The effect of ancillary ligands on vasodilatory activity of nitrosyl ruthenium complexes

J Inorg Biochem. 2026 Feb:275:113144. doi: 10.1016/j.jinorgbio.2025.113144. Epub 2025 Nov 6.

Abstract

Sodium nitroprusside (Na2[Fe(CN)5NO], SNP) has long been administered in emergencies to reduce the blood pressure of cardiovascular patients. Despite resolution, NO rapid release and the toxicity of cyanide associated with SNP cause substantial harm. This study investigated three nitrosyl ruthenium complexes for vasodilatory activity, focusing on controlled NO release from a non-toxic compound. Cis-[Ru(bpy)2(5-ain)NO](PF6)3 (5-ainBpy), cis-[Ru(phen)2(5-ain)NO](PF6)3 (5-ainPhen), and cis-[Ru(phen)2(SO3)NO]PF6 (SO3Phen), where bpy = 2,2'-bipyridine, phen = 1,10-phenantroline, and 5-ain = 5-azaindole, were fully characterized by electrochemical and spectroscopic techniques, and showed no toxicity against rat cardiomyoblast (H9c2) and murine fibroblast cells (L929). Vasodilatory assays were conducted on pre-contracted rat thoracic aortic rings using SNP as reference compound. All complexes exhibited efficacies comparable to SNP (from 134 to 146 %), yet only SO3Phen showed a 160-fold lower potency, suggesting that the ancillary ligand 5-azaindole exerts a stronger influence. Kinetic data showed that the maximum efficacy of the vasodilatory activity is reached by 5-ainBpy and 5-ainPhen after 15 and 23 min, respectively, while just 1 min is needed for SNP. For the sulfite complex, only 65 % of relaxation was achieved after 30 min. The results suggest that the vasodilatory activity of the studied complexes is associated with the easiness and rate of the NO release which, in turn, is strongly dependent on the chemical nature of the ancillary ligands occupying the cis position to NO. Current experiments with complexes containing ligands of varying π Lewis acid strength in the cis position to NO are being conducted to further validate the proposed hypothesis.

Keywords: Azaindole; Nitrosyl; Ruthenium; Sulfite; Vasodilation.

MeSH terms

  • Animals
  • Cell Line
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Ligands
  • Mice
  • Nitric Oxide / metabolism
  • Nitroprusside / chemistry
  • Nitroprusside / pharmacology
  • Rats
  • Ruthenium* / chemistry
  • Ruthenium* / pharmacology
  • Vasodilation* / drug effects
  • Vasodilator Agents* / chemical synthesis
  • Vasodilator Agents* / chemistry
  • Vasodilator Agents* / pharmacology

Substances

  • Ruthenium
  • Vasodilator Agents
  • Coordination Complexes
  • Ligands
  • Nitric Oxide
  • Nitroprusside