The flexible, electropositive cavity of linear 1,4-diaryl-1,2,3-triazole oligomers provides a suitable host for complexation of various anions. The binding affinities for various combinations of oligomer and anion were determined by (1)H NMR titrations. Effective ionic radius is found to be a primary determinant of the relative binding interactions of various guests, with small but measurable deviations in the case of nonspherical anions. Solvent effects are significant, and the strength of the binding interaction is found to depend directly on the donor ability of the solvent. A picture emerges in which anion binding can be effectively interpreted in terms of a competition between two solvation spheres: one provided by the solvent and a second dominated by a folded cavity lined with electropositive 1,2,3-triazole CH protons. Implications for rigid macrocycles and other multivalent hosts are discussed.

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Layer‐by‐layer (LbL) self‐assemblies have inherent potential as dynamic coatings because of the sensitivity of their building blocks to external stimuli. Here, humidity serves as a feasible trigger to activate the self‐healing of a microporous polyethylenimine/poly(acrylic acid) multilayer film. Microporous structures within the polyelectrolyte multilayer (PEM) film are created by acid treatment, followed by freeze‐drying to remove water. The self‐healing of these micropores can be triggered at 100% relative humidity, under which condition the mobility of the polyelectrolytes is activated. Based on this, a facile and versatile method is suggested for directly integrating hydrophobic drugs into PEM films for surface‐mediated drug delivery. The high porosity of microporous film enables the highest loading (≈303.5 μg cm−2 for a 15‐bilayered film) of triclosan to be a one‐shot process via wicking action and subsequent solvent removal, thus dramatically streamlining the processes and reducing complexities compared to the existing LbL strategies. The self‐healing of a drug‐loaded microporous PEM film significantly reduces the diffusion coefficient of triclosan, which is favorable for the long‐term sustained release of the drug. The dynamic properties of this polymeric coating provide great potential for its use as a delivery platform for hydrophobic drugs in a wide variety of biomedical applications.

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. Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus). Physiol Genomics 35: 273-282, 2008. First published September 2, 2008; doi:10.1152/physiolgenomics.90263.2008.-We investigated the effects of fluoxetine, a selective serotonin reuptake inhibitor, on neuroendocrine function and the reproductive axis in female goldfish. Fish were given intraperitoneal injections of fluoxetine twice a week for 14 days, resulting in five injections of 5 g fluoxetine/g body wt. We measured the monoamine neurotransmitters serotonin, dopamine, and norepinephrine in addition to their metabolites with HPLC. Homovanillic acid, a metabolite in the dopaminergic pathway, increased significantly in the hypothalamus. Plasma estradiol levels were measured by radioimmunoassay and were significantly reduced approximately threefold after fluoxetine treatment. We found that fluoxetine also significantly reduced the expression of estrogen receptor (ER)␤1 mRNA by 4-fold in both the hypothalamus and the telencephalon and ER␣ mRNA by 1.7-fold in the telencephalon. Fluoxetine had no effect on the expression of ER␤2 mRNA in the hypothalamus or telencephalon. Microarray analysis identified isotocin, a neuropeptide that stimulates reproductive behavior in fish, as a candidate gene affected by fluoxetine treatment. Real-time RT-PCR verified that isotocin mRNA was downregulated approximately sixfold in the hypothalamus and fivefold in the telencephalon. Intraperitoneal injection of isotocin (1 g/g) increased plasma estradiol, providing a potential link between changes in isotocin gene expression and decreased circulating estrogen in fluoxetine-injected fish. Our results reveal targets of serotonergic modulation in the neuroendocrine brain and indicate that fluoxetine has the potential to affect sex hormones and modulate genes involved in reproductive function and behavior in the brain of female goldfish. We discuss these findings in the context of endocrine disruption because fluoxetine has been detected in the environment. brain; estrogen receptors; isotocin; microarray; Prozac FLUOXETINE (PROZAC), a selective serotonin reuptake inhibitor (SSRI) (46), has been used in several studies in fish to investigate the serotonergic modulation of the endocrine system (55). A racemic mixture of two lipophilic enantiomers, fluoxetine is metabolized by cytochrome P-450 isoenzymes to the active metabolite norfluoxetine (46). In humans, fluoxetine is primarily excreted in urine as ϳ20%-30% unchanged parent compound, while metabolites are largely excreted as pharmacologically active norfluoxetine and inactive fluoxetine glucuronide (62).Fluoxetine also has effects on reproduction in several vertebrates. For example, in the goldfish (Carassius auratus), combined intraperitoneal administration of 10 g/g fluoxetine and 10 g/g serotonin (5-HT) elevated luteinizing hormone (LH) levels relative to 5-HT administration alone 2 h after treatment (55). Japanese medaka (Oryzias latipes) exposed to waterborne 0.1 and 0.5 g/l fluoxetine for 4 wk sh...