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Novel Roussin's red salt esters as cardiovascular protectors: "Structure-activity" correlations, properties in solid

Оlesya V Pokidova1, Veronika O Novikova2, Nina S Emel'yanova2

  • 1Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, prosp. Akad. Semenova, 1, 142432 Chernogolovka, Moscow Region, Russia; Faculty of Fundamental Physical and Chemical Engineering, Lomonosov Moscow State University M.V. Lomonosov, Leninskie gory, 1, 119991 Moscow, Russia.

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|March 25, 2026
PubMed
Summary

Novel iron complexes release nitric oxide (NO) for prolonged periods. The phenylethanethiolyl complex shows promise for cardiovascular disease treatment due to its biological activity and unique NO release properties.

Keywords:
Adenylate cyclaseAlbuminGuanylate cyclaseMucinNitric oxide donorsTetranitrosyl iron complexes

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Area of Science:

  • Inorganic Chemistry
  • Medicinal Chemistry
  • Biochemistry

Background:

  • Tetranitrosyl iron complexes (NICs) are studied for their potential therapeutic applications.
  • Roussin's red salt esters typically exhibit rapid nitric oxide (NO) release.
  • Understanding ligand effects on NIC stability and NO release is crucial for drug development.

Purpose of the Study:

  • Synthesize and characterize novel binuclear neutral tetranitrosyl iron complexes (NICs).
  • Compare the properties of NICs with phenylmethanethiolyl and phenylethanethiolyl ligands to a known phenylthiolyl NIC.
  • Investigate the nitric oxide (NO) release profile and biological activity of these novel compounds.

Main Methods:

  • Synthesis of novel binuclear neutral tetranitrosyl iron complexes.
  • Spectroscopic analysis and property comparison.
  • In vitro biological activity assays (cyclic nucleotide levels, cytotoxicity on Vero cells).
  • Decomposition mechanism studies in various model systems (aerobic, oxygen-free, DMSO, Tris-HCl buffer).
  • Binding studies with serum albumin and mucin.

Main Results:

  • The phenylethanethiolyl NIC demonstrated prolonged nitric oxide (NO) release in aqueous solutions, unlike typical Roussin's red salt esters.
  • This complex exhibited significant biological activity, including effects on cyclic nucleotide levels and cytotoxicity.
  • Decomposition in various systems preserved the binuclear diamagnetic structure, contrasting with phenylthiolyl complexes.
  • The complex binds to serum albumin and mucin, with mucin binding leading to increased NO groups and EPR signals.

Conclusions:

  • The phenylethanethiolyl NIC is of significant interest due to its prolonged NO release and promising biological activity.
  • This compound shows potential for further development in treating cardiovascular diseases.
  • The unique decomposition pathway and binding interactions warrant further investigation for therapeutic applications.