Synthesis, solid-state, solution, and theoretical characterization of an "in-cage" scandium-NOTA complex

Developing chelators that strongly and selectively bind rare-earth elements (Sc, Y, La, and lanthanides) represents a longstanding fundamental challenge in inorganic chemistry. Solving these challenges is becoming more important because of increasing use of rare-earth elements in numerous technologies, ranging from paramagnets to luminescent materials. Within this context, we interrogated the complexation chemistry of the scandium(III) (Sc³⁺) trication with the hexadentate 1,4,7-triazacyclononane-1,4,7-triacetic acid (H₃NOTA) chelator. This H₃NOTA chelator is often regarded as an underperformer for complexing Sc³⁺. A common assumption is that metalation does not fully encapsulate Sc³⁺ within the NOTA^3- macrocycle, leaving Sc³⁺ on the periphery of the chelate and susceptible to demetalation. Herein, we developed a synthetic approach that contradicted those assumptions. We confirmed that our procedure forced Sc³⁺ into the NOTA^3- binding pocket by using single crystal X-ray diffraction to determine the Na[Sc(NOTA)(OOCCH₃)] structure. Density functional theory (DFT) and ⁴⁵Sc nuclear magnetic resonance (NMR) spectroscopy showed Sc³⁺ encapsulation was retained when the crystals were dissolved. Solution-phase and DFT studies revealed that [Sc(NOTA)(OOCCH₃)]^1- could accommodate an additional H₂O capping ligand. Thermodynamic properties associated with the Sc-OOCCH₃ and Sc-H₂O capping ligand interactions demonstrated that these capping ligands occupied critical roles in stabilizing the [Sc(NOTA)] chelation complex.