The useful aspects of nitric oxide (NO) are nowadays widely known. Due to the need for this molecule in the maintenance of homeostasis, NO-releasing compounds are tested every year to optimize its levels in a patient suffering from low NO production. This manuscript is an update of some important historical concerns about nitrosyl complexes having the ability to act as NO-releasing compounds under the influence of different chemically modified environments. At present, the search for efficient and less harmful NO-releasing molecules at desirable targets and concentrations has gained considerable momentum in nitrosyl chemistry. Iron, ruthenium, and manganese nitrosyls have been investigated elitely to disentangle their electronic transition (excitation) under visible light to act as NO donors without harming the healthy cells of a target. There is much evidence supporting the increase of NO lability if amino acids are used as complexing ligands, the design of a reduction center close to an NO grouping, and the development of porphyrin system-based nitrosyl complexes. From the overall survey, it may be concluded that the desirable properties of such scaffolds need to be evaluated further to complement the biological milieu.
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