Catalytic Olefin Transpositions Facilitated by Ruthenium N,N,N-Pincer Complexes.

In this report, we demonstrate olefin transposition/isomerization reactions catalyzed by a series of N,N,N-pincer (1,3-bis(2-pyridylimino)isoindoline) Ru-hydride complexes. The protocol proceeds at room temperature for most substrates, achieving excellent yields, regioselectivity, and diastereoselectivity in short reaction times. The air-stable Ru-chloride derivatives of these complexes exhibit comparable reactivity enabling benchtop setup and synthetic versatility. Furthermore, we demonstrate the potential for one-pot cascade sequences of the products derived from the transposition reactions.

Mechanism of Visible Light-Mediated Alkene Aminoarylation with Arylsulfonylacetamides.

Alkene aminoarylation with arylsulfonylacetamides via a visible-light mediated radical Smiles-Truce rearrangement represents a convenient approach to the privileged arylethylamine pharmacaphore traditionally generated by circuitous, multi-step sequences. Herein, we report detailed synthetic, spectroscopic, kinetic, and computational studies designed to interrogate the proposed mechanism, including the key aryl transfer event. The data are consistent with a rate-limiting 1,4-aryl migration occurring either via a stepwise process involving a radical Meisenheimer-like intermediate or in a concerted fashion dependent on both arene electronics and alkene sterics. Our efforts to probe the mechanism have significantly expanded the substrate scope of the transformation with respect to the migrating aryl group and provide further credence to the synthetic potential of radical aryl migrations.

Aryl Transfer Strategies Mediated by Photoinduced Electron Transfer.

Radical aryl migrations are powerful techniques to forge new bonds in aromatic compounds. The growing popularity of photoredox catalysis has led to an influx of novel strategies to initiate and control aryl migration starting from widely available radical precursors. This review encapsulates progress in radical aryl migration enabled by photochemical methods─particularly photoredox catalysis─since 2015. Special attention is paid to descriptions of scope, mechanism, and synthetic applications of each method.

A droplet microfluidic platform for high-throughput photochemical reaction discovery.

The implementation of continuous flow technology is critical towards enhancing the application of photochemical reactions for industrial process development. However, there are significant time and resource constraints associated with translating discovery scale vial-based batch reactions to continuous flow scale-up conditions. Herein we report the development of a droplet microfluidic platform, which enables high-throughput reaction discovery in flow to generate pharmaceutically relevant compound libraries. This platform allows for enhanced material efficiency, as reactions can be performed on picomole scale. Furthermore, high-throughput data collection via on-line ESI mass spectrometry facilitates the rapid analysis of individual, nanoliter-sized reaction droplets at acquisition rates of 0.3 samples/s. We envision this high-throughput screening platform to expand upon the robust capabilities and impact of photochemical reactions in drug discovery and development.

Dyspnea in Patients with Stiff-Person Syndrome.

BACKGROUND: Stiff-person syndrome (SPS) is a rare autoimmune disorder that leads to progressively worsening stiffness and spasm of thoracic and proximal-limb musculature. Dyspnea has been reported but not analyzed in patients with SPS. MATERIALS AND METHODS: For this prospective study, 17 patients were recruited from a university-based neurology clinic. History and exam were performed, demographic information collected and available imaging reviewed. Dyspnea was assessed using vertical visual analog scales (VAS), the University of California San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) and dyspnea "descriptors". Standardized assessments of SPS severity were performed by an experienced neurologist. Forced vital capacity (FVC) spirometric analysis was performed on all patients. RESULTS: Fifteen of 17 patients complained of dyspnea, including dyspnea at rest, with exertion, and disturbing sleep. A restrictive pattern was the most common abnormality noted on spirometry. FVC (r = -0.67; P < 0.01) and forced expiratory volume in 1-second (FEV1) (r = -0.76; P < 0.01) percent predicted correlated with dyspnea measured by VAS over the preceding 2 weeks. Pulmonary function did not correlate with UCSB-SOBQ or standardized measures of SPS severity. CONCLUSIONS: Dyspnea in SPS is common and occurs at rest with exertion and disturbs sleep. The finding of restrictive physiology and correlation between pulmonary function variables and dyspnea support the hypothesis that thoracic cage constriction by rigidity and/or spasm of the muscles of the trunk causes or contributes to the sensation of dyspnea. The possibility of diaphragmatic involvement requires further study.

Mn-Catalyzed Electrochemical Chloroalkylation of Alkenes.

