Triclosan (TCS) and triclocarban (TCC) are widely used broad spectrum bactericides that are common pollutants of waterways and soils. Methyl triclosan (mTCS) is the predominant bacterial TCS metabolite. Previous studies have shown that TCS disrupts thyroid hormone (TH) action; however, the effects of mTCS or TCC are not known. The present study uses the cultured frog tadpole tail fin biopsy (C-fin) assay and the TH-responsive rat pituitary GH3 cell line to assess the effects of these three chemicals (1-1000 nM) on TH signaling and cellular stress within 48 h. mRNA abundance of TH receptor β, Rana larval keratin type I (TH-response), heat shock protein 30, and catalase (stress-response) was measured using quantitative real-time polymerase chain reaction in the C-fin assay. The TH-responsive gene transcripts encoding growth hormone, deiodinase I, and prolactin were measured in GH3 cells with the heat shock protein 70 transcript acting as a cellular stress indicator. We found alteration of stress indicators at a wide range of concentrations of TCS, mTCS, and TCC in both test systems. mTCS and TCC affected TH-responsive gene transcripts at the highest concentration in mammalian cells, whereas a modest effect included lower concentrations in the C-fin assay. In contrast, TCS did not affect TH-responsive transcripts. These results identify nontarget biological effects of these bacteriocides on amphibian and mammalian cells and suggest the TH-disrupting effects observed for TCS could be mediated through its metabolite.

Abstract:Cumulative formation constants for the interaction of phenylboronic acids with 1,2-diols and structurally related α-hydroxy carboxylic acids were determined by potentiometric titration in aqueous solution. Although there is a significant electronic effect on the acidity of phenylboronic acid (ρ = 2.1), there is no marked electronic effect on the stability of the complexes. Rather, the complexes are significantly destabilized by adjacent anionic groups, by steric interactions across the face of the cyclic boronate ester, and by angle strain within the boronate ester ring. Binding that is nearly independent of pH is observed for some favorably constituted α-hydroxy acid complexes as a result of the relatively high acidity of the acids, which in turn allows tetrahedral boronate complexes to persist in acidic solution (pH < 3).

Here we present a transition metal-free synthesis of a rigid, orthogonally functionalized bicyclic sulfone, starting from readily available reagents. The transformation proceeds via a tandem vinylogous 1,2-addition/anionic oxy-Cope sequence, followed by a second vinylogous ketone addition. Stereochemical assignments suggest that the anionic oxy-Cope reaction proceeds exclusively through a boat-shaped transition state. The product of the two-step sequence can be further functionalized through subsequent chemo- and diastereoselective transformations, suggesting possible applications in medicinal chemistry or materials chemistry.

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Reply to Comment on "Effects of Triclocarban, Triclosan, And Methyl Triclosan on Thyroid Hormone Action and Stress in Frog and Mammalian Culture Systems" I n the comment by Fort et al regarding our recent publication by Hinther et al., 1 the authors expressed concern that our synopsis of their previous work 2 was misrepresenting the results described therein and that acknowledgment or discussion of the supplemental data provided in their response to our letter to the editor regarding that work was lacking. 3,4 We maintain that our synopsis of their manuscript was accurate. In this manuscript, 2 tadpole developmental stage was reported as not significantly different compared to controls at day 21 of triclosan exposure. However, the data presented in the manuscript, when reanalyzed by us 3 and subsequently again by the authors 4 demonstrate that there indeed was a significant acceleration of Xenopus laevis tadpole development due to triclosan exposure. Our Chi square analysis of the frequency data presented in the Fort et al. paper 2 showed clear significance in the three lower of the four concentrations tested (0.6, 1.5, 7.2, and 32.3 μg/L triclosan) compared to control animals (for a detailed rationale and analysis refer to ref 3). Using MannÀWhitney U tests, 4 Fort et al. showed a significant acceleration in development at 0.6 and 7.2 μg/L triclosan. We therefore agree with Fort et al that a statistical acceleration of Xenopus laevis tadpole development occurred.A significant increase in TRβ mRNA transcript levels were observed at 1.5 and 7.2 μg/L triclosan which were observed in stage-matched metamorphic climax animals. 2 This observation was regarded as not biologically significant by the authors. 2 Dismissing this observation as not biologically relevant due to the absence of a linear concentrationÀresponse relationship disregards well-precedented hormone response phenomena: 3 TRβ mRNA perturbation can be transitory (but biologically important) and present itself as an apparent "inverted U" rather than a linear response at a given time point. 5,6 Therefore, the observation of a perturbation in Fort et al. 2 is consistent with the observed developmental acceleration.The supplemental data 4 referred to in the comment was not peer reviewed and provided insufficient information in order to properly assess the assertions presented therein. However, the work has now been published in Toxicological Sciences 7 allowing for a more thorough assessment of the data. The original publication stated in the abstract that "End points measured to evaluate effects on thyroid-mediated metamorphosis including developmental stage, thyroid histology, TRβ expression, DI-2 and DI-3 expression, and thyroid gland T 4 (thyroxine) and plasma T 4 and T 3 (triiodothyronine) levels were not affected by TCS exposure." However, it is evident in the manuscript that three of these thyroid end points did show evidence of thyroid axis disruption (thyroid gland hypertrophy, follicle cell height changes, and alterations of plasma T 4 levels). A de...

Treatment of the sulfone (I) with the ketones (II) and (VIII) leads to keto sulfones via 1,2‐addition and oxy‐Cope rearrangement.

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