding affinity for 13 out of 18 tested compounds with CrmTTR was higher than that with human TTR. All the results highlighted that some wastewater-derived DBPs may be potential disruptors on the aquatic organism endocrine system, and interspecies variation should not be neglected in future determination of the potential endocrine disrupting effects of wastewater-derived DBPs.

Human transthyretin binding affinity of halogenated thiophenols and halogenated phenols: An in vitro and in silico study.

Serious harmful effects have been reported for thiophenols, which are widely used industrial materials. To date, little information is available on whether such chemicals can elicit endocrine-related detrimental effects. Herein the potential binding affinity and underlying mechanism of action between human transthyretin (hTTR) and seven halogenated-thiophenols were examined experimentally and computationally. Experimental results indicated that the halogenated-thiophenols, except for pentafluorothiophenol, were powerful hTTR binders. The differentiated hTTR binding affinity of halogenated-thiophenols and halogenated-phenols were observed. The hTTR binding affinity of mono- and di-halo-thiophenols was higher than that of corresponding phenols; while the opposite relationship was observed for tri- and penta-halo-thiophenols and phenols. Our results also confirmed that the binding interactions were influenced by the degree of ligand dissociation. Molecular modeling results implied that the dominant noncovalent interactions in the molecular recognition processes between hTTR and halogenated-thiophenols were ionic pair, hydrogen bonds and hydrophobic interactions. Finally, a model with acceptable predictive ability was developed, which can be used to computationally predict the potential hTTR binding affinity of other halogenated-thiophenols and phenols. Taken together, our results highlighted that more research is needed to determine their potential endocrine-related harmful effects and appropriate management actions should be taken to promote their sustainable use.