Interaction of ferrocenoyl-dipeptides with 3-aminopyrazole derivatives: beta-sheet models? A synthetic, spectroscopic, structural, and electrochemical study

The use of 3-aminopyrazole derivatives as P-sheet templates is investigated using a series of ferrocenoyl (Fc)dipeptides (Fc-Gly(2)-OEt, Fc-Ala(2),-OB zl, Fc-Leu-Phe-OMe, Fc-Val-Phe-OMe, Fc-Phe(2)-OMe, Fc-Leu(2)-OMe, Fe-Val(2) -OMe). The synthesis and full characterization are reported. The solid-stat e structures of Fc-Gly(2)-OMe and Fc-Leu-Phe-OMe show extensive hydrogen bo nding of the podand peptide substituents, resulting in the formation of sup ramolecular Fc-dipeptide assemblies. For Fc-Gly(2)-OMe, this can be describ ed as a parallel beta -sheet, whereas intermolecular interactions in Fc-Leu -Phe-OMe result in the formation of supramolecular helical structures. The saturation titrations- of Fc-dipeptides with 3-aniino-5-methylpyrazole (3-A MP) and 3-trifluoroacetylamido-5-methylpyrazole (3 -TFAc-AMP) show a 1: 1, interaction of the Fc-peptide with the aminopyrazole derivatives. IR measur ements in solution confirm binding to the top face of the Fc-dipeptide and the involvement of the Fc-C=O and the ester C=O groups in establishing H-bo nding interactions with the 3-TFAc-AMP. However, binding constants in chlor oform are low and range from 8 to 27 M-1, which correspond to binding energ ies of 5-7 kJ mol(-1). In higher polarity. solvents, such as acetonitrile o r acetone, the binding constants are below 5 M-1 emphasizing the limited ut ility of 3-AMP derivatives as P-sheet templates. Electrochemical measuremen ts confirm the weak interactions between the various Fc-dipeptides and 3-TF Ac-AMP. Typical shifts in the. redox potential of the Fe moiety, are in the range 0-20 mV. Attempts to modify 3 AMP at the 3-position by carbodiimide coupling with amino acid derivatives and, thus, enhance the binding to the Fe-peptide resulted in 2-arr ino acid substituted 3-AMP derivatives. Substi tution at the 2-position blocks the binding site, and no interactions with Fc-dipeptides are observed.