Synthesis and Structural Analysis of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-­tetraazidoethylacetic Acid (DOTAZA) Complexes

Herein, we present the synthesis and structural analysis of metal complexes of enantiomerically pure 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraazidoethylacetic acid (DOTAZA). DOTAZA is a new tunable analog of DOTA, a clinically approved chelator for various pharmaceutically relevant metal ions. In this work, we investigate the complexation chemistry of DOTAZA and report the crystal structures of a number of complexes with pharmaceutically relevant metal ions such as Gd3+ [magnetic resonance imaging (MRI)], Eu3+ (luminescence spectroscopy), Y3+ [positron emission tomography (PET)], In3+ [single‐photon‐emission computed tomography (SPECT)], and Na+. These structures provide useful information for imaging applications and demonstrate the potential of DOTAZA to form stable complexes. Owing to its clickable azide functionalities, it may be used for the development of tailored imaging reagents that retain the positive complexation chemistry of the parent compound DOTA. We report the synthesis of two enantiomers of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraazidoethylacetic acid (DOTAZA), a modular DOTA derivative that allows for fine tuning of its pharmacokinetic properties for imaging applications by click chemistry. Metal complexes of DOTAZA are analyzed by NMR spectroscopy, X‐ray diffraction, and DFT calculations.