Date of Award

Spring 5-5-2021

Degree Type


Degree Name

PhD. Chemistry


Chemistry and Biochemistry


Stephen p. Kelty, Ph.D.

Committee Member

Cecilia Marzabadi, Ph.D.

Committee Member

James Hanson, Ph.D.


Modified Proline, Cis-Trans Equilibrium, DFT, MMMD, Phthalonitriles


Proline is a unique amino acid because it is the only amino acid whose side chain wraps around and bonds back to the peptide backbone. This ring shape helps proteins form conformations which would otherwise not be possible such as hairpin turns. The cis/trans isomerization of the peptide bond between the preceding amino acid (Xaa) and Proline is important in determining how the secondary structure folds. Thus, being able to control the cis/trans isomerization is important when a specific conformation is desired; Proline can be modified to get make the equilibrium shift whichever way is needed. The modifications can influence the sterics, electronic structure, or both to achieve the desired results.

In chapter 1 of this work, a suite of Proline derivatives was examined using density functional theory to acquire the difference in total energy between the cis and trans conformations of the peptide bond. Both steric and electronic interactions were considered to see where the stability of the dominant conformation was coming from. In chapter 2 the equilibrium structures were used to create a CHarMM force field to then be calculated in a molecular dynamics simulation. The simulations were of a 5-mer polypeptide FGXFG, where X was either regular proline or a proline derivative. The objective of this simulation was to see how far apart the ends of the poly peptide were and how often. This is of interest because when trying to create a cyclic peptide, having the ends closer together for a longer period promotes cyclization. This could speed up reaction times as well as reducing waste in the form of linear chains

Chapter 3 focuses on a class of molecules called phthalonitriles. These molecules are of synthetic interest in making larger macrocycles named phthalocyanines. Different variations of phthalonitriles can be used to then change the properties, in this case, the iso-C3F7 groups were indented mainly to help mitigate aggregation of the macrocycles in solution. The computational information presented here is matched up with the experimental for classification of the newly synthesized phthalonitriles. Geometry optimizations with all possible rotamers were performed to get the global minimum for each molecule. After the global minimum was found for each molecule, both the IR and UV-Vis spectra were predicted using B3LYP/6-311++G**. The calculated data assisted in the classifications of this class of molecules.