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Intramolecular Hydrogen Bonding Restricts Gd–Aqua‐Ligand Dynamics
Author(s) -
Boros Eszter,
Srinivas Raja,
Kim HeeKyung,
Raitsimring Arnold M.,
Astashkin Andrei V.,
Poluektov Oleg G.,
Niklas Jens,
Horning Andrew D.,
Tidor Bruce,
Caravan Peter
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201702274
Subject(s) - intramolecular force , hydrogen bond , ligand (biochemistry) , chemistry , crystallography , computational chemistry , molecule , stereochemistry , organic chemistry , receptor , biochemistry
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.