| Abstract | The Green research group has developed a library of tetraaza macrocyclic ligands with the potential to treat neurodegenerative diseases by binding free metals, scavenging radicals, and reducing oxidative stress. The copper complex of one of these ligands, OHPyN3Cu, was discovered to form a novel helix structure upon crystallization around pH 6.5. To understand the mechanism and driving forces that led to formation of this helix, we investigated several aspects of the ligand. Density-functional Theory (DFT) studies, a comparison of keto/enol tautomerization stability, and a comparison of bond lengths, were considered to determine the protonation state of the pyridol moiety and, therefore, the character of the bond between the subunits of the helix. We also considered other structural aspects of Cu1H including the interactions with perchlorate counterions and the symmetry of Cu1H. Because Cu1H does not exhibit the typical factors that stabilize the formation of helices, such as intrastrand hydrogen bonding or pi stacking, we conclude that perchlorate templating through hydrogen bonding between perchlorate counterions and Cu1H is the primary driving factor of helix formation. The discovery of this helix structure further highlights the diversity of inorganic metallohelices and demonstrates the importance of tautomerization and pH, as well as counterions in designing drugs and other molecules. |
