Related Experiment Video
Updated: May 16, 2026

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
The trans effect of nitroxyl (HNO) in ferrous heme systems: implications for soluble guanylate cyclase activation by
Lauren E Goodrich1, Nicolai Lehnert
1Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract:
Soluble guanylate cyclase (sGC) is the primary mammalian nitric oxide (NO) sensor. Through the strong thermodynamic σ-trans effect of NO, binding of NO at the distal side of the ferrous heme induces cleavage of the proximal FeN(His) bond, activating the catalytic domain of the enzyme. It has been proposed that nitroxyl (HNO) is also capable of activating sGC, but the key question remains as to whether HNO can induce cleavage of the FeN(His) bond. Here we report calculated binding constants for 1-methylimidazole (MI) to [Fe(P)(X)] (P=porphine(2-)) where X=NO, HNO, CO, and MI to evaluate the trans interaction of these groups, X, with the proximal imidazole (histidine) in sGC. Systematic assessment of DFT methods suggests that the prediction of accurate MI binding constants is critically dependent on the inclusion of van der Waals interactions (-D functionals). Calculated (B3LYP-D/TZVP) MI binding constants for X=NO and MI are 110 and 5.6 × 10(5)M(-1), respectively, predicted only one order of magnitude higher than the corresponding experimentally determined values. MI binding constants where X=HNO and CO are consistently predicted to be essentially equal and ~six orders of magnitude larger than those of NO, indicating that CO and HNO mediate a weak thermodynamic trans effect in this system. Orbital analysis of the key σ-bonding orbital, π*(h)_d(z2), and comparison of FeN(MI) bond lengths support this prediction. This suggests that HNO does not induce a σ-trans effect strong enough to promote cleavage of the FeN(His) bond-a key step in the activation of sGC.
Related Concept Videos
Nitric Oxide Signaling Pathway
1° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Overview
The nitrous acid is unstable. Hence, it is formed in situ from a solution of sodium nitrite and cold aqueous acids such as hydrochloric or sulfuric acid. In an acidic solution, the –OH group of nitrous acid undergoes protonation to give oxonium ion, followed by water loss...
2° Amines to N-Nitrosamines: Reaction with NaNO2
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H
Nuclear Overhauser Enhancement (NOE)
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3

