Exploring the synthesis and characterization of fac-Re(CO)3L complexes using diethylenetriamine derivative functionalized at the central nitrogen

Abstract

The aim of this research is to develop new rhenium complexes with favorable bio-distribution properties which can be used as radiometal complexes or for conjugation with biomolecules for the development of targeted radiolabelled biopharmaceuticals. Two metals of interest utilized in radiopharmaceuticals are technetium and rhenium, both of which share similar chemical and structural properties. The coordination chemistry of these metals is highly dependent upon ligands that are structurally and chemically robust among other factors. The synthesis of new symmetrical tridentate ligands and ligand conjugation methods will expand the likelihood of developing suitable fac-[Re(CO)3L]n compounds with promising biomedical properties and were consequently the subject of this investigation. In order to accomplish this, the design, synthesis, characterization and X-ray structure of new water-soluble rhenium complexes for assessing metal binding to biomolecules were investigated. Three diethylenetriamine (dien) derivatives, 2-(bis(2-aminoethyl)amino)-N-(2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl)acetamide (atfcdien, 3), 2-(bis(2-aminoethyl)amino)-N-(3,5-bis(trifluoromethyl)benzyl)acetamide (tfmedien, 6), and N-benzyl-2-(bis(2-aminomethyl)amino)acetamide (badien, 9) and their rhenium complexes were synthesized. 1H NMR spectroscopy, mass spectrometry and X-ray crystallography techniques were employed to characterize the ligands and their rhenium complexes [Re(CO)3atfcdien]Br (10), [Re(CO)3tfmedien]Br (11) and [Re(CO)3badien]Br (12). 1H NMR studies were conducted to examine chelated Re complexes revealed a consistent downfield shift of the CH signal of the dien moiety for all three new ligands.