The
design and synthesis
of hydrazone-based switches with a CF3reporting group
for19F pH imaging using relaxation
rate changes were described. A paramagnetic center was introduced
into the hydrazone molecular switch scaffold by substitution of an
ethyl functional group with a paramagnetic complex. The mechanism
of activation relies on a gradual increase inT1andT2magnetic resonance imaging
(MRI) relaxation times as pH decreases due toE/Zisomerization, which results in a change in the distance
between fluorine atoms and the paramagnetic center. Among the three
possible variants of the ligand, the meta isomer was found to offer
the highest potential changes in relaxation rates due to the significant
paramagnetic relaxation enhancement (PRE) effect and a stable position
of the19F signal, allowing for the tracking of a single
narrow19F resonance for imaging purposes. The selection
of the most suitable Gd(III) paramagnetic ion for complexation was
conducted by theoretical calculations based on the Bloch–Redfield–Wangsness
(BRW) theory, taking into account the electron–nucleus dipole–dipole
and Curie interactions only. The results were verified experimentally,
confirming the accuracy of theoretical predictions, good solubility,
and stability of the agents in water and the reversible transition
between E and Z–H+isomers. The results demonstrate
the potential of this approach for pH imaging using relaxation rate
changes instead of chemical shift.