Polycystin Channel Complexes.

Polycystin subunits can form hetero- and homotetrameric ion channels in the membranes of various compartments of the cell. Homotetrameric polycystin channels are voltage- and calcium-modulated, whereas heterotetrameric versions are proposed to be ligand- or autoproteolytically regulated. Their importance is underscored by variants associated with autosomal dominant polycystic kidney disease and by vital roles in fertilization and embryonic development. The diversity in polycystin assembly and subcellular distribution allows for a multitude of sensory functions by this class of channels. In this review, we highlight their recent structural and functional characterization, which has provided a molecular blueprint to investigate the conformational changes required for channel opening in response to unique stimuli. We consider each polycystin channel type individually, discussing how they contribute to sensory cell biology, as well as their impact on the physiology of various tissues.

Irritable Bowel Syndrome Therapeutic Has Broad-Spectrum Antimicrobial Activity.

Otilonium bromide is a poorly absorbed oral medication used to control irritable bowel syndrome. It is thought to act as a muscle relaxant in the intestine. Here, we show that otilonium bromide has broad-spectrum antibacterial and antifungal activity, including against multidrug-resistant strains. Our results suggest otilonium bromide acts on enteric pathogens and may offer a new scaffold for poorly absorbed intestinal antimicrobial therapy.

Antibacterial Thiamine inspired silver (I) and gold (I) N-heterocyclic carbene compounds.

Three new coinage metal carbene complexes of silver and gold were synthesized from a thiamine inspired proligand. The compounds were characterized by HRMS, NMR spectroscopy (1H, 19F, 31P and 13C), FT-IR and elemental analysis. The coordination environment around the metal centers was correlated to the diffusion coefficients obtained from DOSY-NMR experiments and was in agreement with the nuclearity observed in the solid-state by single crystal X-ray crystallography. The silver and gold carbene compounds were subjected to MIC studies against a panel of pathogenic bacteria, including multidrug resistant strains, with the gold carbene derivative showing the most potent antimicrobial activity against Gram-positive methicillin resistant Staphylococcus aureus (MRSA).

Ferrocene tethered boramidinate frustrated Lewis pairs: stepwise capture of CO2 and CO.

The synthesis and reactivity of novel ferrocene tethered boramidinate frustrated Lewis pairs (FLPs), capable of the sequential capture of small molecules, is reported. Reactions of 1,1'-dicarbodiimidoferrocenes with different boranes provides access to metallocene tethered FLPs. The reactivity of the boramidinate moieties can be tuned by the nature of the carbodiimido substituents (alkyl vs. aryl) and the borane used in the reduction (9-borabicyclo[3.3.1]nonane [(C8H14)2BH]2vs. bis-pentafluorophenyl borane [(C6F5)2BH]2). The boramidinate FLP arms do not engage in intramolecular reactions, allowing for independent small molecule capture by each FLP. By careful synthetic control, sequential capture of different gaseous small molecules (CO2 and CO or CO2 and CNtBu) by the same bis(boramidinate)ferrocene molecule has been demonstrated.