1′-Acetylferrocene amino acid esters and amides. A simple model for parallel β-helical peptides

Abstract

In this study we present a synthesis and conformational analysis of 1′-acetylferrocene amino acid derivatives of type Ac–Fn–CO–AA–Y (Fn=ferrocene-1,1-diyl; AA=Gly, Ala or Val; Y=OMe or NHMe) as a simple model for parallel β-helical peptides. Derivatives with only one amino acid adopt a reduced number of total conformations and allow a more exact analysis of intramolecular hydrogen bonds (IHB) close to the ferrocene unit. Conformational analysis of these bioconjugates was performed by a combination of spectroscopic techniques (IR, NMR and CD) and corroborated by solution-phase DFT calculations. The investigation of ester conjugates 1–3 indicates the coexistence of non-bonded (an open forms) and hydrogen bonded NHa group forming a 7-membered ring (γ-turn). The amide derivatives 4–6 with an additional NHb hydrogen bond donor are mostly constituted of conformers with a 10-membered ring (β-turn) as a single IHB pattern or the β-turn accompanied by a 7-membered ring (γ-turn) containing NHa group. The exchange of the amino acid side-chain does not significantly affect the conformational properties and IHB pattern of the studied conjugates 1–6.