Pyridyltriazole-containing Compounds as Zinc-responsive MRI Contrast Agents and Luminescence Probes

Magnetic resonance imaging (MRI) is a versatile imaging modality in modern clinical applications. The use of MRI started to be more powerful since the invention of smart contrast agents, which can selectively respond to a specific stimulus such as a metal ion. This study was focused on GdDO3A-based complexes designed to be zinc-responsive MRI contrast agents by exploiting a new pyridyltriazole moiety as an active arm for a zinc(II) chelator. This active arm was designed to have a coordination displacement ability to give a switch-on MR signal. A series of pyridyltriazole containing compounds were synthesized and examined sequentially. The primary compound containing pyrydyltriazole LnC2 (q = 0) exhibited no response towards zinc(II). Modification by changing the binding orientation of the pyridyltriazole, LnC4 had reduced the steric hindrance allowing one coordination site for water (q = 1); however, it still did not show any change in signal to the presence of zinc(II). Increasing the distance between the active arm and the lanthanide centre via additional carbon linkers (LnC5 and LnC6) gave complexes an open-structure (q = 2). This structure also had low affinity toward zinc(II) and did not provide a switch on response to the MR signal. Addition of a hydroxyl functional group to the pyridyltriazole (LnC7) did not change its coordination mode (q = 2). Incorporation of a carboxylic acid group (LnC8) provided coordination to give a q = 1 complex. Furthermore, it exhibited coordination displacement in response to zinc(II), by modulating its hydration number to give a “switch on” MR signal; the relaxivity increased by 30% from 6.5 to 8.6 mM-1s-1 as a response to one equivalent of zinc(II). Elongation of the linker by replacing it with the tri- and tetra-ethylene glycol (LnC9 and LnC10) changed their relaxivity in response to zinc(II) which was assumed to be a result of a different coordination mode. A series of emissive lanthanide complexes with high fluorescence quantum yields were also synthesized as luminescence probes namely; a click-ready complex (TbC1), water soluble complexes (TbC2a, TbC2b), a polymerizable complex (TbC2c), a dimer complex (TbC2-dimer), tridentate ligand complexes (Tb/Eu(27)3, Tb/Eu(32b)3) and a complex potential for dual-modal fluorescence/MR imaging probe (Tb(GdC8)3).