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We demonstrate a versatile class of nanoscale chemical sensors based on single-stranded DNA (ssDNA) for chemical recognition and single-walled carbon nanotube field effect transistors (SWNT FETs) for electronic read-out. SWNT FETs with a nanoscale coating of ssDNA respond to vapours that cause no detectable conductivity change in bare devices. The gases tested are methanol, trimethylamine, propionic acid, dimethylmethylphosphonate and dinitrotoluene. Sensor responses differ in sign and magnitude for different gases and can be tuned by choice of the ssDNA base sequence. Sensors respond and recover rapidly (seconds), and the sensor surface is self-regenerating. Preliminary results of all-atom molecular dynamics simulations are consistent with experiment. [ABSTRACT FROM AUTHOR]

Tin-based perovskites have very comparable electronic properties to lead-based perovskites and are regarded as possible lower toxicity alternates for solar cell applications. However, the efficiency of tinbased perovskite solar cells is still low and they exhibit poor air stability. Here, we report lead-free tin-based solar cells with greatly enhanced performance and stability using so-called "hollow" ethylenediammonium and methylammonium tin iodide ({en}MASnI3) perovskite as absorbers. Our results show that en can improve the film morphology and most importantly can serve as a new cation to be incorporated into the 3D MASnI3 lattice. When the cation of en becomes part of the 3D structure, a high density of SnI2 vacancies is created resulting in larger band gap, larger unit cell volume, lower trap-state density, and much longer carrier lifetime compared to classical MASnI3. The best-performing {en}MASnI3 solar cell has achieved a high efficiency of 6.63% with an open circuit voltage of 428.67 mV, a short-circuit current density of 24.28 mA cm-2, and a fill factor of 63.72%. Moreover, the {en}MASnI3 device shows much better air stability than the neat MASnI3 device. Comparable performance is also achieved for cesium tin iodide solar cells with en loading, demonstrating the broad scope of this approach. [ABSTRACT FROM AUTHOR]

A series of compounds containing the 2-amino-1,3-thiazol-4(5H)-one core were found to be potent inhibitors of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). One of our lead compounds from this series activated the human nuclear xenobiotic receptor, pregnane X receptor (PXR). To try and mitigate the PXR activity, we prepared analogues of our lead series that contained polar groups on the right-hand side of the thiazolone. Several analogues containing amides or alcohols appended to the C-5 position of the thiazolone showed a significant reduction in PXR activity. Through these structure−activity efforts, a compound containing a tert-alcohol group off the C-5 position, analogue (S)-33a, was found to have an 11β-HSD1 Ki= 35 nM and negligible PXR activity. Compound (S)-33awas advanced into a pharmacodynamic model in cynomolgus monkeys, where it inhibited adipose 11β-HSD1 activity after being orally administered. [ABSTRACT FROM AUTHOR]

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has attracted considerable attention during the past few years as a potential target for the treatment of diseases associated with metabolic syndrome. In our ongoing work on 11β-HSD1 inhibitors, a series of new 2-amino-1,3-thiazol-4(5 H)-ones were explored. By inserting various cycloalkylamines at the 2-position and alkyl groups or spirocycloalkyl groups at the 5-position of the thiazolone, several potent 11β-HSD1 inhibitors were identified. An X-ray cocrystal structure of human 11β-HSD1 with compound 6d( Ki= 28 nM) revealed a large lipophilic pocket accessible by substitution off the 2-position of the thiazolone. To increase potency, analogues were prepared with larger lipophilic groups at this position. One of these compounds, the 3-noradamantyl analogue 8b, was a potent inhibitor of human 11β-HSD1 ( Ki= 3 nM) and also inhibited 11β-HSD1 activity in lean C57Bl/6 mice when evaluated in an ex vivo adipose and liver cortisone to cortisol conversion assay. [ABSTRACT FROM AUTHOR]

We investigated the biocompatibility, specificity, and activity of a ligand−receptor-protein system covalently bound to oxidized single-walled carbon nanotubes (SWNTs) as a model proof-of-concept for employing such SWNTs as biosensors. SWNTs were functionalized under ambient conditions with either the Knob protein domain from adenovirus serotype 12 (Ad 12 Knob) or its human cellular receptor, the CAR protein, via diimide-activated amidation. We confirmed the biological activity of Knob protein immobilized on the nanotube surfaces by using its labeled conjugate antibody and evaluated the activity and specificity of bound CAR on SWNTs, first, in the presence of fluorescently labeled Knob, which interacts specifically with CAR, and second, with a negative control protein, YieF, which is not recognized by biologically active CAR proteins. In addition, current−gate voltage (I−Vg) measurements on a dozen nanotube devices explored the effect of protein binding on the intrinsic electronic properties of the SWNTs, and also demonstrated the devices' high sensitivity in detecting protein activity. All data showed that both Knob and CAR immobilized on SWNT surfaces fully retained their biological activities, suggesting that SWNT−CAR complexes can serve as biosensors for detecting environmental adenoviruses. [ABSTRACT FROM AUTHOR]

11-hydroxysteroid dehydrogenase type 1 (11-HSD1) is the enzyme that converts cortisone to cortisol. A growing body of evidence suggests that selective inhibition of 11-HSD1 could potentially treat metabolic syndrome as well as type 2 diabetes. Through modification of our initial lead 1, we have discovered trifluoromethyl thiazolone 17. This compound had a Kiof 22 nM, possessed low in vivo clearance, and showed a 91% inhibition of adipose 11-HSD1 enzymatic activity in a mouse ex vivo pharmacodynamic model. [ABSTRACT FROM AUTHOR]