From Spontaneous to Photo‐Triggered and Photo‐Calibrated Nitric Oxide Donors

Abstract

NO donors have found wide medical use long before the biorelevance of nitric oxide (NO) was unveiled. From glyceryl trinitrate, amyl nitrite and nitroprusside, to nitrosothiols, NONOates and more, a wide variety of chemicals have been employed as nitric oxide donors for treating pathological conditions and investigating the NO biology. Yet, the release kinetics of these classic NO donors are hard‐to‐define and hard‐to‐monitor in biological milieu. Novel NO donors with robustly defined NO release profiles are sought after. These endeavours have introduced a plethora of novel NO donors, including stimulus‐triggered NO donors, fluorophore‐labeled NO donors. The field also sees a recent addition, i. e. photo‐triggered and photo‐calibrated NO donors, whose NO release is photo‐controlled and further accompanied by a fluorescence turn‐on as a built‐in calibration mechanism of NO release. This review provides an overview of the NO biochemistry, as a roadmap for the chemistry of NO donors. The design rationale and the release mechanism of different classes of NO donors were discussed. Some interesting and notable applications were briefly discussed, e. g. super‐resolution localization microscopic imaging of cell structures, and photo‐acoustic probes for disease diagnosis. With joint‐force, these NO donors constitutes a group of indispensable molecular tools of chemical biology and medicine in real applications.

Synthetic, Natural, and Semisynthetic Polymer Carriers for Controlled Nitric Oxide Release in Dermal Applications: A Review

“…Sepsis patients present decreased NO• production, linked to a decreased and inadequate production of arginine. Undernourished infants also present arginine deficiency, which is similarly manifested by lowered nitric oxide production [ 8 , 10 , 15 , 26 , 30 , 31 , 32 , 33 ].…”

“…These pharmacologically active substances that carry nitric oxide are called NO-donors. Ideally, the donors stabilize the radical until the release is required [ 33 , 34 ].…”

“…There are eight molecules that can be metabolized into nitric oxide and that can be used as donors in biological systems (see Figure 1 ). These consist of arginine, metal nitrosyl complexes (M (n−1) -NO + ), N-diazeniumdiolates (NONOates), nitrate ion (NO 3 − ), nitrogen dioxide (NO 2 ), nitrite ion (dioxidonitrate(1-), NO 2 − ), nitrosothiols (RSNO), organic nitrite (RNO 2 ) and organic nitrate (RNO 3 ) [ 33 ]. They can be classified as natural or chemical-occurring, according to their physiological presence.…”

“…Their spontaneous breakdown can be prevented, for instance, by an alkylation that can later be selectively removed by a particular molecule or enzyme. This technology is inspired by fluorescence biosensing chemistry [ 33 ].…”

“…Usually, the alternative is to deactivate NONOates with a photo-labile group. To monitor the localization of the donors microscopically and to control the release of NO•, fluorescence emission has been used [ 33 ].…”