ALTERATION OF ELECTRONIC RELAXATION IN MR CONTRAST AGENTS THROUGH DE-NOVO LIGAND DESIGN

The longitudinal electronic state lifetime of the paramagnetic Gd meta l within a macrocyclic ligand core can be increased by designing ligan d frames that alter the vibronic interactions between the ligating ato ms and the metal. We conducted the first pulsed EPR studies that demon strated the increase in the longitudinal state lifetimes of the electr onic subsystem at cryogenic temperatures. We also designed a simple su crose/water model that significantly increases the rotational correlat ion time in solution of the Gd chelate. This model system enables rela xivity studies at ambient temperatures that more readily interrogate e xchange and electronic contributions to the inner-sphere relaxivity by effectively removing the rotational correlation time contribution. Th ese results combined with water residence (Q) measurements suggest tha t rigidification of the macrocyclic core or that of the pendent arms i ncreases the longitudinal electronic state lifetime of the paramagneti c Gd metal. This increased lifetime possibly contributes to the improv ed relaxivity for the rigid Gd chelates observed in the sucrose/water model studies.