Showing papers by "Jennifer R. Hiscock published in 2013"
TL;DR: Quantitative structure–activity relationship (QSAR) analysis and mathematical models show that the experimental transmembrane anion transport ability is mainly dependent on the lipophilicity of the transporter (partitioning into the membrane), but smaller contributions of molecular size and hydrogen bond acidity (anion binding) were also present.
Abstract: The transport of anions across biological membranes by small molecules is a growing research field due to the potential therapeutic benefits of these compounds. However, little is known about the exact mechanism by which these drug-like molecules work and which molecular features make a good transporter. An extended series of 1-hexyl-3-phenylthioureas were synthesized, fully characterized (NMR, mass spectrometry, IR and single crystal diffraction) and their anion binding and anion transport properties were assessed using 1H NMR titration techniques and a variety of vesicle-based experiments. Quantitative structure–activity relationship (QSAR) analysis revealed that the anion binding abilities of the mono-thioureas are dominated by the (hydrogen bond) acidity of the thiourea NH function. Furthermore, mathematical models show that the experimental transmembrane anion transport ability is mainly dependent on the lipophilicity of the transporter (partitioning into the membrane), but smaller contributions of molecular size (diffusion) and hydrogen bond acidity (anion binding) were also present. Finally, we provide the first step towards predictable anion transport by employing the QSAR equations to estimate the transmembrane transport ability of four new compounds.
95 citations
TL;DR: The formation of tren-based tris-urea supramolecular gels in organic solvents is perturbed by the presence of the nerve agent soman providing a new method of sensing the presenceof organophosphorus warfare agents.
45 citations
TL;DR: Studies of sulfamide, phosphoric triamide and thiophosphor triamide-based organocatalysts show that the phosphorus containing systems are effective new hydrogen bonding motifs for the recognition and transport of anions.
42 citations
TL;DR: Efficient neutralization of nerve?agent simulants by 1,3?diindolylureas in a neutral medium was investigated and a mechanism based on the simulant complexation was established.
Abstract: Efficient neutralization of nerve?agent simulants by 1,3?diindolylureas in a neutral medium was investigated (see scheme; DCP=diethylchlorophosphate, DCNP=diethylcyanophosphonate). The rate of hydrolysis of the simulants was found to increase by as much as 45?% in the presence of these compounds. A mechanism based on the simulant complexation was established.
32 citations
TL;DR: An approach for accurate and comparable measurement of host-guest binding affinities is introduced whereby differences in binding strength are measured between two host molecules toward a particular guest under identical solvent conditions, expected to find use in accurate quantification of a wide range of binding processes relevant to supramolecular chemistry.
Abstract: An approach for accurate and comparable measurement of host–guest binding affinities is introduced whereby differences in binding strength (ΔlogKass values) are measured between two host molecules toward a particular guest under identical solvent conditions. Measuring differences instead of absolute values enables obtaining highly accurate results, because many of the uncertainty sources (the solvation/association state of the guest in solution, deviations in solvent composition, etc.) cancel out. As a proof of concept, this method was applied to the measurement of the binding strength of 28 synthetic anion receptors toward acetate in acetonitrile containing 0.5% water. The receptors included differently substituted indolocarbazoles, ureas, thioureas, and some others. Possible deprotonation of more acidic receptors of each compound class by acetate was checked by measuring their acidities (ΔpKa values) relative to acetic acid in the same solvent. A self-consistent (consistency standard deviation 0.04 log ...
29 citations
TL;DR: A series of neutral thiourea receptors were found to mediate the antiport of chloride with a range of biologically relevant carboxylate anions across phospholipid bilayers.
17 citations
TL;DR: Stability constants using 1H NMR techniques highlight the significance of stereoisomerism on anion binding in solution, as cis-receptors bind anions more strongly than trans-receptorors.
Abstract: Bis(thio)urea receptors (1–4) based on 1,2-bisaminocyclohexane are shown to function as transmembrane anion antiporters. The results show that cis-receptors have a greater propensity for anion transport than analogous trans-receptors. Stability constants using 1H NMR techniques highlight the significance of stereoisomerism on anion binding in solution, as cis-receptors bind anions more strongly than trans-receptors.
11 citations