Application of Chlorosulfonyl Isocyanate (CSI) in the Synthesis of Fused Tetracyclic Ketone Ring Systems.

Chlorosulfonyl isocyanate (CSI) is a complex reagent capable of facilitating numerous synthetic transformations, including lactam/lactone formation, sulfonylation, Friedel-Crafts-type acylations, and cycloadditions. Annulation reactions to form nitrogen-, oxygen-, and sulfur-bearing heterocycles have been observed with CSI; however, the application of CSI toward the generation of fused cyclic ketone ring systems has not been previously reported. A serendipitous discovery of the pertinence of CSI occurred during a structure-activity relationship campaign around our established lead benzosuberene-based molecule that functions as a potent inhibitor of tubulin polymerization.

Identification and characterization of a nonbiological small-molecular mimic of a Zika virus conformational neutralizing epitope.

Antigenic similarities between Zika virus (ZIKV) and other flaviviruses pose challenges to the development of virus-specific diagnostic tools and effective vaccines. Starting with a DNA-encoded one-bead-one-compound combinatorial library of 508,032 synthetic, non-natural oligomers, we selected and characterized small molecules that mimic ZIKV epitopes. High-throughput fluorescence-activated cell sorter-based bead screening was used to select molecules that bound IgG from ZIKV-immune but not from dengue-immune sera.

Oxygen-Sensing Chemiluminescent Iridium(III) 1,2-Dioxetanes: Unusual Coordination and Activity.

Next generation chemiluminescent iridium 1,2-dioxetane complexes have been developed which consist of the Schaap's 1,2-dioxetane scaffold directly attached to the metal center. This was achieved by synthetically modifying the scaffold precursor with a phenylpyridine moiety, which can act as a ligand. Reaction of this scaffold ligand with the iridium dimer [Ir(BTP)(μ-Cl)] (BTP = 2-(benzo[]thiophen-2-yl)pyridine) yielded isomers which depict ligation through either the cyclometalating carbon or, interestingly, the sulfur atom of one BTP ligand.

Non-Invasive Evaluation of Acute Effects of Tubulin Binding Agents: A Review of Imaging Vascular Disruption in Tumors.

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely fragile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis.

Synthesis and biological evaluation of structurally diverse α-conformationally restricted chalcones and related analogues.

Numerous members of the combretastatin and chalcone families of natural products function as inhibitors of tubulin polymerization through a binding interaction at the colchicine site on β-tubulin. These molecular scaffolds inspired the development of many structurally modified derivatives and analogues as promising anticancer agents. A productive design blueprint that involved molecular hybridization of the pharmacophore moieties of combretastatin A-4 () and the chalcones led to the discovery of two promising lead molecules referred to as and .

Behavioral Disturbance Causing Sudden Respiratory Distress in a 3-Year-Old After Tracheocutaneous Fistula Closure: A Case Report.

A 3-year-old boy underwent tracheostomy at age 5 months for respiratory failure. The tracheostomy tube was removed a year later but a tracheocutaneous fistula developed requiring fistulectomy and primary skin closure. After an initial uneventful course in the postanesthesia care unit, the patient became agitated, began to scream, and suddenly developed rapidly progressing subcutaneous emphysema over his chest, face, and abdomen.

Bioreductively activatable prodrug conjugates of phenstatin designed to target tumor hypoxia.

A variety of solid tumor cancers contain significant regions of hypoxia, which provide unique challenges for targeting by potent anticancer agents. Bioreductively activatable prodrug conjugates (BAPCs) represent a promising strategy for therapeutic intervention. BAPCs are designed to be biologically inert until they come into contact with low oxygen tension, at which point reductase enzyme mediated cleavage releases the parent anticancer agent in a tumor-specific manner.

Reliability of a faculty evaluated scoring system for anesthesiology resident applicants (Original Investigation).

Study Objective: To assess reliability and reproducibility of a recently instituted anesthesiology resident applicant interview scoring system at our own institution.

Design: Retrospective evaluation of 2 years of interview data with a newly implemented scoring system using randomly assigned interviewing faculty.

Setting: Interview scoring evaluations were completed as standard practice in a large academic anesthesiology department.