Phenols as Diamagnetic T2 -Exchange Magnetic Resonance Imaging Contrast Agents.

Although T2 -exchange (T2ex ) NMR phenomena have been known for decades, there has been a resurgence of interest to develop T2ex MRI contrast agents. One indispensable advantage of T2ex 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 T2ex contrast (exchange relaxivity, r2ex ) at 9.4 T determined. The T2ex contrast of phenol protons allows direct detection by MRI at a millimolar concentration level. The effect of chemical modification of the phenol on the T2ex 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 T2ex MRI contrast. As a proof-of-principle application, phenol T2ex contrast can be used to detect enzyme activity in a tyrosinase-catalyzed catechol oxidation reaction.