Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity

Abstract

A series of diiron/tetrairon compounds containing a S- or a Se-function (2a-d, 4a-d, 5a-b, 6), and the monoiron [FeCp(CO){SeC¹(NMe₂)C²HC³(Me)}] (3) were prepared from the diiron μ-vinyliminium precursors [Fe₂Cp₂(CO)( μ-CO){ μ-η¹: η³-C³(R')C²HC¹N(Me)(R)}]CF₃SO₃ (R = R' = Me, 1a; R = 2,6-C₆H₃Me₂ = Xyl, R' = Ph, 1b; R = Xyl, R' = CH₂OH, 1c), via treatment with S₈ or gray selenium. The new compounds were characterized by elemental analysis, IR and multinuclear NMR spectroscopy, and structural aspects were further elucidated by DFT calculations. The unprecedented metallacyclic structure of 3 was ascertained by single crystal X-ray diffraction. The air-stable compounds (3, 4a-d, 5a-b, 6) display fair to good stability in aqueous media, and thus were assessed for their cytotoxic activity towards A2780, A2780cisR, and HEK-293 cell lines. Cyclic voltammetry, ROS production and NADH oxidation studies were carried out on selected compounds to give insights into their mode of action.

Keywords: bioorganometallic chemistry; diiron complexes; metal-based drugs; selenium; sulphur; vinyliminium ligand.