The heterodifunctionalization of alkenes is an efficient method for synthesizing highly functionalized organic molecules. In this report, we describe the use of anodically coupled electrolysis for the catalytic chloroalkylation of alkenes-a reaction that constructs vicinal C-C and C-Cl bonds in a single synthetic operation-from malononitriles or cyanoacetates and NaCl. Knowledge of the persistent radical effect guided the reaction design and development. A series of controlled experiments, including divided-cell electrolysis that compartmentalized the anodic and cathodic events, allowed us to identify the key radical intermediates and the pathway to their electrocatalytic formation. Cyclic voltammetry data further support the proposed mechanism entailing the parallel, Mn-mediated generation of two radical intermediates in an anodically coupled electrolysis followed by their selective addition to the alkene.

Admission chest CT complements fiberoptic bronchoscopy in prediction of adverse outcomes in thermally injured patients.

In burned patients, inhalation injury can result in progressive pulmonary dysfunction, infection, and death. Although bronchoscopy is the standard for diagnosis, it only assesses the proximal airway and does not provide a comprehensive analysis of pulmonary insult. Chest radiographs have not been proven helpful in diagnosis of inhalation injury. Our hypothesis is that a CT scan alone or in conjunction with bronchoscopy can be used as a prognostic tool for critically ill burn patients, especially those with inhalation injury. The authors performed a retrospective study of all patients admitted to the U.S. Army Institute of Surgical Research Burn Center between 2002 and 2008 with chest CT within 24 hours of admission. They divided subjects into two groups, those with evidence of inhalation injury on bronchoscopy and those without. They used a radiologist's score to assess the degree of damage to the pulmonary parenchyma. The primary endpoint was a composite of pneumonia, acute lung injury/acute respiratory distress syndrome, and death. The inhalation injury group consisted of 25 patients and the noninhalation injury group of 19 patients. Groups were not different in age, TBSA burned, and percentage full-thickness burn. By multiple logistic regression, detection of inhalation injury on bronchoscopy was associated with an 8.3-fold increase in the composite endpoint. The combination of inhalation injury on bronchoscopy and a high radiologist's score was associated with a 12.7-fold increase in the incidence of the composite endpoint. Admission CT assists in predicting future lung dysfunction in burn patients.

Bacterial endocarditis presenting with unilateral renal artery occlusion treated with the Rinspirator Thrombus Removal System rinsing and thrombectomy device and suction thrombectomy.

We report a 36-year-old man who presented with unilateral flank pain caused by renal artery occlusion with ischemia and infarction from septic emboli secondary to bacterial endocarditis. We treated the occlusion with a novel rinsing and aspiration device, the Rinspirator Thrombus Removal System (ev3, Plymouth, Minn) and suction thrombectomy, which resulted in significant revascularization of the kidney and relief of symptoms. Postprocedural imaging demonstrated marked improvement in renal vascularization, with only small areas of infarction. This technique may be useful in patients where the embolic material is chronic or thrombolytic agents are contraindicated.

The Chait Trapdoor cecostomy catheter: an alternative access device to pigtail catheters for chronic cholecystostomy drains.

Acute cholecystitis is a well known complication in the critically ill patient population. These patients are often at high risk for morbidity and mortality associated with cholecystectomy. Percutaneous cholecystostomy has been shown to be an effective procedure in the treatment of acute cholecystitis in this patient population. Some patients require prolonged catheter drainage before definitive therapy. In four patients with patent cystic ducts, standard drainage catheters were exchanged for 10.2-F Chait pediatric cecostomy catheters. The low profile of the catheter and the "Trapdoor" feature allow maintenance and increased patient satisfaction while maintaining drainage and access.

Long-term serial analysis of X-chromosome inactivation patterns and JAK2 V617F mutant levels in patients with essential thrombocythemia show that minor mutant-positive clones can remain stable for many years.

Essential thrombocythemia (ET) is heterogeneous with respect to natural history, X-chromosome inactivation patterns (XCIPs), and presence of the V617F mutation in Janus kinase 2 (JAK2). We studied 111 patients with ET; 39% were JAK2 mutant positive, and clone size (percentage mutant JAK2) was concordant with XCIP when constitutive T-cell patterns were taken into account. JAK2 mutant clones were present in both clonal and polyclonal cases as determined by XCIP, and the former had higher mutant JAK2 levels (median 26% versus 16%; P=.001). No change was observed in serial XCIP analysis of 14 polyclonal patients over a median follow-up of 61 months. Furthermore, 18 of 19 mutant-positive patients showed no significant change in mutant JAK2 level over a median follow-up of 47 months. These results suggest that, in many cases of ET, a small stable clone containing a JAK2 mutation can be maintained as a subpopulation for many years.