Strain-promoted click chemistry of nucleosides and nucleotides with an azido group directly attached to the purine and pyrimidine rings with various cyclooctynes in aqueous solution at ambient temperature resulted in efficient formation (3 min - 3 h) of fluorescent, light-up, triazole products. The 2- and 8-azidoadenine nucleosides reacted with fused cyclopropyl cyclooctyne, dibenzylcyclooctyne or monofluorocyclooctyne to produce click products functionalized with hydroxyl, amino, N-hydroxysuccinimide, or biotin moieties. The 5-azidouridine and 5-azido-2′-deoxyuridine were similarly converted to the analogous triazole products in quantitative yields in less than 5 minutes. The 8-azido-ATP quantitatively afforded the triazole product with fused cyclopropyl cyclooctyne in aqueous acetonitrile (3 h). The novel triazole adducts at the 2 or 8 position of adenine or 5-position of uracil rings induce fluorescence properties which were used for direct imaging in MCF-7 cancer cells without the need for traditional fluorogenic reporters. FLIM of the triazole click adducts demonstrated their potential utility for dynamic measuring and tracking of signaling events inside single living cancer cells.

Radical-mediated thiodesulfonylation of the vinyl and (α-fluoro)vinyl sulfones, derived from aldehydes and ketones, with aryl thiols in organic or aqueous medium provided access to vinyl and (α-fluoro)vinyl sulfides. The vinyl sulfides were formed predominantly with E stereochemistry independent of the stereochemistry of the starting vinyl sulfones. KeywordsFluoroalkenes; Radical reactions; Vinyl sulfides; α-Fluoro vinyl sulfides; Vinyl sulfones Vinyl sulfides are valuable tools in organic synthesis and are used as enolate ion equivalents, 1 as components of [2+2] cyclo-additions, 2 and as substrates in transition metal catalyzed carbon-carbon bond forming reactions.3 Methods for the synthesis of 1-alkenyl sulfides include Wittig reaction,4 ionic and radical additions of thiols to alkynes,5 coupling of 1-alkenyl halides with thiols, 6-9 and transition metal catalyzed anti-Markovnikov hydrothiolation 9-12 of alkynes with arenethiols and alkanethiols to produce E isomers, including hydrothiolation in water medium. 13 Vinyl sulfonium ions, generated via the biological methylation of the corresponding vinyl sulfides act as inhibitors of thioether S-methyltransferase 14 and proteolytic enzyme papain. 15 They are highly reactive towards nucleophiles and bind covalently to DNA, RNA and proteins in vivo. 16 Moreover, vinyl sulfonium salts are more electrophilic than the corresponding vinyl sulfones, which are known for their ability to inhibit cysteine proteases. 17,18 The (α-halo)vinyl sulfides can be prepared by Wittig-Horner reactions with diethyl chloro (phenylthio)-methanephosphonate 19 or by addition of the hydrogen halides (HI, HBr and HCl) to acetylenic sulfides (chalcogenides).20 The regioselectivity and stereoselectivity of such additions were improved when equivalent quantities of hydrogen halide, generated in situ from trimethylsilyl halides and anhydrous methanol, were utilized 21 instead of excess aqueous HX or saturated gaseous HX in benzene. The (α-halo)vinyl sulfides have been employed in Stille, 21, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Herein, we report stereoselective radical-mediated thiodesulfonylations of vinyl and (α-fluoro) vinyl sulfones with aryl thiols to provide access to vinyl and (α-fluoro)vinyl sulfides. Such thiodesulfonylation provides a flexible alternative to the hydrothiolation of alkynes with thiols under radical or metal catalysis conditions. It also offers convenient preparations of (α-fluoro) vinyl sulfides -a class of interesting fluoroalkenes which remain unexplored. 34 The thiodesulfonylation can be also viewed as re...

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This dissertation, written by Jessica Zayas, and entitled Strain Promoted Click Chemistry of 8-Azidopurine and 5-Azidopyrimidine Nucleosides and Nucleotides with Cyclooctynes and Applications to Living Cell Imaging, having been approved in respect to style and intellectual content, is referred to you for judgment.We have read this dissertation and recommend that it be approved. The SPAAC methodology developed has also been applied to study the cellular targets in protozoal parasite, Trichomonas vaginalis and bacteria, Pseudomonas aeruginosa. The 9-(2-deoxy-2-fluoro-β,D-arabino-furanosyl)adenine (arabino-F-Ado) was modified with an azido moiety at the C8 position for use in click chemistry. Tagging and subcellular localization studies using azido modified arabino-F-Ado could provide insight into the mechanism of action of arabino-F-Ado. _______________________________________

Thioethers Q 0580 Radical-Mediated Thiodesulfonylation of the Vinyl Sulfones: Access to (α-Fluoro)vinyl Sulfides. -[and vinyl sulfides]. -(SACASA, P. R.; ZAYAS, J.; WNUK*, S. F.; Tetrahedron Lett. 50 (2009) 38, 5424-5427; Dep. Chem. Biochem., Fla. Int. Univ., Miami, FL 33199, USA; Eng.) -Mais 52-096