RESUMEN

Photoactive N-hydroxysulfonamides photocaged with the (6-bromo-7-hydroxycoumarin-4-yl)methyl chromophore have been successfully synthesized, and the mechanisms of photodecomposition investigated for two of the compounds. Upon irradiation up to 97% of a diagnostic marker for (H)NO release, sulfinate was observed for the trifluoromethanesulfonamide system. In the absence of a species that reacts rapidly with (H)NO, (H)NO instead reacts with the carbocation intermediate to ultimately generate (E)-BHC-oxime and (Z)-BHC-oxime. Alternatively, the carbocation intermediate reacts with solvent water to give a diol. Deprotonation of the N(H) proton is required for HNO generation via concerted C-O/N-S bond cleavage, whereas the protonation state of the O(H) does not affect the observed photoproducts. If the N(H) is protonated, C-O bond cleavage to generate the parent N-hydroxysulfonamide will occur, and/or O-N bond cleavage to generate a sulfonamide. The undesired competing O-N bond cleavage pathway increases when the volume percentage of water in acetonitrile/water solvent mixtures is increased.

RESUMEN

The emergence of nitroxyl (HNO) as a biological signaling molecule is attracting increasing attention. HNO-based prodrugs show considerable potential in treating congestive heart failure, with HNO reacting rapidly with metal centers and protein-bound and free thiols. A new class of 2-(2-nitrophenyl)ethyl (2-NPE)-photocaged N-hydroxysulfonamides has been developed, and the mechanisms of photodecomposition have been investigated. Three photodecomposition pathways are observed: the desired concomitant C-O/N-S bond cleavage to generate HNO, sulfinate, and 2-nitrostyrene, C-O bond cleavage to give the parent sulfohydroxamic acid and 2-nitrostyrene, and O-N bond cleavage to release a sulfonamide and 2-nitrophenylacetaldehyde. Laser flash photolysis experiments provide support for a Norrish type II mechanism involving 1,5-hydrogen atom abstraction to generate an aci-nitro species. A mechanism is proposed in which the (Z)-aci-nitro intermediate undergoes either C-O bond cleavage to release RSO2NHO(H), concerted C-O/N-S bond cleavage to generate sulfinate and HNO, or isomerization to the (E)-isomer prior to O-N bond cleavage. The pKa of the N(H) of the N-hydroxysulfonamide plays a key role in determining whether C-O or concerted C-O/N-S bond cleavage occurs. Deprotonating this site favors the desired C-O/N-S bond cleavage at the expense of an increased level of undesired O-N bond cleavage. Triplet state quenchers have no effect on the observed photoproducts.

Asunto(s)

RESUMEN

Trifluoromethanesulphonylhydroxamic acid, CF3 SO2 NHOH, is shown to release HNO under physiological pH conditions. A two-step synthesis is presented with the first complete characterization of CF3 SO2 NHOH. This molecule rapidly decomposes in neutral aqueous solution to cleanly release HNO and CF3 SO2- , which was demonstrated using the HNO traps TXPTS and HOCbl, and by 19 F NMR spectroscopy.