Controlled Photochemical Release of Nitric Oxide from O²-Naphthylmethyl- and O²-Naphthylallyl-Substituted Diazeniumdiolates

Abstract

The photochemistry of O2-naphthylmethyl- and O2-naphthylallyl-substituted diazeniumdiolates has been investigated. Electron-donating methoxy group substitution is shown to have a significant effect on the observed photochemistry, with the appropriate substitution pattern resulting in efficient diazeniumdiolate photorelease. Observed nitric oxide release rates from these photoprecursors are consistent with those expected for normal thermal dissociation of the diazeniumdiolate in aqueous solutions and show the same pH dependence.

Generation of Oxynitrenes and Confirmation of Their Triplet Ground States

“…[12][13][14][15] We encountered oxynitrene intermediates in our study of the photochemistry of O 2 -substituted diazeniumdiolates 32 during the course of our development of novel photochemical precursors to nitric oxide (NO). [33][34][35] Oxynitrenes have been generated by the oxidation of O-alkylhydroxylamines [3][4][5][6][7][8][9][10][11]36 and by base-catalyzed decomposition of N-sulfonyl-O-alkylhydroxylamines. 4,7 (Analogous oxida- tion reactions of the corresponding amino compounds have been used to generate aminonitrenes 19,37-40 and sulfenylnitrenes.…”

Photosensitive Precursors to Nitric Oxide

“…250 nm that tail out to A = 0 at approximately 320 nm [22]. Thus, to avoid potential complications from secondary photolysis of photoreleased diazeniumdiolates, Bushan et al examined a series of O 2 -naphthylmethyl-and O 2 -naphthylallyl-substituted diazeniumdiolates (10 -18) that can be photolyzed with light of wavelengths ≥350 nm [19].…”

“…Electron-withdrawing substituents in the 5 and 8 positions, and in the 3, 5, and 8 positions for 1-and 2-naphthol, respectively, have been shown to enhance the excited state acidity, indicating that these positions transmit electronic effects most effectively in the excited states of naphthalene derivatives. Thus, electron-donating substituents in these positions were proposed to enhance the formation of a naphthylmethyl or naphthylallyl cation resulting in the desired photorelease of diazeniumdiolate anion 1 [19].…”

“…Moreover, since the rate of NO release from diazeniumdiolate 1 can be controlled by factors such as the substituents R, pH, and temperature, an additional advantageous feature of 14 (and the other derivatives discussed here) is that the flux of NO can likewise be controlled (and varied). This was demonstrated by simply changing the nature of the released diazeniumdiolate from a diethylamine derivative (1 (R = Et)) to a piperidine derivative (1 (NR 2 = piperidinyl), which releases NO at a significantly faster rate) for 17 and 18, respectively [19].…”

Photocalibrated NO Release from N-Nitrosated Napthalimides upon One-Photon or Two-Photon Irradiation

“…Nitric oxide (NO) donors have been routinely employed as the exogenous source of NO in numerous biomedical studies. − Notable examples include organic nitrates, organic nitrites, metal-nitrosyl complexes, diazeniumdiolates (NONOates), C-/N-/O-/S-/metal-nitroso compounds, (benzo/)­furoxans, sydnonimines, and hydroxyamines. − The biological outcome of NO is profoundly influenced by its localization, flux, and dose. − Therefore, it has attracted tremendous attention in developing NO donors, which release NO with a high spatiotemporal control, to facilitate interpretation of the NO involvement in physiological and pathological processes. − However, even the topnotch NO donors (NONOates) are not satisfactory from this perspective. − The decomposition half-lives of many NONOates in simple neutral aqueous buffers have been measured to range from 1.3 min of DMA-NONOate to over 300 min of DPTA-NONOate. However, it is not as widely acknowledged as it should be that these values may not necessarily translate to a complex biological milieu, as the pH, polarity, and temperature of the system are presumably different from those parameters of the simple aqueous buffers.…”