Lanthanide Interactions with Ligands and Biomolecules: Spectroscopic and Extraction Studies

Lanthanides (Ln), also known as rare earth metals, have been utilized for industrial and biological purposes and are commonly encountered in the 3+ oxidation state as Ln³⁺. The presence of Ln in spent nuclear fuel introduces problems during the transmutation and partitioning of actinides (An) due to the Ln high neutron cross-sections. Therefore, designing ligands for Ln³⁺ complexation, can be helpful for their separation from An³⁺ in nuclear technology. Also, the biomimetic roles of Ln³⁺ could be suitable for studying the biological macromolecules, such as the Ca²⁺-binding EF-hand proteins that are otherwise inaccessible for detailed structural analysis. In this study, we report a bis(quinoline)-dipicolinamide ligand (DQPDH2), as well as ortho- nitrobenzyl cage ligands (DM-nitrophen and H2-cage) that bind and/or separate Ln³⁺. We studied DREAM, a Ca²⁺ EF-hand protein, to analyze its interaction with Ln³⁺. UV- Vis absorption and fluorescence spectroscopy, circular dichroism, extraction, isothermal titration calorimetry (ITC) and photophysical spectroscopy were used for studying the interaction of Ln³⁺ and ligands/proteins. Our results indicate that DQPDH2 showed high binding affinity to Ln³⁺ with 1-1 complexation ratio, as confirmed by spectroscopic and solvent extraction studies. The X-ray crystal structure of the Nd³⁺-DQPDH2 complex indicated a 1-1 binding pattern, which is consistent with our spectroscopic studies. DM-nitrophen, showed high binding affinity to Ln³⁺ by absorption spectroscopy and ITC. Photoacoustic calorimetry has been performed on DM-nitrophen and Tb³⁺DM-nitrophen photodissociation and the resulting kinetic and thermodynamic data indicated successful release of Tb³⁺ upon photocleavage of DM-nitrophen. H2-cage showed modest binding affinity with Ln³⁺ by UV-Vis absorption spectroscopy, yet it was also shown to be an effective Ln³⁺ extractant. Fluorescence spectroscopy studies of Ca²⁺ binding proteins with Ln³⁺ showed efficient energy transfer from the protein to central Ln³⁺ and possible conformational changes upon Ln³⁺ binding to protein by observing a decrease in tryptophan emission and an increase in emission of hydrophobic probe and DREAM complex.

In summary, our results demonstrated that dipicolinamide-derived ligands can be used for complexation and separation of Ln³⁺. Furthermore, o-nitrobenzyl cages and Ln³⁺DREAM interaction studies can be used as probes for studying the function of Ca²⁺-binding EF-hand proteins in future.