Single-Component Photo-Responsive Template for the Controlled Release of NO and H₂S₂

Abstract

Redox signaling molecules include a number of reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS). These molecules work collectively in the regulation of many physiological processes. Understanding the crosstalk mechanisms in these signaling molecules is important but challenging. The development of donor compounds of ROS/RNS/RSS will aid the advances in this field. While many donors that can release one ROS/RNS/RSS have been developed, dual donors that can release two signaling species and facilitate their crosstalk studies are still very rare. Those limited examples lack the ability to precisely control the timing of two releases. In this work, a 2-methoxy-6-naphthacyl-derived tertiary SNO compound, Naph-SNO, was designed and evaluated as the dual donor for NO and H2S2. The 2-methoxy-6-naphthacyl structure was demonstrated to be a novel photoremovable protecting group that could directly uncage C–S bonds. Under the irradiation of lights with different wavelengths (visible or UV), Naph-SNO could release NO and H2S2 in a stepwise manner, or simultaneously (i.e., likely producing the crosstalk product HSNO/HSSNO). In addition, the release of payloads from the donor also produced an end product with blue fluorescence. Therefore, the release process could be easily monitored in “real time.” This controllable photo-triggered release strategy has the potential to be used in the design of other RNS/RSS dual donors.

A Single‐Component Dual Donor Enables Ultrasound‐Triggered Co‐release of Carbon Monoxide and Hydrogen Sulfide

“…For example, Xian and co-workers developed a photo-responsive dual donor based on a single-component template, enabling the stepwise release of NO and H 2 S 2 under consecutive blue and UV light irradiation. [8] These dual donors provided important chemical tools to elucidate the crosstalk of different gasotransmitters. However, considering the limited tissue penetration of light irradiation, it would be imperative to develop single-component dual donors capable of releasing gasotransmitters in pathological tissues with high tissue penetration, which, however, remains a significant challenge.…”

Acetylacetonate Ruthenium Nitrosyls: A Gateway to Nitric Oxide Release in Water under Near-Infrared Excitation by Two-Photon Absorption

“…Phototriggered therapies continue to attract significant research interest nowadays as they bear the opportunity to access an outstanding spatiotemporal control of drug delivery, thus reducing undesirable side effects, thanks to the local activation of phototoxicity on well-localized targets such as solid tumors or wound infections. − The most recent approaches imply the use of two components that are largely innocuous while separated but become highly toxic together. , The combination is composed of low energy light and a photocleavable molecule that releases a cytotoxic agent. In this context, photoactivatable nitric oxide (NO) releasing molecules (photoNORMs) have attracted significant attention due to the appealing properties of the photoreleased molecule . Indeed, NO is a highly lipophilic radical and also perhaps the smallest drug ever delivered following this principle, two characteristics that result in near to barrierless diffusion through cell membranes, allowing for its rapid distribution into the tissues.…”

“…In this context, photoactivatable nitric oxide (NO) releasing molecules (photoNORMs) have attracted significant attention due to the appealing properties of the photoreleased molecule. 9 Indeed, NO is a highly lipophilic 10 radical and also perhaps the smallest drug ever delivered following this principle, two characteristics that result in near to barrierless diffusion through cell membranes, 11 into the tissues. Moreover, NO photorelease is oxygenindependent and thus viable in hypoxic tissues and is capable of inducing cell death by apoptosis, which as opposed to other cell death mechanisms is less prone to lead to an inflammatory response.…”

A Single‐Component Dual Donor Enables Ultrasound‐Triggered Co‐release of Carbon Monoxide and Hydrogen Sulfide

“…Therefore, the activation of donor molecules can occur at different spatial locations, and the release of gasotransmitters can have distinct kinetics, durations, and doses. These limitations can not only complicate the understanding of the synergy of gasotransmitters but also compromise their therapeutic efficacy [8] . To overcome these problems, single‐component donor molecules capable of releasing different gasotransmitters have been recently proposed.…”

“…To overcome these problems, single‐component donor molecules capable of releasing different gasotransmitters have been recently proposed. For example, Xian and co‐workers developed a photo‐responsive dual donor based on a single‐component template, enabling the stepwise release of NO and H 2 S 2 under consecutive blue and UV light irradiation [8] . These dual donors provided important chemical tools to elucidate the crosstalk of different gasotransmitters.…”