Improved Redox-Responsive Cobalt(II) ¹⁹F Magnetic Resonance Imaging Agents through Addition of Hydrogen Bond Donors

Redox regulation through reactive oxygen species (ROS) is an essential component of the inflammatory response. ROS can be sensed by ¹⁹F magnetic resonance spectroscopy and imaging using redox-active cobalt macrocycles with an appended fluorine tag. The sensitivity of these cobalt complexes was investigated by altering the identity of the oxygen donor (hydroxypropyl, carboxylate, dimethyl amide, and acetamide) attached to the triazacyclononane scaffold. A distinct shift in the ¹⁹F MR frequency between the Co²⁺ and Co³⁺ states (6-10 ppm) allows for robust imaging of the probes before and after oxidation using selective pulse sequences. Of these complexes, <b>[Co(II)HP]</b>^<b>2+</b> exhibited an enhanced sensitivity to ROS when comparing burst kinetics and steady state oxidation through the glucose oxidase enzyme (GOX). This sensitivity corresponded with an increased fractional <i>q</i> value and enhanced interactions between Co²⁺ and ¹⁷O nuclei, which are indicative of a strong hydrogen bonding network in the secondary coordination sphere.