Synthesis and Conformational Study of Bioconjugates Derived from 1-Acetyl-1'-aminoferrocene and [alpha]-Amino Acids

1,1'-Disubstituted ferrocene conjugates present useful and efficient bioorganometallic constraint design to reduce the conformational flexibility of small peptides. In this study we present the first systematic conformational analysis of nonsymmetric ferrocene peptidomimetics (Boc-AA-NH-Fn-COMe; Boc = tert-butoxycarbonyl; AA = Gly, L-Ala, L-Val; Fn = 1,1'-ferrocenylene) and their monosubstituted analogues (Boc-AA-NH-Fc; Fc = ferrocenyl; AA = Gly, L-Ala, L-Val). The spectroscopic data (IR, NMR and CD) were corroborated by DFT calculations and indicated the engagement of the NH group closest to the ferrocene unit in intrachain hydrogen bonds. This medium-strength bond is not disrupted by the introduction of a hydrogen-bonding acceptor on the other ferrocene ring, but rather is accompanied by an additional interchain hydrogen bond, which causes the restricted rotation of ferrocene rings and gives rise to a chiral arrangement of the ferrocene core in a P helical manner.