A Novel Strategy for the Design of 8‐Hydroxyquinolinate‐Based Lanthanide Bioprobes That Emit in the Near Infrared Range

Abstract

A new polydentate tripodal ligand T2soxMe was synthesized to take advantage of the chelating effect of tridentate 8-hydroxyquinolinate subunits. Potentiometric and spectrophotometric titrations reveal seven pK(a) values of between 3.7 and 10.2. In water, the use of T2soxMe leads to thermodynamically stable and soluble Ln(III) complexes at physiological pH, with conditional stability constants in the range log beta(11)=7.8-8.6. The chelates are resistant toward hydrolysis and show interesting photophysical properties, particularly in the near infrared (NIR) range. The emission lifetimes of the Nd(III) and Yb(III) complexes recorded in D(2)O and H(2)O suggest the absence of water molecules in the first coordination sphere of the metal ions. Moreover, the low energy of the triplet state allows efficient energy transfer from the ligand to the metal ions: in water at pH 7.4, the sensitization efficacy of the NIR luminescence reaches 75 and approximately 100 % for Nd(III) and Yb(III), respectively, leading to overall quantum yields of 0.027 and 0.13 %; Er(III) luminescence is also detected. According to the WST-1 test, the Yb(III) podate at concentrations of up to 250 microM does not display sizeable cytotoxicity for Jurkat cells after 24 h of incubation. Finally, the same podate is shown to couple to human serum albumin, leading to an increase of 50 % in the NIR-luminescence intensity.