Date of Award

Winter 2008

Project Type


Program or Major


Degree Name

Doctor of Philosophy

First Advisor

Gary Weisman


The synthesis of a variety of cross-bridged tetraazamacrocycles bearing phosphonate pendant arms and their corresponding phosphonic acid derivatives as well as their Cu(II) complexes are presented. The half-life of decomplexation of Cu(II)·51 in 5M HCl at 90°C was found to be 3.8 hours. Ligand 51 showed faster complexation kinetics relative to known cross-bridged tetraazamacrocycles bearing ionizable pendant arms. The biodistribution of 64Cu(II)·51 was studied in male rats and indicated an improved blood and liver clearance and higher bone retention of 64Cu(II)·51 relative to 64Cu(II)·10.*.

The formation of a single pendant-armed cross-bridged cyclam is presented through an unusual single alkylation of cross-bridged cyclam. Several experiments were implemented to probe the origin of the selectivity of the reaction including computational studies, 1D 1H NMR and 2D NMR experiments. Monoamide ligand 64 was used as a springboard for the formation of several unsymmetrical pendant-armed cross-bridged cyclams.*.

Attempts were made toward the synthesis of two potential bifunctional chelators for radiopharmaceuticals, each bearing only one phosphonic acid pendant arm and one free carboxylate for conjugation to somatostatin analogues.*.