Design, Synthesis and Characterization of Synthetic Ion Receptors as Biologically Functional Ion Carriers and Channels

The study of proteins and natural molecules that transport cations and anions across biological membranes has been a major focus of biochemistry and cellular biology for more than a century. The function of ion transporters is vital for all known forms of life. Natural and synthetic transporters can have applications as antimicrobial agents, in nerve impulse transduction and cell signaling. The current work was performed to further the understanding of a diverse array of novel and previously-studied synthetic molecules as membrane-active ion transporters. In the process, important facets such as ion binding capacity, aggregation behavior, ion transport functionality, and antimicrobial activity are investigated. While these studies yield structural and mechanistic insights into our own research group\u27s synthetic systems, they may also aid in understanding both other synthetic ion transporters as well as natural ion carriers and channels. Among the studies that are performed, is the design, synthesis and characterization of members of the dipicolinic dianilide class of compounds as synthetic chloride channels. In originating this project, an array of both known and novel synthetic chloride receptors were modeled computationally. These compounds were selected for their synthetic accessibility and potential use as a chloride transporter. While some of the dipicolinic dianilides or closely-related isophthalic dianilides have been previously reported, few have been investigated for chloride-binding activity and none for chloride transport activity. Chloride binding and transport activity were correlated to the structural variations within the family, which entailed variation of aromatic substituents. This class of molecules are made in a one step synthesis from commercially-available materials. Some members elicit rapid chloride transport activity: over 80% in 10 minutes or less) at low micromolar concentrations. At least one of these select members displays channel functionality in planar bilayers--one of the smallest family of compounds known to do so. Molecular modeling and monitoring aggregation formation by fluorescence spectroscopy reveals that a stack of transporter monomers presents a geometric arrangement conducive of transmembrane pore formation. This class of compounds, among others, is investigated for antimicrobial activity in Gram negative E. coli. While no activity is present for these chloride transporters, co-application with a known antimicrobial cation transporter diminishes the antimicrobial activity of the latter in Gram positive S. epidermidis

What Predicts Adjustment Among College Students? A Longitudinal Panel Study

Previous studies have reported that law students and medical students experience significant distress during their first year. We suspect that freshmen undergraduates might experience similar distress in their transition to college. This study examines the impact of the undergraduate experience on freshmen. Data replicate the declines reported in law and medical students’ psychological and physical health. Negative coping tactics and perfectionism predicted poorer physical health and alcohol use at the end of the year. However, optimism and self-esteem predicted better physical and psychological outcomes

Structurally simple lipid bilayer transport agents for chloride and bicarbonate

A new series of structurally simple compounds containing thiourea groups have been shown by a combination of ion-selective electrode and 13C NMR techniques to be potent chloride-bicarbonate exchange agents that function at low concentration in POPC and POPC/cholesterol membranes.<br/

Towards predictable transmembrane transport: QSAR analysis of anion binding and transport

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