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

Abstract

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 β-sheet peptides. The key step of the novel synthetic pathway is the transformation of Ac–Ala––Fn–OH (5) (Fn = 1,1′-ferrocenylene) to orthogonally protected Ac–Ala––Fn–Boc (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 β-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.