Phenols as Diamagnetic T 2 ‐Exchange Magnetic Resonance Imaging Contrast Agents

Although T 2 ‐exchange ( T 2ex ) NMR phenomena have been known for decades, there has been a resurgence of interest to develop T 2ex MRI contrast agents. One indispensable advantage of T 2ex MR agents is the possibility of using non‐toxic and/or bio‐compatible diamagnetic compounds with intermediate exchangeable protons. Herein a library of phenol‐based compounds is screened and their T 2ex contrast (exchange relaxivity, r 2ex ) at 9.4 T determined. The T 2ex contrast of phenol protons allows direct detection by MRI at a millimolar concentration level. The effect of chemical modification of the phenol on the T 2ex MRI contrast through modulation of exchange rate and chemical shift was also studied and provides a guideline for use of endogenous and exogenous phenols for T 2ex MRI contrast. As a proof‐of‐principle application, phenol T 2ex contrast can be used to detect enzyme activity in a tyrosinase‐catalyzed catechol oxidation reaction.