Solution Structure and Relaxivity of Ln‐DOTXAZA Derivatives

Abstract Herein we report the synthesis and structural analysis of tunable 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA)‐derivatives bearing azidoethyl side chains. According to number chains, compounds are termed DOTXAZA (with X=1–4). All derivatives retain well‐approved DOTA scaffold for metal complexation with 8 coordinating functionalities applicable Cu‐catalyzed alkyne‐azide cycloaddition (CuAAC). They may thus be used assemble new Gd‐based contrast agents (GBCAs) tailored pharmacokinetic or MRI properties retaining high stability clinically DOTA‐derived GBCAs. The complex geometry all was investigated in solution NMR‐spectroscopy corresponding Eu‐complexes. A correlation longitudinal relaxivity Gd‐complexes revealed an increase increasing substitution series. Moreover, CuAAC‐modified DOTAZA‐derivatives neutral, charged, zwitterionic groups were prepared. Although similar molecular mass, pronounced differences relaxivities from r 1 =3.9–7.9 m −1 s water at 1.5 T 37 °C. Relaxivities these complexes found strongly dependent on chain charge most likely determined by second‐sphere effects.