Optimizing New Classes of Luminescent Lanthanide Complexes

Emissive lanthanide(III) complexes possess distinct advantages as luminescent reporters in bioassays owing to their unique photophysical properties. Typical luminescent lanthanide complexes consist of Ln(III) ions chelated by chromophore-containing ligands that absorb light that they then transfer to the metal center. Raymond and coworkers (University of California, Berkeley) have demonstrated that 2-hydroxyisophthalamide (IAM)-based antenna ligands are highly efficient sensitizers of visible-emitting lanthanides while providing water-soluble complexes that are stable at the nanomolar concentrations required for practical use. The present study aims to investigate how synthetic modification of IAM-based antenna ligands impacts Tb(III) emission with the goal of determining what ligand attributes result in maximal Tb(III) luminescence. This was pursued through the synthesis of novel IAM ligands that incorporate systematic changes in both the chromophore and the ligand backbone that links the chromophores together. The photophysical properties of the ligands and their Ln(III) complexes were characterized using a variety of spectroscopic techniques, including absorption, emission, circular dichrosim (CD) and circularly polarized luminescence (CPL) spectroscopies, as well as lifetime measurements. (1) A series of substituted IAM ligands was prepared to probe how altering the electronics of the IAM chromophore impacts Tb(III) emission. In addition to spectroscopic characterization, time-dependent density functional theory (TD-DFT) calculations were performed on model systems, which were able to reproduce ligand singlet and triplet energies. The experimental and theoretical results serve as a predictive tool that can be used to guide antenna ligand synthesis. (2) The internal heavy atom effect (spin-orbit coupling) in Tb(III)-IAM complexes was investigated through the synthesis of an iodo-substituted ligand. It was found that the heavy atom effect caused by the halogens outweighs the heavy atom effect induced by the Ln(III) itself. (3) Chiral Tb(III) complexes were developed that exhibit circularly polarized luminescence (CPL) activity. The use of a rigid tetradentate scaffold was successful in yielding Tb(III) complexes that possess both high emission intensity and strong CPL activity. (4) The influence of the ligand backbone on the emission of Tb(III)-IAM complexes was studied using a series of tetradentate JAM ligands that incorporate a variety of backbones. Differences in emission were attributed to changes in ligand-to-Tb(III) energy transfer and in the intrinsic quantum yield of the Tb(III) ion brought about by differences in the coordination environments provided by each of the ligands. (5) Four new IAM-based antenna ligands were developed that incorporate combinations of these modifications that yielded the brightest Tb(III) complexes. The complexes formed with these ligands indeed show strong Tb(III) luminescence, though not as strong as seen previously for Tb(III) complexes with tetra- and octadentate IAM-based ligands.