Triplex Blue-shifting Hydrogen Bonds of ClO₄^–···H–C in the Nanointerlayer of Montmorillonite Complexed with Cetyltrimethylammonium Cation from Hydrophilic to Hydrophobic Properties

In this study, molecular interactions of perchlorate (ClO₄^–), an emerging pollutant, with cetyltrimethylammonium­(CTMA⁺) complexed in the nanointerlayer of negatively charged montmorillonite were characterized using the zeta potentials, FTIR, Raman, and XRD spectroscopy and quantified using quantum mechanical calculations and sorption experiments. We found that blue-shifting hydrogen bonds assisted in the uptake of ClO₄^– from water into the nanointerlayer spacing of CTMA⁺-montmorillonite and were tunable according to CTMA⁺ loading. FTIR spectra presented an obvious 47 cm^–1 blue shift in the C–H vibration coming from the N-terminal methyl group of CTMA⁺ when ClO₄^– was absorbed. Quantum mechanical calculations based on density functional theory demonstrated that triplex blue-shifting hydrogen bonds of C–H···O were formed between the three terminal methyl groups of CTMA⁺ and three oxygen atoms of ClO₄^–. The contribution of blue-shifting hydrogen bonds to perchlorate uptake switched from a ClO₄^–/CTMA⁺ ratio of 0.0453 at low CTMA⁺ loadings to a ClO₄^–/CTMA⁺ ratio of 0.2563 (5.6-fold) at high CTMA⁺ loadings, which can be ascribed to the evolution of the nanointerlayer microenvironments from hydrophilic properties to hydrophobic properties. The blue-shifting hydrogen bond of C–H···O that is tunable with the hydrophobic nature of the organic phase should be recognized to elucidate the biochemical behavior of perchlorate in organisms

Atomic Insights into Distinct Hormonal Activities of Bisphenol A Analogues toward PPARγ and ERα Receptors

Bisphenol A analogues (BPAs) belong to a wide variety of large volume chemicals with diverse applications yet emerging environmental concerns. Limited experimental data have demonstrated that BPAs with different halogenation patterns distinctly affect the agonistic activities toward proliferator-activated receptor (PPAR)­γ and estrogen receptors (ER)­α. Understanding the modes of action of BPAs toward different receptors is essential, however, the underlying molecular mechanism is still poorly understood. Here we probed the molecular recognition process of halogenated BPAs including TBBPA, TCBPA, BPAF, BPC, triBBPA, diBBPA, and monoBBPA toward PPARγ and ERα by molecular modeling, especially the impact of different halogen patterns. Increasing bromination at phenolic rings of BPAs was found highly correlated with electrostatic interactions (<i>R</i>² = 0.978 and 0.865 toward PPARγ and ERα, respectively) and van der Waals interactions (<i>R</i>² = 0.995 and 0.994 toward PPARγ and ERα, respectively). More halogenated phenolic rings at 3,5-positions of BPAs increase the shielding of the hormonally active phenolic OH and markedly decrease electrostatic interactions favorable for agonistic activities toward PPARγ, but unfavorable for agonistic activities toward ERα. The halogenation at the phenolic rings of BPAs exerts more impact on molecular electrostatic potential distribution than halogenation at the bridging alkyl moiety. Different halogenations further alter hydrogen bond interactions of BPAs and induce conformational changes of PPARγ ligand binding domain (LBD) and ERα LBD, specifically affecting the stabilization of helix H12 attributable to the different agonistic activities. Our results indicate that structural variations in halogenation patterns result in different interactions of BPAs with PPARγ LBD and ERα LBD, potentially causing distinct agonistic/antagonistic toxic effects. The various halogenation patterns should be fully considered for the design of future environmentally benign chemicals with reduced toxicities and desired properties

Probing the Molecular Interaction of Triazole Fungicides with Human Serum Albumin by Multispectroscopic Techniques and Molecular Modeling

Triazole fungicides, one category of broad-spectrum fungicides, are widely applied in agriculture and medicine. The extensive use leads to many residues and casts potential detrimental effects on aquatic ecosystems and human health. After exposure of the human body, triazole fungicides may penetrate into the bloodstream and interact with plasma proteins. Whether they could have an impact on the structure and function of proteins is still poorly understood. By using multispectroscopic techniques and molecular modeling, the interaction of several typical triazole fungicides with human serum albumin (HSA), the major plasma protein, was investigated. The steady-state and time-resolved fluorescence spectra manifested that static type, due to complex formation, was the dominant mechanism for fluorescence quenching. Structurally related binding modes speculated by thermodynamic parameters agreed with the prediction of molecular modeling. For triadimefon, hydrogen bonding with Arg-218 and Arg-222 played an important role, whereas for imazalil, myclobutanil, and penconazole, the binding process was mainly contributed by hydrophobic and electrostatic interactions. Via alterations in three-dimensional fluorescence and circular dichroism spectral properties, it was concluded that triazoles could induce slight conformational and some microenvironmental changes of HSA. It is anticipated that these data can provide some information for possible toxicity risk of triazole fungicides to human health and be helpful in reinforcing the supervision of food safety

Low concentrations of <i>o,p’</i>-DDT inhibit PKA but not PKC activity in primary cultures of rat ovarian granulosa cells.

