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Characterizing the magnetic susceptibility tensor of lanthanide-containing polymethylated-DOTA complexes

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Abstract

Lanthanide complexes based on the DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) cage are commonly used as phase contrast agents in magnetic resonance imaging, but can also be utilized in structural NMR applications due to their ability to induce either paramagnetic relaxation enhancement or a pseudocontact shift (PCS) depending on the choice of the lanthanide. The size and sign of the PCS for any given atom is determined by its coordinates relative to the metal center, and the characteristics of the lanthanide’s magnetic susceptibility tensor. Using a polymethylated DOTA tag (Ln-M8-SPy) conjugated to ubiquitin, we calculated the position of the metal center and characterized the susceptibility tensor for a number of lanthanides (dysprosium, thulium, and ytterbium) under a range of pH and temperature conditions. We found that there was a difference in temperature sensitivity for each of the complexes studied, which depended on the size of the lanthanide ion as well as the isomeric state of the cage. Using 17O-NMR, we confirmed that the temperature sensitivity of the compounds was enhanced by the presence of an apically bound water molecule. Since amide-containing lanthanide complexes are known to be pH sensitive and can be used as probes of physiological pH, we also investigated the effect of pH on the Ln-M8-SPy susceptibility tensor, but we found that the changes in this pH range (5.0–7.4) were not significant.

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Acknowledgments

The project was funded by the Intramural Research Programs of the National Heart, Lung, and Blood Institute and the Center for Information Technology of the NIH. We also thank Dr. Duck-Yeon Lee of the Biochemical Core Facility, National Heart, Lung, and Blood Institute for expertise and advice regarding mass spectrometry-related experiments. We appreciate the assistance of Dr. James Ferretti in acquiring the 17O NMR spectra.

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Authors and Affiliations

  1. Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Madeleine Strickland, Marie-Paule Strub & Nico Tjandra

  2. Office of Intramural Research, Center for Information Technology, National Institutes of Health, Bethesda, MD, 20892, USA

    Charles D. Schwieters

  3. Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748, Garching, Germany

    Christoph Göbl

  4. Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, 20850, USA

    Ana C. L. Opina, Rolf E. Swenson & Olga Vasalatiy

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  1. Madeleine Strickland
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  2. Charles D. Schwieters
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  3. Christoph Göbl
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  4. Ana C. L. Opina
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  7. Olga Vasalatiy
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  8. Nico Tjandra
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Correspondence to Nico Tjandra.

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Strickland, M., Schwieters, C.D., Göbl, C. et al. Characterizing the magnetic susceptibility tensor of lanthanide-containing polymethylated-DOTA complexes. J Biomol NMR 66, 125–139 (2016). https://doi.org/10.1007/s10858-016-0061-x

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