A Janus Chelator Enables Biochemically Responsive MRI Contrast with Exceptional Dynamic Range

Abstract

We introduce a new biochemically responsive Mn-based MRI contrast agent that provides a 9-fold change in relaxivity via switching between the Mn³⁺ and Mn²⁺ oxidation states. Interchange between oxidation states is promoted by a "Janus" ligand that isomerizes between binding modes that favor Mn³⁺ or Mn²⁺. It is the only ligand that supports stable complexes of Mn³⁺ and Mn²⁺ in biological milieu. Rapid interconversion between oxidation states is mediated by peroxidase activity (oxidation) and l-cysteine (reduction). This Janus system provides a new paradigm for the design of biochemically responsive MRI contrast agents.