Spectroscopic and Electrochemical Studies of Ferrocenyl Triazole Amino Acid and Peptide Bioconjugates Synthesized by Click Chemistry

Ferrocenyl triazole amino acid (l-leucine methyl ester (2, 5), l-phenylalanine methyl ester (3, 7), l-alanine methyl ester (4), l-valine tert-butyl ester (6), l-proline methyl ester (8)) and peptide derivatives ([Leu5]-enkephalin (9, 10)) were prepared by Cu(I)-catalyzed [3+2] cycloaddition of azidoferrocene and 1,1′-diazidoferrocene with the corresponding alkyne-modified amino acids and peptide. A purity of >95% for the peptide conjugates was confirmed by HPLC. All new compounds were comprehensively characterized by elemental analysis, mass spectrometry (FAB and ESI-MS, including high-resolution MS), IR, and multinuclear 1D and 2D NMR spectroscopy. Solution structures were studied by circular dichroism (CD) and NMR spectroscopy, showing that compounds 5, 6, and 7 form intramolecular hydrogen bonds (IHBs) in noncoordinating solvents. Electrochemical studies show reversible processes of the redox couple Fc0/Fc+ (Fc = ferrocenyl) for compounds 2−9, whereas compound 10 exhibits an irreversible oxidation. A g...