AbstractTwo mononuclear ferric complexes are reported that respond to a pH change with a 27‐ and 71‐fold jump, respectively, in their capacity to accelerate the longitudinal relaxation rate of water‐hydrogen nuclei, and this starting from a negligible base value of only 0.06. This unprecedented performance bodes well for tackling the sensitivity issues hampering the development of Molecular MRI. The two chelates also excel in the fully reversible and fatigue‐less nature of this phenomenon. The structural reasons for this performance reside in the macrocyclic nature of the hexa‐dentate ligand, as well as the presence of a single pendant arm displaying a five‐membered lactam or carbamate which show (perturbed) pK_a values of 3.5 in the context of this N6 N5O1 coordination motif.