title: A highly stable gadolinium complex with a fast, associative mechanism of water exchange.
abstract: The stability and water exchange dynamics of gadolinium (GdIII) complexes are critical characteristics that determine their effectiveness as contrast agents for magnetic resonance imaging (MRI). A new heteropodal GdIII chelate, [Gd-TREN-bis(6-Me-HOPO)-(TAM-TRI)(H2O)2] (Gd-2), is presented which is based on a hydroxypyridinate (HOPO)-terephthalamide (TAM) ligand design. Thermodynamic equilibrium constants for the acid-base properties and the GdIII complexation strength of TREN-bis(6-Me-HOPO)-(TAM-TRI) (2) were measured by potentiometric and spectrophotometric titration techniques, respectively. The pGd of 2 is 20.6 (pH 7.4, 25 degrees C, I = 0.1 M), indicating that Gd-2 is of more than sufficient thermodynamic stability for in vivo MRI applications. The water exchange rate of Gd-2 (kex = 5.3(+/-0.6) x 107 s-1) was determined by variable temperature 17O NMR and is in the fast exchange regime - ideal for MRI. Variable pressure 17O NMR was used to determine the volume of activation (DeltaV) of Gd-2. DeltaV for Gd-2 is -5 cm3 mol-1, indicative of an interchange associative (Ia) water exchange mechanism. The results reported herein are important as they provide insight into the factors influencing high stability and fast water exchange in the HOPO series of complexes, potentially future clinical contrast agents.
authors: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors: Marlon K
authors: MK
authors: Thompson
authors: Mauro
authors: M
authors: Botta
authors: Gaëlle
authors: G
authors: Nicolle
authors: Lothar
authors: L
authors: Helm
authors: Silvio
authors: S
authors: Aime
authors: André E
authors: AE
authors: Merbach
authors: Kenneth N
authors: KN
authors: Raymond
mesh_terms: D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D003287:Contrast Media; D008024:Ligands; D009942:Organometallic Compounds; D014867:Water; D005682:Gadolinium