1,2-hydroxypyridonate/terephthalamide complexes of gadolinium(III): synthesis, stability, relaxivity, and water exchange properties.
Four new Gd(III) complexes based on the 1,2-hydroxypyridinone chelator have been synthesized and evaluated as potential magentic resonance imaging contrast agents. Previously reported work examining Gd-TREN-1,2-HOPO (3; HOPO = hydroxypyridinone) suggests that the 1,2-HOPO unit binds strongly and selectively to Gd(III), encouraging further study of the stability and relaxivity properties of this class of compounds. Among the new complexes presented in this paper are the homopodal Gd-Ser-TREN-1,2-HOPO (Gd-5) and three heteropodal bis-1,2-HOPO-TAM complexes (Gd-6, Gd-7, and Gd-8; TAM = terephthalamide). Conditional stability constants were determined, and all pGd values are in the range of 18.5-19.7, comparable to other analogous HOPO complexes and currently used commercial contrast agents. Relaxivities for all complexes are about twice those of commercial agents, ranging from 7.8 to 10.5 mM(-1) s(-1) (20 MHz; 25 degrees C), and suggest two innersphere water molecules in fast exchange. Luminescent measurements were used to verify the number of coordinated waters for Gd-5, and VT (17)O NMR experiments were employed for the highly soluble Gd-TREN-bis-1,2-HOPO-TAM-N3 (Gd-8) complex to measure a fast water exchange rate, (298)k(ex) = 1/tau(M), of 5.1 (+/-0.4) x 10(8) s(-1) ((298)tau(M) approximately 2 ns).
Werner
Eric J
EJ
Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Kozhukh
Julia
J
Botta
Mauro
M
Moore
Evan G
EG
Avedano
Stefano
S
Aime
Silvio
S
Raymond
Kenneth N
KN
D002614:Chelating Agents / Q000737:chemistry; D015195:Drug Design; D008024:Ligands; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010795:Phthalic Acids / Q000737:chemistry*; D011522:Protons; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D002614:Chelating Agents; D008024:Ligands; D009942:Organometallic Compounds; D010795:Phthalic Acids; D011522:Protons; C500102:gadolinium(III) 1,2-hydroxypyridonate; D014867:Water