Lipari-Szabo approach as a tool for the analysis of macromolecular gadolinium(III)-based MRI contrast agents illustrated by the [Gd(EGTA-BA-(CH2)12)]nn+ polymer

The parameters governing the water proton relaxivity of the [Gd(EGTA-BA-(CH2)(12))](n)(n+) polymeric complex were determined through global analysis of O-17 NMR, EPR and nuclear magnetic relaxation dispersion (NMRD) data [EGTA-BA(2-)=3,12-bis(carbamoylmethyl)-6,9-dioxa-3,12-diazatetradecanedioate(2-)]. The Lipari-Szabo approach that distinguishes the global motion of the polymer (tau (g)) from the local motion of the Gd(III)-water vector (tau (1)) was necessary to describe the H-1 and O-17 longitudinal relaxation rates: therefore for the first time it was included in the global simultaneous analysis of the EPR,O-17 NMR and NMRD data. The polymer consists on average of only five monomeric units, which limits the intramolecular hydrophobic interactions operating between the (CH,),, groups. Hence the global rotational correlation time is not very high (tau (298)(g)=3880+/-750ps) compared to the corresponding DTPA-BA-based polymer (about 15 monomeric units), where tau (298)(g)=6500 ps. AS a consequence, the relaxivity is limited by the rotation, which precludes the advantage obtained from the fast exchanging chelating unit (k(ex)(298)=2.2+/-0.1x10(6) s(-1)).