Nitric Oxide Reacts Very Fast with Hydrogen Sulfide, Alcohols, and Thiols to Produce HNO: Revised Rate Constants

The chemical reactivity of NO and its role in several biological processes seem well established. Despite this, the chemical reduction of ^•NO toward HNO has been historically discarded, mainly because of the negative reduction potential of NO. However, this value and its implications are nowadays under revision. The last reported redox potential, E'(NO,H⁺/HNO), at micromolar and picomolar concentrations of ^•NO and HNO, respectively, is between -0.3 and 0 V at pH 7.4. This potential implies that the one-electron-reduction process for NO is feasible under biological conditions and could be promoted by well-known biological reductants with reduction potentials of around -0.3 to -0.5 V. Moreover, the biologically compatible chemical reduction of ^•NO (nonenzymatic), like direct routes to HNO by alkylamines, aromatic and pseudoaromatic alcohols, thiols, and hydrogen sulfide, has been extensively explored by our group during the past decade. The aim of this work is to use a kinetic modeling approach to analyze electrochemical HNO measurements and to report for the first-time direct reaction rate constants between ^•NO and moderate reducing agents, producing HNO. These values are between 5 and 30 times higher than the previously reported k_eff values. On the other hand, we also showed that reaction through successive attack by two NO molecules to biologically compatible compounds could produce HNO. After over 3 decades of intense research, the ^•NO chemistry is still there, ready to be discovered.