Primary Amine Pendant Arms Useful for Conjugation of Cross-bridged Tetraazamacrocycles to Other Bioactive Groups

Abstract

Cross-bridged tetraazamacrocycles have made important contributions as ligands that strongly bind transition metal ions. This property is very useful when the metal complex is intended for use under harsh conditions. One application that has benefited from such complexes is medical imaging, where radioactive transition metal ions can be stably bound to the cross-bridge ligand, injected into patients, and used to identify diseased tissues, such as cancerous tumors. Pendant arms can be added to the cross-bridged tetraazamacrocycle to allow conjugation to other biologically active compounds, or biomolecules such as proteins and nucleic acids themselves. The conjugated bioactive compound might perform various therapeutic activities, while the cross-bridged tetraazamacrocyle metal complex attached serves as an imaging agent to help illuminate the biological effect of its conjugated partner. In this project, we are developing the synthesis of a primary amine pendant arm to the known ethylene cross-bridged tetraazamacrocycles. This functional group is well-known for its ability to be conjugated to biomolecules. Synthetic and characterization methods and results for these novel compounds will be presented.