Effect of Magnetic Coupling on Water Proton Relaxivity in a Series of Transition Metal GdIII Complexes

A fundamental challenge in the design of bioresponsive (or bioactivated) GdIII-based magnetic resonance (MR) imaging probes is the considerable background signal present in the “preactivated” state that arises from outer-sphere relaxation processes. When sufficient concentrations of a bioresponsive agent are present (i.e., a detectable signal in the image), the inner- and outer-sphere contributions to r1 may be misinterpreted to conclude that the agent has been activated, when it has not. Of the several parameters that determine the observed MR signal of an agent, only the electron relaxation time (T1e) impacts both the inner- and outer-sphere relaxation. Therefore, strategies to minimize this background signal must be developed to create a near zero-background (or truly “off” state) of the agent. Here, we demonstrate that intramolecular magnetic exchange coupling when GdIII is coupled to a paramagnetic transition metal provides a means to overcome the contribution of second- and outer-sphere contribution...