Relaxivity and Water Exchange Studies of a Cationic Macrocyclic Gadolinium(III) Complex

Abstract

We conducted relaxometric and water exchange studies of the cationic [Gd((S,S,S,S)-THP)(H2O)]3+ complex (THP 1,4,7,10-tetrakis(2-hydroxy-propyl)-1,4,7,10-tetraazacyclododecane). While the NMRD profiles obtained are typical for DOTA-like complexes (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate), variable-temperature 7O NMR investigations revealed a relatively high water exchange rate (k(298)(ex) = 1.89 x 10(7) s(-1)). These results differ from those reported for other cationic tetraamide macrocyclic Gd(III) complexes, which exhibit characteristically low exchange rates. Since the low exchange rates are attributed partially to the geometry of the M isomer (square antiprismatic) in the tetraamide derivatives, the atypical water exchange rate observed in [Gd((S,S,S,S)-THP-(H2O)]3+ may result from a twisted square antiprismatic structure in this complex and from the relatively high steric strain at the water coordination site as a result of the presence of methyl groups at the alpha-position with respect to the Gd(III)-bound O atoms of THP.

Activation of a PARACEST Agent for MRI through Selective Outersphere Interactions with Phosphate Diesters

“…This assignment was based on the identification of the alcohol proton and bound water resonances in acetonitrile and acetonitrile/water mixtures and comparison of the chemical shift of the alcohol resonances with the CEST spectrum 24,27,43. This assignment is also supported by the very rapid exchange rate constant for the water ligand in Ln( S-THP ) 3+ that makes it unlikely that the water ligand will contribute to the CEST spectrum 44. The large pH dependence of the PARACEST effect of these complexes is attributed, in part, to the ionization of the Ln( S-THP ) 3+ complexes to form a new species 30.…”

Being Excited by Lanthanide Coordination Complexes: Aqua Species, Chirality, Excited-State Chemistry, and Exchange Dynamics

“…That this rate is independent of complex structure in this short series is consistent with a late transition-state structure for the dissociative water interchange process. 108 Further support for this premise is provided by data for (S)-[Gd(THP)] 3+ sas the triflate salt 135 swhich exists in aqueous solution as >95% of the TSAP structure. A rate of 2 × 10 7 s -1 (298 K) was also measured here by 17 O NMR methods, notwithstanding the tripositive charge on the complex.…”

Static and Dynamic Stereochemistry of Chiral Ln DOTA Analogues

“…Naturally, this cannot be achieved on the sp 2 carboxylic carbon, but it becomes possible on a carbinolic derivative, THP (THP = 1,4,7,10tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane), depicted in Figure 7. [37][38][39][40][41] Following a procedure similar to what outlined for DOTMA in Figure 5, we can predict that the (SSSS)configuration of the ligand will lead to D coordination, as shown in Figure 7.…”