Europium(III) macrocyclic complexes with alcohol pendant groups as chemical exchange saturation transfer agents.
Paramagnetic lanthanide(III) complexes that contain hyperfine-shifted exchangeable protons offer considerable advantages over diamagnetic molecules as chemical exchange saturation transfer (CEST) agents for MRI. As part of a program to investigate avenues to improve the sensitivity of such agents, the CEST characteristics of europium(III) macrocyclic complexes having appended hydroxyethyl groups were investigated. The CEST spectrum of the asymmetrical complex, EuCNPHC3+, shows five distinct peaks for each magnetically nonequivalent exchangeable proton in the molecule. The CEST spectra of this complex were fitted to NMR Bloch theory to yield exchange rates between each of six exchanging proton pools (five on the agent plus bulk water). Exchange between the Eu3+-bound hydroxyl protons and bulk water protons was slow in dry acetonitrile but accelerated incrementally upon stepwise addition of water. In pure water, exchange was too fast to observe a CEST effect. The utility of this class of europium(III) complex for CEST imaging applications is ultimately limited by the small chemical shifts induced by the hydroxyl-appended ligands of this type and the resulting small Deltaomega values for the exchangeable hydroxyl protons.
Woods
Mark
M
Macrocyclics, 2110 Research Row, Suite 425, Dallas, Texas 75235, USA.
Woessner
Donald E
DE
Zhao
Piyu
P
Pasha
Azhar
A
Yang
Meng-Yin
MY
Huang
Ching-Hui
CH
Vasalitiy
Olga
O
Morrow
Janet R
JR
Sherry
A Dean
AD
D000438:Alcohols / Q000737:chemistry*; D003500:Cyclization; D005063:Europium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy
D000438:Alcohols; D005063:Europium