The Stacking Faulted Nature of the Narrow Gap Semiconductor Sc2_{2}Si2_{2}Te6_{6}

Crystals of Sc$_{2}$Si$_{2}$Te$_{6}$ have been grown and its crystal, micro- and electronic structures were investigated. The layered character of the title compound exhibits stacking faults that impede a full structural characterization by single crystal X-ray diffraction due to diffuse scattering. Based on high resolution transmission electron micrographs and diffraction patterns, the stacking faulted nature of the real structure of Sc$_{2}$Si$_{2}$Te$_{6}$ has been revealed. Different stacking models were derived from the idealized, faultless structure and the stacking disorder was quantitatively analyzed by Rietveld refinement of powder X-ray diffraction patterns. An energetic comparison of the stacking models by density functional theory is in line with the experimental observations. Further, the bonding situation was investigated by electronic structure calculations. Sc$_{2}$Si$_{2}$Te$_{6}$ is a narrow gap semiconductor with an indirect band gap of 0.65 eV

Development of ADS051, an oral, gut‐restricted, small molecule neutrophil modulator for the treatment of neutrophil‐mediated inflammatory diseases

Neutrophils are an essential component of the innate immune system; however, uncontrolled neutrophil activity can lead to inflammation and tissue damage in acute and chronic diseases. Despite inclusion of neutrophil presence and activity in clinical evaluations of inflammatory diseases, the neutrophil has been an overlooked therapeutic target. The goal of this program was to design a small molecule regulator of neutrophil trafficking and activity that fulfilled the following criteria: (a) modulates neutrophil epithelial transmigration and activation, (b) lacks systemic exposure, (c) preserves protective host immunity, and (d) is administered orally. The result of this discovery program was ADS051 (also known as BT051), a low permeability, small molecule modulator of neutrophil trafficking and activity via blockade of multidrug resistance protein 2 (MRP2)‐ and formyl peptide receptor 1 (FPR1)‐mediated mechanisms. ADS051, based on a modified scaffold derived from cyclosporine A (CsA), was designed to have reduced affinity for calcineurin with low cell permeability and, thus, a greatly reduced ability to inhibit T‐cell function. In cell‐based assays, ADS051 did not inhibit cytokine secretion from activated human T cells. Furthermore, in preclinical models, ADS051 showed limited systemic absorption (<1% of total dose) after oral administration, and assessment of ADS051 in human, cell‐based systems demonstrated inhibition of neutrophil epithelial transmigration. In addition, preclinical toxicology studies in rats and monkeys receiving daily oral doses of ADS051 for 28 days did not reveal safety risks or ADS051‐related toxicity. Our results to date support the clinical development of ADS051 in patients with neutrophil‐mediated inflammatory diseases