Date of Award

Spring 2009

Project Type


Program or Major


Degree Name

Doctor of Philosophy

First Advisor

Gary R Weisman


The development of nitrogen-protecting groups that are orthogonal to the N-benzyl group for use in cross-bridged tetraazamacrocycles and the synthesis and complexation of bridged bis-tetraazamacrocycles are presented. The allyl, p-methoxybenzyl (PMB), and 2-naphthylmethyl (Nap) nitrogen-protecting groups were investigated for use on cross-bridged tetraazamacrocycle systems and conditions for deprotection were found for the N-allyl and N-PMB protecting groups. The conditions applied for the cleavage of the N-allyl and N-PMB groups and the systems that these conditions were employed on are illustrated below. This research has demonstrated that the N-allyl and N-PMB protecting groups are applicable to a variety of systems. These protecting groups have the potential to be utilized in the synthesis of novel cross-bridged bis-tetraazamacrocycles where the N-benzyl protecting group may not be applicable. These cross-bridged systems can be further functionalized, in particular the mono-benzyl cross-bridged cyclam system 33, for a variety of biomedical purposes including positron emission tomography (PET) imaging.

The N-allyl protecting group was also used to synthesize a cross-bridged bis-cyclen 31 that can now be further functionalized for a variety of biomedical purposes. Copper (II) and zinc (II) complexes of 94a and 90 and the diamide cross-bridged bis-tehaazamacrocycle 105 were also synthesized. These bis-tetraazamacrocycle systems may find use as potential anti-HIV agents or for stem-cell mobilization.