A Class of FeIII Macrocyclic Complexes with Alcohol Donor Groups as Effective T1 MRI Contrast Agents

Early studies suggested that Fe^III complexes cannot compete with Gd^III complexes as T₁ MRI contrast agents. Now it is shown that one member of a class of high‐spin macrocyclic Fe^III complexes produces more intense contrast in mice kidneys and liver at 30 minutes post‐injection than does a commercially used Gd^III agent and also produces similar T₁ relaxivity in serum phantoms at 4.7 T and 37 °C. Comparison of four different Fe^III macrocyclic complexes elucidates the factors that contribute to relaxivity in vivo including solution speciation. Variable‐temperature ¹⁷O NMR studies suggest that none of the complexes has a single, integral inner‐sphere water that exchanges rapidly on the NMR timescale. MRI studies in mice show large in vivo differences of three of the Fe^III complexes that correspond, in part, to their r₁ relaxivity in phantoms. Changes in overall charge of the complex modulate contrast enhancement, especially of the kidneys.