Structure-based design of bacterial transglycosylase inhibitors incorporating biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties.

Transglycosylase (TGase) is essential to biosynthesis of peptidoglycan for formation of bacterial cell wall. Moenomycin is a potent TGase inhibitor, but not used in clinic treatment due to its poor pharmacokinetics. The E-F disaccharide, phosphoglycerate and lipid tail in moenomycin are crucial elements for TGase inhibition and antibacterial activity. Based on this scaffold, a series of truncated mimics comprising biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties were designed to test their TGase inhibitory activity. In this design, the phosphorylpropanoate group is a surrogate of phosphoglycerate with improved stability. A library of lipid tails can be constructed by a straightforward approach using Cu(I)-catalyzed (3 + 2) cycloaddition reactions, and the as-synthesized triazole ring can provide additional hydrogen bonds in the TGase active site. Our molecular docking experiments reveal that the biphenyl group provides π-π and π-cation interactions to act as a simplified alternative of the C-E disaccharide in moenomycin. To play the role of the oxonium transition state in transglycosylation, the amine linker exists as a positively charged species in physiological condition to attain electrostatic interactions with acidic residues. In this study, two biphenyl-linked 2-alkoxy-3-phosphorylpropanoate compounds (8 and 10) are found to exhibit modest inhibitory activity (IC50 ≈ 150 µM) against the TGase of Acinetobacter baumannii and good antibacterial activity against Staphylococcus aureus (MIC = 6.3 µM).

A simple and highly selective receptor for iodide in aqueous solution.

We synthesized a simple fluorescent receptor 3 bearing two boronic acid groups as recognition sites. The recognition behaviour of receptor 3 towards various anions was evaluated in THF/H(2)O (1:1, v/v) solution. Receptor 3 showed high selectivity for iodide among a series of anions. Fluorescence spectroscopy and computational calculations revealed that the electrostatic interaction played a crucial role in its high selectivity for iodide.

Synthesis of highly selective indole-based sensors for mercuric ion.

Two indole-based fluorescent chemosensors 1 and 2 were prepared and investigated characteristic features with transition metal ions. Sensors 1 and 2 were selective for Hg(2+) ion, among a series of metal ions, in aqueous ethanol (H(2)O-EtOH, 1:2, v/v) with association constants of 5.74 × 10(3) and 4.46 × 10(3) M(-1) and detection limits of 7.4 and 6.8 µM, respectively. Computational results revealed that sensor 1 or 2 with Hg(2+) ion formed 1:1 complex with a central, sandwich-coordinated Hg(2+) ion. Computational calculations provided evidence that a sandwich-coordinated Hg(2+) ion center was formed and the polyoxyethylene spacer acted as a scaffold for bringing functional ligands into a suitable geometry.

A pyrenyl-appended triazole-based ribose as a fluorescent sensor for Hg2+ ion.

For the efficient detection of toxic trace metal ions, two pyrenyl-appended triazole-based d-ribose fluorescent chemosensors 6 and 7 were prepared and their fluoroionophoric properties toward transition metal ions were investigated. Chemosensors 6 and 7 exhibit highly selective recognition toward Hg(2+) ion among a series of tested metal ions in CH(2)Cl(2)/MeOH solution. The association constants of 6 and 7 are calculated to be 1.73 × 10(5)M(-1) and 4.44 × 10(5)M(-1), respectively. Both 6 and 7 formed complexes with the Hg(2+) ion at a 1:1 ligand-to-metal ratio with a detection limit of 10-15 µM Hg(2+). Computational analysis demonstrated that the Hg(2+) ion occupied the coordination center of 6 with N(2) and N(3) atoms in two triazole groups, thus separating and distorting the two parallel pyrenes away from each other.