Organometallic beta-turn mimetics. A structural and spectroscopic study of inter-strand hydrogen bonding in ferrocene and cobaltocenium conjugates of amino acids and dipeptides

By using organometallic turn-mimetics, we have investigated the influence of a positive charge on the structure and stability of peptide turn structures which are stabilized by hydrogen bonds. Starting from metallocene mono- (1) or di-carboxylic acid (2), 11 amide derivatives were prepared, namely CpMC5H4-CO-Phe-OMe (3), CpMC5H4-CO-Ala-Phe-OMe (4), CpMC5H4-CO-NH-CH(CH3)-Ph (5), M(C5H4-CO-Phe-OMe)2(6), M(C5H4-CO-Ala-Phe-OMe)2(7), and Fe(C5H4-CO-NH-CH(CH3)-Ph)2(8a) with Cp =eta-C5H5 and M = Fe (ferrocene, a) or M = Co+(cobaltocenium, b). All compounds were characterized by elemental analysis, MS, IR, electrochemistry, M?ssbauer spectroscopy (a only) and NMR spectroscopy. Solid state structures of 4a, 6a, 7a, 3b, and 5b were determined by single crystal X-ray diffraction. 1H NMR data (NH) and delta(NH) with T) as well as solution IR spectra were evaluated in order to determine intramolecular hydrogen bond interactions in solution. No intramolecular hydrogen bonds form in the monosubstituted derivatives 3–5 and in 8a. For 7, a strong intramolecular hydrogen bond is observed between the NHAla and COAlaʹ of the other ring, forming an 11-membered ring in solution as well as in the solid state. The situation is most complex for 6, which forms an intramolecular 8-membered ring by hydrogen bonds NHPheCOCp in the solid state (6a), but a symmetrical 11-membered ring structure with NHPheCOPheʹ bonds in solution. A comparison of the uncharged ferrocene derivatives with the iso-structural but positively charged cobaltocenium derivatives reveals only minor differences. Apparently, the presence of a positive charge does not significantly influence hydrogen bonds in peptide turn structures. Our results are related to geometries and amino acid sequences in protein turn structures and a nomenclature for turn mimetics with a parallel orientation of the two peptide strands is proposed.