Developing NMR and Visible Spectroscopy Methods to Determine PKa’s of Glycine Metal Complexes

Abstract

Peptidomimetics offers the potential of drug design using small peptide sequences designed to mimic the tertiary structure of a large protein to act as a pharmacophore in the active site. Unnatural amino acids are often used to create tertiary structural features in small peptide mimetics, yet, synthesizing unnatural amino acids still remains a challenge. The use of electron withdrawing groups is a well-known approach to change the chemical properties of a molecule, including the acidity. Our project's goal is to quantify the changes in pKa of previously synthesized ligands with the presence or absence of electron withdrawing groups attached to the molecule in organic solvents. Challenges in determining the pKa’s of these ligands include monitoring the equilibrium of a weak acid-weak base chemical reaction and the use of different methods in determining the acidity of a proton in organic solvent conditions, since common aqueous methods do not apply in organic solvent. Therefore, we are applying proton nuclear magnetic resonance (1H-NMR) and visible spectroscopy as means to monitoring the weak acid-weak base interaction and to quantify the pKa by proton integration and wavelength absorbance changes, respectively.