Synthesis and Characterization of New Cyclic and Acylic Ferrocene Peptide Conjugates

Abstract

In this thesis a series of diphenol phenanthroline (Dpp) peptide conjugates were synthesized and then coupled to ferrocene to give the corresponding organometallic conjugates. The first step of the synthesis was achieved by esterification of peptides with the phenol group of the Dpp. The next step was the removal of the protecting Boc group and the addition of ferrocene acid chloride at high dilutions to give the desired macrocycles of the type Dpp-(peptide)₂ Fc. (peptide = Leu-Leu (3), Leu-Leu-Leu (5) ). However, the syntheses proceeded in low yields where only small quantities of the desired products were obtained. A suitable crystal of compound 3 was grown from CHCl₃ which shows a number of intra and intermolecular hydrogen bonding interactions between peptides strands. In addition, the system [Dpp-Fc]₂ (1) was syntheised by refluxing Dpp and Fc[COCl]₂ in dichloromethane. A suitable crystal was grown which has π-π interactions between intramolecular Dpp units as well as a number of CH-π interactions which determine the crystal packing. The electrochemical experiments on compound 1 show a cathodic shift upon addition of Zn²⁺ to a solution of 1. This observation is believed to occur because of a conformational change in 1. The last area of synthesis that was done was the attempt at β-sheet formation using Fc as a scaffold to align peptide strands. Two systems were studied in this thesis [Fc(n’-AA-OMe)(1-AA)]₂-1,4butyl diamine. (AA =Ala (8), Gly (9)). Both were studied by ¹H NMR to evaluate the presence of hydrogen bonding interactions. The results indicate the presence of intramolecular H-bonding, which is believed to form β-sheet like structures in solution.