Direct and indirect approaches to red-shift photoactivated nitric oxide release

Nitric oxide (NO) is an important biochemical molecule that is endogenously produced to act for instance as neurotransmitter, effect cell growth, or to regulate the immune response. Therapeutic treatment with exogeneous NO is difficult owing to its gaseous and reactive nature and, not surprising, specific molecules to deliver NO have been developed. Amongst the various triggers to deliberately release NO from these NO-releasing molecules, light is the most elegant and allows a high degree of control over the time and location of NO-release. For therapeutic applications, it is necessary to use long-wavelength light, preferably in the red to near infrared region, which is challenging to achieve. This review gives an overview on the various approaches to red-shift the activation wavelength for light-activated NO-release from nitrosoamines, o-substituted nitroarenes, L-arginine, cupferron, or nitrosyl metal complexes. While focusing on single photon excitation events, direct excitation mechanisms are covered as well as photoelectron transfer, energy transfer, chemiluminescence energy transfer, photothermal activation or light-triggered oxidation pathways. For each NO-releaser class, the photochemical release mechanism is discussed, and the biological applications are mentioned.