The Interaction of HNO With Transition Metal Centers and Its Biological Significance. Insight Into Electronic Structure From Theoretical Calculations

HNO is a biological effector molecule of growing significance that is proposed to act both as a signaling molecule in mammals, but also as a drug that elevates the detrimental effects of heart attack and stroke by preventing reperfusion injuries. Although the endogenous production of HNO has never been shown rigorously, chemists have discovered a number of pathways that nature could use to produce this molecule from NO, many of them involving transition metal centers. In addition, in its potential role as a signaling molecule, transition metal centers, especially heme and nonheme iron sites, are prime candidates as HNO receptors. In this regard, it is also noteworthy that soluble guanylate cyclase has been proposed to be activated by HNO. In this chapter, we elucidate the electronic structure of heme–HNO complexes with a special focus on their potential role in biology. Other recently discovered HNO complexes based on pentacyanoferrate and [Ru II (Me 3 [9]aneN 3 )(bpy)] 2+ are also included. Insight into the electronic structure of all of these HNO complexes is derived from carefully performed quantum-chemical calculations, usually DFT methods, in close correlation to the available experimental (spectroscopic) data. A critical perspective on the successes and failures of DFT in accomplishing this goal is also provided. For this purpose, the ability of different DFT methods to predict (a) accurate binding constants of biologically relevant molecules to ferrous hemes, and (b) the p K a ’s of HNO complexes is evaluated.