Fluorofuroxans: Synthesis and Application as Photoinduced Nitric Oxide Donors

Abstract

The synthesis of 3-and 4-fluorofuroxansi sr eported for the first time. Underp hotoirradiation and physiological conditions, 4-fluorofuroxans with weaker nitric oxide-releasing ability are converted into 3-fluorofuroxans, which show remarkable thiol-mediated nitric oxide-releasing properties, thereby suggesting that 4-fluorofuroxans are potent photoinduced nitric oxide donors.

Study on the Photoinduced Nitric‐Oxide‐Releasing Ability of 4‐Alkoxy Furoxans

“…In all cases, no significant byproduct formation is observed. In contrast to the photo-isomerization of 4fluorofuroxans, where the proportion of the post-isomerization isomer (3-fluorofuroxan) reached 90% at the PS, [6] the photoisomerization of 4-alkoxy furoxans affords a lower proportion of the post-isomerization isomer, 3-alkoxy furoxans (<1-85%). Generally, as the alkoxy substituent (OR 2 ) becomes more electron-withdrawing and the aryl-substituent (R 1 ) becomes more electron-donating, 3-alkoxy furoxan 4 becomes more favored than 4-alkoxy furoxan 3.…”

“…[4] Some furoxans have shown thiol-mediated NO-releasing abilities under physiological conditions. [5] We recently [6] established a synthetic route for both fluorofuroxan regioisomers and found that 3-fluoro-substituted isomer 2 generates a greater amount of NO in the presence of a thiol mediator than the 4-fluorosubstituted isomer 1 (Scheme 1). Furthermore, 3-fluorofuroxan 2 is generated from 4-fluorofuroxan 1 by photochemical isomerization.…”

A Fluorescent Naphthalenediimide-Alkoxyfuroxan Photoinduced Nitric Oxide Donor

“…Previously we have shown that sensitised NO release of anthraquinone-tethered fluorofuroxans under visible light irradiation generates comparable quantities of NO as the lone fluorofuroxan moiety does under UV irradiation. 21,23 Therefore, we assumed this may be the case for an NDI-furoxan molecule as well. We screened potential furoxans by irradiating them with 300-400 nm light in 50 mM pH 7.4 phosphate buffer and compared the NO release after 2 hours of irradiation (Table 1).…”

“…Recently our research group have made use of the NO donor furoxan and synthesised a series of PINODs. 21,22 4-Fluoroand 4-alkoxy-substituted furoxan derivatives displayed isomerization and photoswitchable release of NO under UV irradiation (Scheme 1a). Constrained with the short UV wavelengths required we consolidated on the furoxan PINOD chemistry by tethering a fluorofuroxan to a visible light absorbing water-soluble anthraquinone molecule 5 (Scheme 1b).…”

Synthesis of alkynyl furoxans. Rare carbon–carbon bond-forming reaction on a furoxan ring

“…2 Thus, furoxan has been applied as a building block in hybrid pharmaceutical candidates 3 and switchable NO donors. 4 Most biologically active furoxans reported to date bear one or two carbon substituents on the furoxan ring ( Figure 1). 5 Conventionally, carbon-substituted furoxans were synthesized via the pre-installation of the required carbon substituent on the precursor (e.g.…”