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.