Development and cellular application of visible-light-controllable HNO releasers based on caged Piloty's acid

Abstract

Nitroxyl (HNO) is a gaseous molecule with unique pharmacological functions distinct from those of nitric oxide. Because HNO is highly reactive with biological molecules, spatiotemporally controllable HNO releasers are required. Herein, we report the first visible-light-controllable HNO releasers, based on caged Piloty's acid, and we demonstrate their applicability in living cells.

Mechanistic Insights into Rapid Generation of Nitroxyl from a Photocaged N-Hydroxysulfonamide Incorporating the (6-Hydroxynaphthalen-2-yl)methyl Chromophore

“…Photoactivatable HNO donors also pave the way for photoactivated delivery of HNO to specific physiological targets . Several classes of photoactive HNO donors have been developed. − The ideal photoactive HNO donor for biological studies would have excellent thermal stability and water solubility, incorporate photocages with a high molar extinction coefficient and photoproduct quantum yields, release HNO and unreactive byproducts cleanly upon visible light excitation, and ideally proceed via a singlet excited state to avoid potential quenching by oxygen.…”

Stoichiometric Nitroxyl Photorelease Using the (6-Hydroxy-2-naphthalenyl)methyl Phototrigger

“…Since HNO rapidly dimerizes in aqueous solution, HNO studies require compounds that release HNO upon demand. The release of HNO from an HNO donor molecule upon photoactivation is very attractive, given that rapid in situ generation of HNO is desirable for kinetic studies on fast reactions of HNO with biomolecules , and that rapid in situ generation of HNO would be useful for biological studies . Several classes of photoactive HNO donors have been developed. − , To the best of our knowledge, 3-phenyl-5-(2-pyrroyl)-1,2,4-oxadiazole-4-oxide has the highest selectivity (99%) for the release of HNO upon light activation .…”

Azanone (HNO): generation, stabilization and detection

“…44 In this case, HNO was released due to an uncaging mechanism and not because of a pH shift. Other examples for photochemical HNO release have also been reported based on the same family of donors 45,46 , caged Piloty's Acid, 47 and even {FeNO} 6 complexes with a pendant thiol moiety. 48 We would like to remind the reader that {MNO} n is the Enemark-Feltham notation, used to avoid assigning oxidation states in transitionmetal nitric oxide (NO) complexes.…”