<p>(<b>A</b>) PKA activity (phosphorylated band) in granulosa cells exposed to <i>o,p’</i>-DDT at concentrations of 10⁻¹²−10⁻⁸ M. (<b>B</b>) PKC activity (phosphorylated band) in granulosa cells exposed to <i>o,p’</i>-DDT at concentrations of 10⁻¹²−10⁻⁸ M. The data represented similar results from three independent experiments.</p

Primer sequences for Real-time PCR.

<p>Primer sequences for Real-time PCR.</p

Low concentrations of <i>o,p’</i>-DDT have no effects on cell viability of rat ovarian granulosa cells.

<p>Granulosa cells were exposed to <i>o,p’</i>-DDT (10⁻¹² to 10⁻⁸ M) for 24 h or 48 h and cell viability was measured using MTS assay.</p

Low doses of <i>o,p’</i>-DDT affect the <i>in vivo</i> expression of genes, PGE2 secretion and PKA activity in rat ovaries.

<p>Female rats were received daily i.p. injections of <i>o,p’</i>-DDT at doses of 0.1, 0.5, 1 mg/kg/day for 6 days. Ovaries were collected to isolate the granulosa cells. (<b>A</b>) <i>In vivo</i> expression levels of mRNA for ovarian genes. (<b>B</b>) Levels of PGE2 in rat ovarian tissues. (<b>C</b>) <i>In vivo</i> PKA activity (phosphorylated band) in rat ovarian tissues. (<b>D</b>) <i>In vivo</i> PKC activity (phosphorylated band) in rat ovarian tissues. The results of (<b>A</b>) and (<b>B</b>) were shown as mean ± SEM for three independent experiments performed in triplicate. The data of (<b>C</b>) and (<b>D</b>) represented similar results from three independent experiments. *, <i>ρ</i> <0.05, compared to control.</p

Low concentrations of <i>o,p’</i>-DDT inhibit <i>in vitro</i> gene expression, PGE2 secretion and transcriptional activity of COX-2 promoter in primary cultures of rat ovarian granulosa cells.

<p>(<b>A</b>) <i>In vitro</i> expression levels of mRNA for ovarian genes in granulsa cells exposed to <i>o,p’</i>-DDT at concentrations of 10⁻¹²−10⁻⁸ M. (<b>B</b>) Levels of PGE2 in cultured media of rat granulosa cells exposed to <i>o,p’</i>-DDT at concentrations of 10⁻¹²−10⁻⁸ M. (<b>C</b>) Luciferase activity of COX-2 promoter in granulsa cells exposed to <i>o,p’</i>-DDT at concentrations of 10⁻¹²−10⁻⁸ M. The results were shown as mean ± SEM for three independent experiments performed in triplicate. *, <i>ρ</i> <0.05, compared to control.</p

Disruption of the Hormonal Network and the Enantioselectivity of Bifenthrin in Trophoblast: Maternal–Fetal Health Risk of Chiral Pesticides

Endocrine-disrupting chemicals (EDCs) can interfere with normal hormone signaling to increase health risks to the maternal–fetal system, yet few studies have been conducted on the currently used chiral EDCs. This work tested the hypothesis that pyrethroids could enantioselectively interfere with trophoblast cells. Cell viability, hormone secretion, and steroidogenesis gene expression of a widely used pyrethroid, bifenthrin (BF), were evaluated <i>in vitro</i>, and the interactions of BF enantiomers with estrogen receptor (ER) were predicted. At low or noncytotoxic concentrations, both progesterone and human chorionic gonadotropin secretion were induced. The expression levels of progesterone receptor and human leukocyte antigen G genes were significantly stimulated. The key regulators of the hormonal cascade, GnRH type-I and its receptor, were both upregulated. The expression levels of selected steroidogenic genes were also significantly altered. Moreover, a consistent enantioselective interference of hormone signaling was observed, and <i>S</i>-BF had greater effects than <i>R</i>-BF. Using molecular docking, the enantioselective endocrine disruption of BF was predicted to be partially due to enantiospecific ER binding affinity. Thus, BF could act through ER to enantioselectively disturb the hormonal network in trophoblast cells. These converging results suggest that the currently used chiral pesticides are of significant concern with respect to maternal–fetal health

Direct inhibition of PKA activity by <i>o,p’</i>-DDT.

<p>(<b>A</b>) <i>o,p’</i>-DDT at concentration of 10⁻¹¹ to 10⁻³ M was incubated with 1.25 U purified active catalytic subunit of PKA (control enzyme provided in the PKA PepTag Assay kit). PKA activity was measured using PepTag Assay. The kinase activity was quantitated, as described in <i>Materials and Methods</i>. The results of three independent experiments performed were shown as mean ± SEM. *, <i>ρ</i> <0.05, compared to control. (<b>B</b>) The interaction of <i>o,p’</i>-DDT with PKA. <i>o,p’</i>-DDT was represented in 3D with ball and stick models and the protein was represented in stick models.</p