Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics [The Day the Water Stood Still: Intramolecular Hydrogen Bonding to Restrict Gd-Aqua Ligand Dynamics]
Abstract
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:
-
- Harvard Medical School, Charlestown, MA (United States)
- Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
- The Univ. of Arizona, Tucson, AZ (United States)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (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:
- 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. https://doi.org/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. https://doi.org/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 = {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.},
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}
}
Web of Science
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