Zn(II)-Responsive\nMRI Probe Based on an Fe(III) Macrocyclic\nComplex

The development of responsive MRI contrast agents to\ndetect fluctuations\nin Zn(II) is a growing area of research. Here we describe a high-spin\nFe(III) coordination complex, Fe(ADAPT), as one of the first examples\nof an Fe(III) MRI probe that is responsive to Zn(II). The six-coordinate\nFe(ADAPT) contains a phenolate-appended 1,4,7-triazacyclononane (TACN)\nligand framework, with the phenolate groups linked to a Zn(II) binding\nmoiety. Fe(ADAPT) lacks an exchangeable inner-sphere water and thus\nrelies on second- and outer-sphere water interactions for proton relaxation.\nFe(ADAPT) is highly kinetically inert under physiological conditions\nat pH 7.4 and 37 °C and to excess Zn(II) over 72 h. In the presence\nof 2 equiv of Zn(II) with a 200 μM Fe(III) probe, an increase\nin relaxivity of ∼80% is observed. A ternary complex among\nFe(ADAPT), Zn(II), and human serum albumin leads to a nearly 200%\nincrease in relaxivity.