Synthesis of lanthanide tag and experimental studies on paramagnetically induced residual dipolar couplings

Nuclear Magnetic Resonance (NMR) spectroscopy is an indispensable technique for the structure elucidation of molecules and determination of their characteristic interactions. Residual Dipolar Coupling (RDC) is an NMR parameter that provides global orientation information of molecules but necessitates the use of an anisotropic orientation medium for the partial alignment of the target molecule with respect to the magnetic field. Importantly, anisotropic paramagnetic tags have been successful as orienting media in biomolecular NMR applications but their use in small organic molecules remains imperfect due to challenges in designing functional lanthanide complexes with varying degrees of bonding in the Ln(III) inner coordination sphere. In this study, we propose a strategy for the synthesis of the lanthanide tag 4-mercaptomethylpyridine-2,6-dicarboxylic acid, 4-MMDPA and the measurement of RDCs in a target molecule using several paramagnetic lanthanide complexes.

Automated summary

Nuclear Magnetic Resonance (NMR) spectroscopy is essential for determining the structure and interactions of molecules. Residual Dipolar Coupling (RDC) provides global orientation information but requires the use of anisotropic orientation media. Anisotropic paramagnetic tags have been successful in biomolecular NMR, but their use in small organic molecules is still imperfect. This study proposes a strategy for synthesizing a lanthanide tag and measuring RDCs in target molecules.