A 1H Relaxometric Approach to Understanding the Solution Speciation of Paramagnetic Complexes

The characterization of solution speciation of Mn(II) complexes remains a major hurdle in the development of safe and effective Mn(II)-based MRI contrast agents. A 1H relaxometric technique has been developed which provides accurate concentrations of [Mn(H2O)6]2+ from the ratios of longitudinal to transverse 1H relaxation times (T1p/T2p ratios) of the aqueous solvent for a variety of Mn(II) complexes. pH-dependent T1p/T2p ratio data were fit to a general equilibrium expression to determine the formation constants of the complexes. The results of this analysis agree with the results of potentiometry, the primary technique employed to determine solution speciation, demonstrating the utility of this ratiometric analysis for quantitating thermodynamic stability of Mn(II) complexes. The T1p/T2p ratio analysis was used to determine the previously unknown formation constant for [Mn(DOTAM)]2+, a complex that is challenging to characterize through standard potentiometric titration techniques. The relaxometric protocol developed herein may be used in conjunction with potentiometric titrations to elucidate the appropriate model of solution speciation for Mn(II) complexes. General requirements (e.g., magnetic field limitations, molecular constraints, etc.) of this technique are also addressed.

The large difference in T1p/T2p ratios of Mn(II) complexes and [Mn(H2O)6]2+ have been rationalized using Solomon-Bloembergen-Morgan paramagnetic relaxation theory. This analysis has been extended to several first row transition metal aqua ions and the Gd(III) aqua ion. Cubic electronic symmetry is likely a requirement for Mn(II) systems to have T1p/T2p ratios >2. A long electronic relaxation rate and a large 1H hyperfine coupling constant are the general requirements to observe a T1p/T2p ratio >2 for a solution containing paramagnetic aqua ions.