Synthesis and Relaxation Properties of Three Novel Bis-macrocycles: Attempt towards Calcium Sensitive MRI Contrast Agents

MR contrast agents whose efficiency depends on the concentration of signaling molecules may be used to directly visualize neuronal activation. The so-called ‘smart’ contrast agents for magnetic resonance imaging exhibit dynamic and reversible modulation of their relaxivity by specific physiological or biochemical triggers such as changes in pH, Ca2+ concentration or enzymatic activity. The extracellular concentration of Ca2+ plays an important role in the physiological and pathological processes of the nervous system; it led us to design chelating systems in which the relaxivity is influenced by the Ca2+ concentration. We synthesized three novel bifunctional bismacrocycles based on DO3A-EA coupled to EDTA/DTPA-bisanhydride via amide bonds