Rational Design of Lanthanide-Binding Tags to Optimize Magnetic Anisotropy in Paramagnetic Protein NMR

Due to their exceptional anisotropic magnetic properties, lanthanide ion (Ln3+) complexes are of great utility in many fields of chemistry, including magnetic materials, biomedical imaging, and nuclear magnetic resonance (NMR) spectroscopy. How to achieve large magnetic anisotropies in the Ln3+ complexes coordinated with open-chain ligands is still a challenge. In this study, we started from the open-chain 4PS-PyMTA ligand and assessed the magnetic anisotropy using installed Ln3+ coordinating pendants by increasing size and rigidity. This approach yielded Ln3+ complexes with increasing magnetic anisotropies. The magnetic anisotropy and conformational dynamics of these open-chain 4PS-PyMTA-based Ln3+ complexes were evaluated by NMR spectroscopy. The impact of the coordination arms on the magnetic anisotropy was further characterized by the ligand field parameters derived from europium luminescence spectra. These data show that the design strategy yielded an efficient way to enhance the conformational rigidity of the Ln3+ chelating moiety and the ligand field strength, which underpins magnetic anisotropy. The magnitudes of pseudocontact shifts and residual dipolar couplings obtained with these 4PS-PyMTA-derived tags installed on a protein rival those obtained previously with synthetically less accessible cyclen-based Ln3+ tags. Our work provides a practical strategy to open-chain Ln3+ complexes with large magnetic anisotropies and straightforward synthetic protocols.