Date of Award
Master of Science
Dr. Heinz-Bemhard Kraatz
Ferrocene peptide conjugate foldamers have been extensively studied as models of protein secondary structures. Particularly, disubstituted ferrocene derivatives such as ferrocene dicarboxylic acid (4), ferrocene diamine (5) and 1-aminoferrocene-l’-carboxylic acid (6) are important in the design ofpeptide mimics. The inter-ring spacing between two cyclopentadienyl (Cp) rings in ferrocene is appropriate for forming hydrogen bonding between podant peptide chains attached to the two Cp rings, which is of great importance for the formation of stable supramolecular structures. These bioconjugates may enhance our understanding of peptide and protein folding, which may lead to the design o f new bioactive molecules. Comparing the three disubstituted ferrocene models, there are very few studies o f the peptide conjugates of ferrocene diamine. This work focuses on the preparation and hydrogen bonding studies of ferrocene diamine peptide conjugates in solution and in the solid state. The chiral dipeptide sequences Boc-Ala-Pro-OH and Boc-Ala-Pro-OH
\ were introduced to the ferrocene diamine scaffold by peptide coupling procedures.
The following conjugates were synthesized: Fc[NH-L-Pro-L-Ala-Boc]2 (44), Fc[NH-D-Pro-D-Ala-Boc]2 (45), Fc[NH-L-Pro-D-Ala-Boc]2 (46), Fc[NH-D-Pro-L-Ala- Boc]2 (47), Fc[NH-L-Ala-L-Pro-Boc]2 (50), Fc[NH-D-Ala-D-Pro-Boc]2 (51), Fc[NH- L-Ala-D-Pro-Boc]2 (52), Fc[NH-D-Ala-L-Pro-Boc]2 (53). The attached peptide chains induce axial chirality into the ferrocene group as expected. The axial chirality o f the ferrocene group is dependent on the proximal amino acid and was studied by circular
dichroism (CD) spectroscopy. In all structures, helicity is induced by the proximal in
amino acid. L-amino acid results in P-helicity, while D-amino acid results in M-helicity of ferrocene group. Hydrogen bonding interactions were observed in these systems by ‘H-NMR and IR spectroscopies. Furthermore, pyridine group was coupled to these ferrrocene peptide conjugates to study the metal coordination in these systems by 'H-NMR, IR and MS spectroscopies. The following pyridine conjugates Fc[NH-L-Pro-L-Ala-Py]2 (48) and Fc[NH-D-Pro-D-Ala-Py]2 (49) were synthesized to study metal coordinaton and its effects on the axial chirality by circular dichroism spectroscopy. A range of metal ions were found to form the 1:1 complexes with the ferrocene peptide conjugates 48-49. In these systems, the ferrocene group maintains its P-helicity in solution
Shen, Yunying, "SYNTHESES AND HYDROGEN BONDING STUDIES OF NEW FERROCENE DIAMINE PEPTIDE CONJUGATES" (2011). Digitized Theses. 3554.