This report describes a preliminary study to investigate the effect of structural variations in a bifunctional ligand being developed for targeted PARACEST applications. Utilizing Eu-DOTA-4AmCE as the functional PARACEST core, a nitro-aromatic functionality was incorporated to provide the point for conjugation. This intermediate possesses a coordinated water proton signal at 57 ppm which upon saturation produces a 22% decrease in bulk water signal intensity using 10 mM agent. Curve fitting analysis of the CEST spectrum to an exchange model based upon modified Bloch equations gave an estimate of 687 ± 100 μs for the bound water lifetime (τm). Although substantially longer than the 382 μs observed for the parent chelate structure, this water exchange rate remains in the necessary window to produce a significant CEST effect. These findings demonstrate the need to recognize the influence of bifunctional linkers on water exchange rates in lanthanide complexes of this type and the potential for using this functionality as a means of fine-tuning PARACEST performance.
- Bifunctional ligand
- Water exchange