Raman Metabolomics of Candida auris Clades: Profiling and Barcode Identification.

This study targets on-site/real-time taxonomic identification and metabolic profiling of seven different Candida auris clades/subclades by means of Raman spectroscopy and imaging. Representative Raman spectra from different Candida auris samples were systematically deconvoluted by means of a customized machine-learning algorithm linked to a Raman database in order to decode structural differences at the molecular scale. Raman analyses of metabolites revealed clear differences in cell walls and membrane structure among clades/subclades. Such differences are key in maintaining the integrity and physical strength of the cell walls in the dynamic response to external stress and drugs. It was found that Candida cells use the glucan structure of the extracellular matrix, the degree of α-chitin crystallinity, and the concentration of hydrogen bonds between its antiparallel chains to tailor cell walls' flexibility. Besides being an effective ploy in survivorship by providing stiff shields in the α-1,3-glucan polymorph, the α-1,3-glycosidic linkages are also water-insoluble, thus forming a rigid and hydrophobic scaffold surrounded by a matrix of pliable and hydrated ß-glucans. Raman analysis revealed a variety of strategies by different clades to balance stiffness, hydrophobicity, and impermeability in their cell walls. The selected strategies lead to differences in resistance toward specific environmental stresses of cationic/osmotic, oxidative, and nitrosative origins. A statistical validation based on principal component analysis was found only partially capable of distinguishing among Raman spectra of clades and subclades. Raman barcoding based on an algorithm converting spectrally deconvoluted Raman sub-bands into barcodes allowed for circumventing any speciation deficiency. Empowered by barcoding bioinformatics, Raman analyses, which are fast and require no sample preparation, allow on-site speciation and real-time selection of appropriate treatments.

Gap distribution mapping to visualize regions associated with type 1 endoleak in a fenestrated thoracic stent graft.

OBJECTIVES: Our goal was to analyse the relationships between aortic surface irregularity and a type 1 endoleak (T1EL) after a thoracic endovascular repair using the Najuta fenestrated stent graft. METHODS: The patients who were treated using the Najuta stent graft for an intact aortic arch aneurysm at the Saitama Cardiovascular and Respiratory Center between June 2013 and June 2017 were analysed retrospectively. The primary end point was the occurrence of a T1EL. The gap between a virtual aorta and the patient's aortic wall at the stent graft fixation was calculated over the whole circumference at 1 mm intervals, and gap distribution mapping was performed. The rate of freedom from a T1EL was estimated using the Kaplan-Meier method and compared between the patients with or without a continuously malapposed region of >1 mm from the branches to the aneurysm. RESULTS: Twenty-one patients were analysed. During the mean follow-up period of 21.7 months, 4 patients were confirmed to have T1ELs. Three of the T1Els were detected during the perioperative period and occurred through a fenestration. The remaining patient had a T1EL 2 years postoperatively. The gap distribution mapping confirmed the presence of a continuously malapposed region of >1 mm from the cervical branch to the aneurysm postoperatively in 4 patients with T1ELs. Patients who had a continuously malapposed region of >1 mm showed a statistically lower T1EL rate than those without (p < 0.001). Malapposed regions defined using the gap distribution mapping were consistent with flow channels through T1EL fenestrations detected using the perioperative computed tomography data. CONCLUSIONS: The gap distribution mapping could be useful to predict the occurrence of T1ELs in patients with the Najuta stent graft.

Copper-Catalyzed Regioselective Aminothiolation of Aromatic and Aliphatic Alkenes with N-Fluorobenzenesulfonimide and Thiols through Three-Component Radical Coupling.

Copper-catalyzed regioselective aminothiolation of terminal and internal alkenes with N-fluorobenzenesulfonimide and thiols has been developed. The three-component reaction is promoted by the addition of dimethyl sulfide. In addition to aromatic alkenes, aliphatic alkenes are subjected to the reaction, affording various aminothiolation adducts as single regioisomers. The radical process is proposed by preliminary mechanistic studies, involving radical trap and radical clock experiments.

Iron-induced regio- and stereoselective addition of sulfenyl chlorides to alkynes by a radical pathway.

The radical addition of the Cl-S σ-bond in sulfenyl chlorides to various C-C triple bonds has been achieved with excellent regio- and stereoselectivity in the presence of a catalytic amount of a common iron salt. The reaction is compatible with a variety of functional groups and can be scaled up to the gram-scale with no loss in yield. As well as terminal alkynes, internal alkynes underwent stereodefined chlorothiolation to provide tetrasubstituted alkynes. Preliminary mechanistic investigations revealed a plausible radical process involving a sulfur-centered radical intermediate via iron-mediated homolysis of the Cl-S bond. The resulting chlorothiolation adducts can be readily transformed to the structurally complex alkenyl sulfides by cross-coupling reactions. The present reaction can also be applied to the complementary synthesis of the potentially useful bis-sulfoxide ligands for transition-metal-catalyzed reactions.

Palladium-catalyzed regio- and stereoselective chlorothiolation of terminal alkynes with sulfenyl chlorides.

Chlorothiolation of terminal alkynes with sulfenyl chlorides yields anti-adducts without transition-metal catalysts. In sharp contrast, transition-metal-catalyzed chlorothiolation has not been developed to date, possibly because organosulfur compounds can poison catalyst. Herein, the regio- and stereoselective palladium-catalyzed chlorothiolation of terminal alkynes with sulfenyl chlorides is described. syn-Chlorothiolation offers a complementary synthetic route to chloroalkenyl sulfides. 2-Chloroalkenyl sulfides can easily be transformed into various sulfur-containing products, most of which are often found in natural products and pharmaceuticals.