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Title: Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics [The Day the Water Stood Still: Intramolecular Hydrogen Bonding to Restrict 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. Finally, intramolecular H-bonding represents a useful strategy to limit internal water rotational motion and increase relaxivity of Gd complexes.

Authors:
 [1];  [2];  [1];  [3];  [3];  [4];  [4];  [2];  [2]; ORCiD logo [1]
  1. Harvard Medical School, Charlestown, MA (United States)
  2. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
  3. The Univ. of Arizona, Tucson, AZ (United States)
  4. Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22), Chemical Sciences, Geosciences, and Biosciences Division; National Institutes of Health (NIH), National Institute of Biomedical Imaging and Bioengineering (NIBIB); USDOE
OSTI Identifier:
1374175
Alternate Identifier(s):
OSTI ID: 1379983
Grant/Contract Number:
AC02-06CH11357
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Angewandte Chemie (International Edition)
Additional Journal Information:
Journal Name: Angewandte Chemie (International Edition); Journal Volume: 56; Journal Issue: 20; Journal ID: ISSN 1433-7851
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; ENDOR; Hydrogen bonding; Lanthanides; Molecular Dynamics; Relaxivity

Citation Formats

Boros, Eszter, Srinivas, Raja, Kim, Hee -Kyung, Raitsimring, Arnold M., Astashkin, Andrei V., Poluektov, Oleg G., Niklas, Jens, Horning, Andrew D., Tidor, Bruce, and Caravan, Peter. Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics [The Day the Water Stood Still: Intramolecular Hydrogen Bonding to Restrict Gd-Aqua Ligand Dynamics]. United States: N. p., 2017. Web. doi:10.1002/anie.201702274.
Boros, Eszter, Srinivas, Raja, Kim, Hee -Kyung, Raitsimring, Arnold M., Astashkin, Andrei V., Poluektov, Oleg G., Niklas, Jens, Horning, Andrew D., Tidor, Bruce, & Caravan, Peter. Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics [The Day the Water Stood Still: Intramolecular Hydrogen Bonding to Restrict Gd-Aqua Ligand Dynamics]. United States. doi:10.1002/anie.201702274.
Boros, Eszter, Srinivas, Raja, Kim, Hee -Kyung, Raitsimring, Arnold M., Astashkin, Andrei V., Poluektov, Oleg G., Niklas, Jens, Horning, Andrew D., Tidor, Bruce, and Caravan, Peter. Tue . "Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics [The Day the Water Stood Still: Intramolecular Hydrogen Bonding to Restrict Gd-Aqua Ligand Dynamics]". United States. doi:10.1002/anie.201702274. https://www.osti.gov/servlets/purl/1374175.
@article{osti_1374175,
title = {Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics [The Day the Water Stood Still: Intramolecular Hydrogen Bonding to Restrict Gd-Aqua Ligand Dynamics]},
author = {Boros, Eszter and Srinivas, Raja and Kim, Hee -Kyung and Raitsimring, Arnold M. and Astashkin, Andrei V. and Poluektov, Oleg G. and Niklas, Jens and Horning, Andrew D. and Tidor, Bruce and Caravan, Peter},
abstractNote = {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. Finally, intramolecular H-bonding represents a useful strategy to limit internal water rotational motion and increase relaxivity of Gd complexes.},
doi = {10.1002/anie.201702274},
journal = {Angewandte Chemie (International Edition)},
number = 20,
volume = 56,
place = {United States},
year = {Tue Apr 11 00:00:00 EDT 2017},
month = {Tue Apr 11 00:00:00 EDT 2017}
}

Journal Article:
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