Elsa Anselmi

Improvements of TArgeted multiplex mass spectrometry IMaging.

MALDI mass spectrometers have become popular tools for imaging histological sections. Currently this technology is primarily used for imaging naturally occurring molecules. Here we report on the improvement of TArgeted multiplex MS IMaging (TAMSIM) technology. For TAMSIM we attach photocleavable mass tags to antibodies. Staining histological sections is done analogously to standard immunohistochemical procedures with chemiluminescent or fluorescent detection with the sole difference that multiple antibodies each with a distinct mass tag are used in a single reaction. Mass tags are released from their respective antibodies by a laser pulse at 355 nm without added matrix. After scanning, MS images are created for each tag mass. The enhancements of TAMSIM presented here relate to four elements, the use of an improved generation of tags, their conjugation directly to primary antibodies, the comparison of fresh frozen sections with paraffin embedded ones for the TAMSIM imaging technology and finally, the increase of multiplex detection. Sections of healthy human pancreatic tissue were imaged to visualize different specific biomarkers (synaptophysin, chromogranin, insulin, calcitonin, somatostatin) in neuroendocrine cells of Langerhans islets. The aim was to localize these biomarkers on the tissue sections simultaneously.

Generation of the SCF3 Radical by Photoredox Catalysis: Intra- and Intermolecular Carbotrifluoromethylthiolation of Alkenes

We report the first use of N-trifluoromethylthiosaccharin as the source of SCF3 radical under photoredox catalysis. This allowed an efficient and general visible-light-mediated carbotrifluoromethylthiolation of alkenes. Under the optimized conditions using fac-[Ir(ppy)3 ] as the photocatalyst, various N-aryl acrylamides as well as a wide range of substituted styrenes can readily be difunctionalized in an intra- or intermolecular fashion, affording the corresponding SCF3 -containing products in good to excellent yield. Importantly, the formation of this SCF3 radical along with other key radical intermediates was unambiguously demonstrated thanks to spin trapping/electron paramagnetic resonance (ST/EPR) experiments, which enabled a clear understanding of the reaction mechanism.

Dichlorotrifluoromethoxyacetic Acid: Preparation and Reactivity

We describe the first gram scale preparation of the reagent dichlorotrifluoromethoxyacetic acid. This stable compound is obtained in five steps starting from the cheap diethylene glycol. The reactivity of the sodium salt of this fluorinated acid was also tested and allowed the preparation of new amides.

One-Pot Synthesis of Aryl- and Alkyl S-Perfluoroalkylated NH-Sulfoximines from Sulfides

A general efficient one-pot synthesis of S-perfluoroalkylated NH-sulfoximines from sulfides has been developed using phenyliodine diacetate (PIDA) and ammonium carbamate. Remarkable rate enhancement with trifluoroethanol was observed, presumably due to H-bonding effects. These mild and metal-free conditions are compatible with -CH2 F, -CFCl2 , -CF2 H, -CF2 Br, -C4 F9 , and -CF3 groups, in both the alkyl- and aryl series. Based on a 19 F NMR analysis, a λ6 -acetoxysulfanenitrile intermediate was proposed.

Complete Assignment of H and C NMR Spectra of 1,2,4-Trisubstituted Pyrroles

1,2,4-Trisubstituted pyrroles were synthesized with an original one-pot domino allylic amination/palladium-catalysed Sonogashira cross-coupling and heterocyclisation process. 1H and 13C NMR spectra were assigned for twelve new compounds containing different substituents in positions 1 and 2, and a carboxylic acid or ester group in position 4. Each assignment was based on the combination of one, and two-dimensional experiments (APT, COSY, HMBC).

Synthesis and Reactivity of β,γ-DihalogenatedUnsaturated Acids: Application to the Synthesis of 4-Substituted5H-Furan-2-ones

β,γ-Dihalogenated unsaturated acids were prepared regio- and stereoselectively from allenic acid, and some aspects of their reactivities were studied.