Synthesis of Novel N-Substituted Polyamide Porphyrins and Characterization of Ruthenium Complexes and Hemiporphyrazines as Potential G-quadruplex Stabilizers
Date of Award
© 2014 Michelle N. Ferreira. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.
Bachelor of Arts
Chemistry & Biochemistry
Liliya A. Yatsunyk
The primary goal of this work was to synthesize and characterize potential G-quadruplex (GQ) ligands. This thesis is divided into three parts: a synthesis section dedicated to creating new porphyrin GQ stabilizers and two characterization sections dedicated to in-depth screening and assessment of the GQ-binding properties of two classes of molecules, ruthenium complexes and hemiporphyrazines. The synthesis section aimed to modify the porphyrin N-methyl mesoporphyrin IX (NMM), which is a very selective GQ binder, with amides at its periphery in hopes of improving its GQ binding affinity while maintaining its selectivity. Seven new amide derivatives were prepared. As NMM's high GQ selectivity is mostly due to its N-methyl group, the synthesis of other N-modified porphyrins was also attempted but was largely unsuccessful. The second section of this thesis aimed to investigate the abilities of hexacoordinate ruthenium complexes to bind GQs. The interactions of these complexes with GQs have been previously characterized by past members of our lab by UV/Vis titrations, Job plots, and fluorescence titrations, and we sought to answer lingering questions about the complexes' binding stoichiometries to Tel22 as well as how they affected GQ conformations upon binding. We were able to determine that most Ru complexes bound GQs in a 1:1 and 2:1 stoichiometry, with several binding in a 3:1 stoichiometry. We were also able to determine that most of the Ru complexes did induce some conformational change in the GQ upon binding, although the exact nature of this change was not obvious. Finally, we screened a set of hemiporphyrazines and related molecules for their abilities to stabilize GQ structures, as this class of molecules has not been previously studied with GQ DNA. One molecule, cyclohexylcyanine, emerged as a very selective and promising GQ stabilizer. We hope to use the insights gained from these experiments to establish the structural basis for a ligand's selectivity and GQ-stabilizing properties in order to inform the targeted synthesis of novel GQ ligands.
Ferreira, Michelle N. , '14, "Synthesis of Novel N-Substituted Polyamide Porphyrins and Characterization of Ruthenium Complexes and Hemiporphyrazines as Potential G-quadruplex Stabilizers" (2014). Senior Theses, Projects, and Awards. 212.