Novel ferrocene imide derivatives: synthesis, conformational analysis and X-ray structure.

The synthesis and structural characterization of the ferrocene imide derivatives Fc-CO-NH-CO-Me (4), Fc-CO-NH-CO-Fc (7) and Fc-CO-NH-CO-Fn-CO-NH-CO-Fc (8) have been reported. The mononuclear, dinuclear and trinuclear ferrocene imides were prepared by the reaction of ferrocenecarboxamide (3), with acetyl chloride, ferrocenecarbonyl chloride (2) and ferrocene-1,1'-(dicarbonyl chloride) (6), respectively. IR spectroscopic analysis revealed the absence of intramolecular hydrogen bonds in solutions of imides 4, 7 and 8. The crystal packing of N-acetylferrocenecarboxamide (4) is characterized by N-H⋯O hydrogen bonds forming centrosymmetric dimers, while the molecules of its homologue N-methylferrocenecarboxamide (5) are self-assembled by intermolecular N-H⋯O bonds into infinite chains. A detailed conformational analysis (DFT study) suggests the cis-trans configuration of ferrocene imide derivative 7 in solution. The effect of different substituents attached to bridged imide nitrogen on conformational properties of bis-ferrocenyl imides was further investigated and results compared to the existing experimental data.

The conjugates of ferrocene-1,1'-diamine and amino acids. A novel synthetic approach and conformational analysis.

A novel synthetic approach toward a poorly explored bioorganometallic consisting of ferrocene-1,1'-diamine bearing structurally and chirally diverse amino acid sequences is reported. Until now, ferrocene-1,1'-diamine was suitable for accommodating only identical amino acid sequences at its N-termini, leading to the symmetrically disubstituted homochiral products stabilized through a 14-membered intramolecular hydrogen-bonded ring as is seen in antiparallel ß-sheet peptides. The key step of the novel synthetic pathway is the transformation of Ac-Ala-NH-Fn-COOH (5) (Fn = 1,1'-ferrocenylene) to orthogonally protected Ac-Ala-NH-Fn-NHBoc (7). The spectroscopic analysis (IR, NMR, CD) of the novel compounds, corroborated with DFT studies, suggests the interesting feature of the ferrocene-1,1'-diamine scaffold. The same hydrogen-bonding pattern, i.e. a 14-membered hydrogen-bonded ring, was determined both in solution and in the solid state, thus making them promising, yet simple scaffolds capable of mimicking ß-sheet peptides. In vitro screening of potential anticancer activity in Hep G2 human liver carcinoma cells and Hs 578 T human breast cancer cells revealed a cytotoxic pattern for novel compounds (150-500 µM) with significantly decreased cell proliferation.

The first ferrocene analogues of muramyldipeptide.

The two structurally interesting bioorganometallic analogues of muramyldipeptide (MDP) with potential immunomodulatory activity were synthesized starting from the O-protected N-acetylmuramic acid (MurNAc), L- or D-Ala and 1'-aminoferrocene-1-carboxylic acid (Fca). They were fully characterized by IR, (1)H NMR, (13)C NMR and CD spectroscopy as well as by FD mass spectrometry.