Azulene-Derived Fluorescent Probe for Bioimaging: Detection of Reactive Oxygen and Nitrogen Species by Two-Photon Microscopy.

Two-photon fluorescence microscopy has become an indispensable technique for cellular imaging. Whereas most two-photon fluorescent probes rely on well-known fluorophores, here we report a new fluorophore for bioimaging, namely azulene. A chemodosimeter, comprising a boronate ester receptor motif conjugated to an appropriately substituted azulene, is shown to be an effective two-photon fluorescent probe for reactive oxygen species, showing good cell penetration, high selectivity for peroxynitrite, no cytotoxicity, and excellent photostability.

Atomic dispensers for thermoplasmonic control of alkali vapor pressure in quantum optical applications.

Alkali metal vapors enable access to single electron systems, suitable for demonstrating fundamental light-matter interactions and promising for quantum logic operations, storage and sensing. However, progress is hampered by the need for robust and repeatable control over the atomic vapor density and over the associated optical depth. Until now, a moderate improvement of the optical depth was attainable through bulk heating or laser desorption - both time-consuming techniques. Here, we use plasmonic nanoparticles to convert light into localized thermal energy and to achieve optical depths in warm vapors, corresponding to a ~16 times increase in vapor pressure in less than 20 ms, with possible reload times much shorter than an hour. Our results enable robust and compact light-matter devices, such as efficient quantum memories and photon-photon logic gates, in which strong optical nonlinearities are crucial.

Magnetic coupling in a hybrid Mn(ii) acetylene dicarboxylate.

The design of ligands that mediate through-bond long range super-exchange in metal-organic hybrid materials would expand chemical space beyond the commonly observed short range, low temperature magnetic ordering. Here we examine acetylene dicarboxylate as a potential ligand that could install long range magnetic ordering due to its spatially continuous frontier orbitals. Using a known Mn(ii)-containing coordination polymer we compute and measure the electronic structure and magnetic ordering. In this case, the latter is weak owing to the sub-optimal ligand coordination geometry, with a critical temperature of 2.5 K.

Catalytic Amine Oxidation under Ambient Aerobic Conditions: Mimicry of Monoamine Oxidase†B.

The flavoenzyme monoamine oxidase (MAO) regulates mammalian behavioral patterns by modulating neurotransmitters such as adrenaline and serotonin. The mechanistic basis which underpins this enzyme is far from agreed upon. Reported herein is that the combination of a synthetic flavin and alloxan generates a catalyst system which facilitates biomimetic amine oxidation. Mechanistic and electron paramagnetic (EPR) spectroscopic data supports the conclusion that the reaction proceeds through a radical manifold. This data provides the first example of a biorelevant synthetic model for monoamine oxidase B activity.

Adamantyl ethanone pyridyl derivatives: potent and selective inhibitors of human 11ß-hydroxysteroid dehydrogenase type†1.

Elevated levels of active glucocorticoids have been implicated in the development of several phenotypes of metabolic syndrome, such as type 2 diabetes and obesity. 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) catalyses the intracellular conversion of inactive cortisone to cortisol. Selective 11ß-HSD1 inhibitors have shown beneficial effects in various conditions, including diabetes, dyslipidemia and obesity. A series of adamantyl ethanone pyridyl derivatives has been identified, providing potent and selective inhibitors of human 11ß-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11ß-HSD1 and are selective for this isoform, with no activity against 11ß-HSD2 and 17ß-HSD1. Structure-activity relationship studies reveal that an unsubstituted pyridine tethered to an adamantyl ethanone motif through an ether or sulfoxide linker provides a suitable pharmacophore for activity. The most potent inhibitors have IC50 values around 34-48 nM against human 11ß-HSD1, display reasonable metabolic stability in human liver microsomes, and weak inhibition of key human CYP450 enzymes.

Discovery of adamantyl heterocyclic ketones as potent 11ß-hydroxysteroid dehydrogenase type†1 inhibitors.

11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) plays a key role in converting intracellular cortisone to physiologically active cortisol, which is implicated in the development of several phenotypes of metabolic syndrome. Inhibition of 11ß-HSD1 activity with selective inhibitors has beneficial effects on various conditions, including diabetes, dyslipidemia and obesity, and therefore constitutes a promising strategy to discover novel therapies for metabolic and cardiovascular diseases. A series of novel adamantyl heterocyclic ketones provides potent and selective inhibitors of human 11ß-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11ß-HSD1 and are selective with no activity against 11ß-HSD2 and 17ß-HSD1. Selected potent 11ß-HSD1 inhibitors show moderate metabolic stability upon incubation with human liver microsomes and weak inhibition of human CYP450 enzymes.

Discovery of adamantyl ethanone derivatives as potent 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors.

11Beta-hydroxysteroid dehydrogenases (11beta-HSDs) are key enzymes regulating the pre-receptor metabolism of glucocorticoid hormones. The modulation of 11beta-HSD type 1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue-specific glucocorticoid action by regulating 11beta-HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11beta-HSD1. The most active compounds identified (52, 62, 72, 92, 103 and 104) display potent inhibition of 11beta-HSD1 with IC(50) values in the 50-70 nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in vivo studies. Comparison of the publicly available X-ray crystal structures of human 11beta-HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor.