Synthesis of a tetranitrosyl iron complex with unique structure and properties as an inhibitor of phosphodiesterases

Abstract

A novel neutral tetranitrosyl iron complex {[Fe(H₂O)₄]²⁺[FeR₂(NO)₂]₂²⁻}·4H₂O (1) with R = 5-(3-pyridyl)-4H-1,2,4-triazole-3-thiolyls (C₇H₅N₄S), which is a supramolecular ensemble, has been synthesized and studied. As follows from X-ray diffraction analysis, this is an octahedral Fe²⁺complex (Lewis acid) with two monoanionic dinitrosyl groups [FeR₂(NO)₂]⁻ (Lewis base) and 4 water molecules as the ligands. As follows from Mössbauer spectra, the coordinating Fe²⁺ ion is in a low-spin state S = 0, and the dinitrosyl Fe⁺ ion is in a low-spin state S = 1/2. According to the data of EPR spectroscopy, mass-spectrometry and amperometry, complex 1 in solution forms dinitrosyl particles of [Fe(C₇H₆N₄S-H)₂(NO)₂]⁻ composition, which are responsible for NO generation. In addition, complex 1 was shown to be a 5–6 times more efficient phosphodiesterase (PDE) inhibitor at 5 × 10⁻⁵ M and 10⁻⁴ M concentrations than its thioligand. Probable binding sites of the [FeR₂(NO)₂]⁻ ligand for the bovine PDE1B model have been determined by molecular docking and quantum-chemical calculations.