Alteration of electronic relaxation in MR contrast agents through de-novo ligand design.

The longitudinal electronic state lifetime of the paramagnetic Gd metal within a macrocyclic ligand core can be increased by designing ligand frames that alter the vibronic interactions between the ligating atoms and the metal. We conducted the first pulsed EPR studies that demonstrated the increase in the longitudinal state lifetimes of the electronic subsystem at cryogenic temperatures. We also designed a simple sucrose/ water model that significantly increases the rotational correlation time in solution of the Gd chelate. This model system enables relaxivity studies at ambient temperatures that more readily interrogate exchange and electronic contributions to the inner-sphere relaxivity by effectively removing the rotational correlation time contribution. These results combined with water residence (Q) measurements suggest that rigidification of the macrocyclic core or that of the pendant arms increases the longitudinal electronic state lifetime of the paramagnetic Gd metal. This increased lifetime possibly contributes to the improved relaxivity for the rigid Gd chelates observed in the sucrose/ water model studies.