The principal objective of this project was to obtain an understanding of the fundamental coordination chemistry of polyaminocarboxylate ligands which have had one or more carboxylates replaced with a phenolate metal binding site. Thus, synthesis of a series of novel acyclic ligands of various substitution patterns was required. Information acquired from evaluation of the solution chemistry of these compounds, their kinetic and thermodynamic properties, and their serum stability have been employed to gauge the potential usefulness of the complexes in vivo. These studies have provided a basis for rational design of bifunctional ligands for complexing metals useful as cytocidal or diagnostic agents. Results of the above studies have indicated that in and of themselves, the ortho-hydroxybenzyl metal binding site, when incorporated into a polyaminocarboxylate ligand, does not provide an adequately stable complex in vivo. However, the knowledge gained from the syntheses provides rational synthetic routes to analogous thiophenolic type ligands and as such, this project will be incorporated into project number Z0l CM 06399- 03 RO.
