Phenols as Diamagnetic T₂ -Exchange Magnetic Resonance Imaging Contrast Agents

Although T₂ -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.