C2-Symmetric Ferrocene-Bis(ureido)peptides: Synthesis, Conformation and Solid-State Structure

The extension of peptide derivatives of ferrocene‐1,1′‐dicarboxylic acid by formal insertion of NH units between ferrocene and peptide strands results in ferrocene–bis(ureido)peptides. Experimentally, alanine and dialanine methyl esters were attached to the 1‐ and 1′‐position of 1,1′‐diisocyanoferrocene to give the corresponding bis(ureido)peptide derivatives 3 and 4. The conformation of 3 has been determined in the solid state by X‐ray crystallography. In solution the preferred conformation of 3 and 4 has been elucidated by NMR, IR and CD spectroscopy in concert with DFT calculations. The secondary structure of ferrocene–bis(ureido)peptides 3 and 4 is determined by double bifurcated intramolecular hydrogen bonds (IHBs). The different stability of the secondary structures of 3 and 4 is due to different types of IHBs. Formal NH insertion in peptidic bioconjugates of ferrocene‐1,1′‐dicarboxylic acidresults in ferrocene–bis(ureido)peptides. Conformational analyses were performed by IR, NMR and CD spectroscopy and augmented by DFT calculations. A stable intramolecular hydrogen‐bond pattern with double bifurcated intramolecular hydrogen bonds is revealed.