A Photo-triggered and photo-calibrated nitric oxide donor: Rational design, spectral characterizations, and biological applications

Abstract

Nitric oxide (NO) donors are valuable tools to probe the profound implications of NO in health and disease. The elusive nature of NO bio-relevance has largely limited the use of spontaneous NO donors and promoted the development of next generation NO donors, whose NO release is not only stimulated by a trigger, but also readily monitored via a judiciously built-in self-calibration mechanism. Light is without a doubt the most sensitive, versatile and biocompatible method of choice for both triggering and monitoring, for applications in complex biological matrices. Herein, we designed and synthesized an N-nitroso rhodamine derivative (NOD560) as a photo-triggered and photo-calibrated NO donor to address this need. NOD560 is essentially non-fluorescent. Upon irradiation by green light (532 nm), it efficiently release NO and a rhodamine dye, the dramatic fluorescence turn-on from which could be harnessed to conveniently monitor the localization, flux, and dose of NO release. The potentials of NOD560 for in vitro biological applications were also exemplified in in vitro biological models, i.e. mesenchymal stem cell (MSC) migration suppression. NOD560 is expected to complement the existing NO donors and find widespread applications in chemical biological studies.

Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review

“…However, there are no reports on 4-nitro-3-(trifluoromethyl)aniline-based NO photoreleaser for antibiofilm application. N -nitrosoamine-based NO donors are also photo-triggered NO donors and several small molecular N -nitrosoamine-based NO donors have been explored [141,142,143,144,145]. More recently, Hu et al reported a NO releasing micelle bearing visible light responsive NO donors [146].…”

Nitric Oxide Photoreleasers with Fluorescent Reporting

“…[44] With the goal to shift the one-photon absorption towards more biocompatible wavelength, the same group designed compounds 17 and 18 bearing a rhodamine chromogenic core. [45,46] Both non-fluorescent compounds worked very well upon SPE with the biocompatible green light and the NO release can be followed in HeLa cancer cells exploiting the intense red fluorescence of the non-nitrosated by-products. Ultrafast absorption spectroscopy studies carried out on compound 17 confirmed the fast rate of the NO photorelease process, with the homolysis of the NÀ NO bond occurring in less than 7 ps.…”

“…Ultrafast absorption spectroscopy studies carried out on compound 17 confirmed the fast rate of the NO photorelease process, with the homolysis of the NÀ NO bond occurring in less than 7 ps. [45] The feasibility of compound 17 was also studied in mouse mesenchymal stem cells (MSCs), which have attracted great interest due to their therapeutic potential in tissue engineering. [47] Confocal fluorescence imaging of MSCs incubated with 17 and irradiated at two different times, confirming the NO release occurring in the cytosol, with the fluorescence intensity correlated to the dose of NO released (Figure 9B).…”

“…Interestingly this NO photodonor was also proven to modulate the MSCs migration in a wound model (Figure 9C). [45] Biological activity of compound 18 was highlighted through its photodynamic action in inhibiting platelet aggregation and in inducing antibacterial activity against Asperigillus nidulans, one of the fungi model exhibiting NO sensitivity. [46] Introducing specific targeting moieties into the molecular scaffold of these NO photodonors might encourage their localization in selected cellular compartments permit insights to be gained into the effects of NO in such confined bioenvironment.…”

Modulation of the lifespan of C. elegans by the controlled release of nitric oxide

“…Small-molecule N-nitrosated pushpull dyes exhibit sharp onset/offset of NO release, precise dose controllable NO release, and favorable stability against biomacromolecules. [36][37][38][39][40][41][42][43][44] Yet, they still lack a high loading of NO to allow the NO release be adjusted in a large dynamic range for biomanipulation.…”