Picolinate-appended tacn complexes for bimodal imaging: Radiolabeling, relaxivity, photophysical and electrochemical...

Based on our previous works involving two 1,4,7-triazacyclononane (tacn)-based ligands Hno2py1pa (1-Picolinic acid-4,7-bis(pyridin-2-ylmethyl)-1,4,7-triazacyclononane) and Hno1pa (1-Picolinic acid-1,4,7-triazacyclononane), we report here the synthesis of analogues bearing picolinate-based π-conjugated ILCT (Intra-Ligand Charge Transfer) transition antenna (HL1, HL2), using regiospecific N-functionalization of the tacn skeleton and their related transition metal complexes (e.g. Cu²⁺, Zn²⁺ and Mn²⁺). Coordination properties as well as their photophysical and electrochemical properties were investigated in order to quantify the impact of such antenna on the luminescent or relaxometric properties of the complexes. The spectroscopic properties of the targeted ligands and metal complexes have been studied using UV-Vis absorption and fluorescence spectrocopies. While the zinc complex formed with HL1 possesses a moderate quantum yield of 5%, complexation of Cu²⁺ led to an extinction of the luminescence putatively attributed to a photo-induced electron transfer, as supported by spectroscopic and electrochemical evidences. The [Mn(L2)]⁺ complex is characterized by a fluorescence quantum yield close to 8% in CH₂Cl₂. The potential interest of such systems as bimodal probes has been assessed from radiolabeling experiments conducted on HL1 and ⁶⁴Cu²⁺ as well as confocal microscopy analyses and from relaxometric studies carried out on the cationic [Mn(L2)]⁺ complex. These results showed that HL1 can be used for radiolabeling, with a radiochemical conversion of 40% in 15 min at 100 °C. Finally, the relaxivity values obtained for [Mn(L2)]⁺, r_1p = 4.80 mM^-1·s^-1 and r_2p = 8.72 mM^-1·s^-1, make the Mn(II) complex an ideal candidate as a probe for Magnetic Resonance Imaging.