FLUORINATED RESPONSIVE LANTHANIDE COMPLEXES FOR MAGNETIC RESONANCE

Abstract

A series of novel fluorinated lanthanide complexes has been synthesised for use as responsive probes for 19F MRS and MRI. The careful positioning of the CF3 group within 6.5 Å from the metal ion caused the fluorine longitudinal and transversal relaxation rates to be strongly enhanced. This allows faster MR signal acquisition, reducing the sample concentration and acquisition time required to obtain the desired signal intensity. The lanthanide ion also enhanced the chemical shift sensitivity of the fluorine nucleus to changes in the chemical environment. These characteristics have been exploited to develop responsive probes.
A series of pH reporters containing an aromatic mono-amide arm has been prepared and their pH sensitivity assessed. Deprotonation of the amide proton caused a large variation of the 19F chemical shift. The pKa of the probe was modulated by varying the substituents on the aromatic group and an optimal value of 7.1 was obtained with an ortho cyano substituent. The introduction of phosphinate pendant arms allowed narrower linewidths and faster longitudinal relaxation rates to be achieved.
The spectroscopic properties and the conformational isomerism of the same series of complexes have been analysed. In particular, their 19F NMR chemical shift, relaxation properties and 1H relaxivity characteristics were studied.
A series of complexes bearing different ester functional groups was prepared and their ability as reporters for enzymatic activity assessed. PLE and -chymotripsin recognised the substrate and catalysed its transformation. Modification of the probe structure was revealed by variation of the relative signal intensity of the substrate and product fluorine resonances in the 19F NMR spectrum.
Glycol chitosan conjugates with paramagnetic fluorinated complexes were prepared and their NMR properties assessed. In vivo MRI studies in animal models were undertaken and a selective uptake of the contrast agent in the tumour was observed with the Gd analogue.