An Fe complex for (19)F magnetic resonance-based reversible redox sensing and multicolor imaging

We report a first-in-class responsive, pentafluorosulfanyl (–SF(5))-tagged (19)F MRI agent capable of reversibly detecting reducing environments via an Fe(II/III) redox couple. In the Fe(III) form, the agent displays no (19)F MR signal due to paramagnetic relaxation enhancement-induced signal broadening; however, upon rapid reduction to Fe(II) with one equivalent of cysteine, the agent displays a robust (19)F signal. Successive oxidation and reduction studies validate the reversibility of the agent. The –SF(5) tag in this agent enables ‘multicolor imaging’ in conjunction with sensors containing alternative fluorinated tags and this was demonstrated via simultaneous monitoring of the (19)F MR signal of this –SF(5) agent and a hypoxia-responsive agent containing a –CF(3) group.