title: Characterizing the magnetic susceptibility tensor of lanthanide-containing polymethylated-DOTA complexes.
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. Using17O-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.
authors.affiliation: Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Strickland
authors.affiliation: Office of Intramural Research, Center for Information Technology, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Schwieters
authors.affiliation: Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85748, Garching, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Göbl
authors.affiliation: Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, 20850, USA.
authors.forename: Ana C L
authors.initials: AC
authors.lastname: Opina
authors.affiliation: Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Strub
authors.affiliation: Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, 20850, USA.
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Swenson
authors.affiliation: Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, 20850, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Vasalatiy
authors.affiliation: Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA. tjandran@nhlbi.nih.gov.
authors.forename: Nico
authors.initials: N
authors.lastname: Tjandra
mesh_terms: D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008670:Metals / Q000737:chemistry; D008745:Methylation; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013696:Temperature
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D028581:Lanthanoid Series Elements; D008670:Metals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
keywords: DOTA; Lanthanide; Magnetic susceptibility tensor; PCS; Pseudocontact shift