title: Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics.
abstract: Aqua ligands can undergo rapid internal rotation about the M-O bond. For magnetic resonance contrast agents, this rotation results in diminished relaxivity. Herein, we show that an intramolecular hydrogen bond to the aqua ligand can reduce this internal rotation and increase relaxivity. Molecular modeling was used to design a series of four Gd complexes capable of forming an intramolecular H-bond to the coordinated water ligand, and these complexes had anomalously high relaxivities compared to similar complexes lacking a H-bond acceptor. Molecular dynamics simulations supported the formation of a stable intramolecular H-bond, while alternative hypotheses that could explain the higher relaxivity were systematically ruled out. Intramolecular H-bonding represents a useful strategy to limit internal water rotational motion and increase relaxivity of Gd complexes.
authors.affiliation: A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Suite 2301, Charlestown, MA, 02129, USA.
authors.forename: Eszter
authors.initials: E
authors.lastname: Boros
authors.affiliation: Department of Biological Engineering and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
authors.forename: Raja
authors.initials: R
authors.lastname: Srinivas
authors.affiliation: A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Suite 2301, Charlestown, MA, 02129, USA.
authors.forename: Hee-Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Biochemistry, The University of Arizona, 1306 E. University Boulevard, Tucson, AZ, 85721-0041, USA.
authors.forename: Arnold M
authors.initials: AM
authors.lastname: Raitsimring
authors.affiliation: Department of Chemistry and Biochemistry, The University of Arizona, 1306 E. University Boulevard, Tucson, AZ, 85721-0041, USA.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Astashkin
authors.affiliation: Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, IL, 60439, USA.
authors.forename: Oleg G
authors.initials: OG
authors.lastname: Poluektov
authors.affiliation: Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, IL, 60439, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Niklas
authors.affiliation: Department of Biological Engineering and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Horning
authors.affiliation: Department of Biological Engineering and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Tidor
authors.affiliation: A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Suite 2301, Charlestown, MA, 02129, USA.
authors.forename: Peter
authors.identifier: 0000-0002-3179-6537
authors.initials: P
authors.lastname: Caravan
mesh_terms: D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D014867:Water / Q000737:chemistry
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D008024:Ligands; D014867:Water; D005682:Gadolinium
keywords: aquo-ion dynamics; gadolinium complexes; molecular dynamics; relaxivity