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:
-
[1]
- 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}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 17 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
High-Relaxivity Magnetic Resonance Imaging Contrast Agents Part 2: Optimization of Inner- and Second-Sphere Relaxivity
journal, January 2010
- Jacques, Vincent; Dumas, Stéphane; Sun, Wei-Chuan
- Investigative Radiology, Vol. 45, Issue 10
Hydrogen bonding of carbonyl, ether, and ester oxygen atoms with alkanol hydroxyl groups
journal, April 1997
- Lommerse, Jos P. M.; Price, Sarah L.; Taylor, Robin
- Journal of Computational Chemistry, Vol. 18, Issue 6
How Does Internal Motion Influence the Relaxation of the Water Protons in Ln III DOTA-like Complexes?
journal, January 2002
- Dunand, Frank A.; Borel, Alain; Merbach, André E.
- Journal of the American Chemical Society, Vol. 124, Issue 4
Pushing the Sensitivity Envelope of Lanthanide-Based Magnetic Resonance Imaging (MRI) Contrast Agents for Molecular Imaging Applications
journal, July 2009
- Aime, Silvio; Castelli, Daniela Delli; Crich, Simonetta Geninatti
- Accounts of Chemical Research, Vol. 42, Issue 7
Gd(iii) complex of a monophosphinate-bis(phosphonate) DOTA analogue with a high relaxivity; Lanthanide(iii) complexes for imaging and radiotherapy of calcified tissues
journal, January 2009
- Vitha, Tomáš; Kubíček, Vojtěch; Kotek, Jan
- Dalton Transactions, Issue 17
Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T 1 contrast agents
journal, March 2009
- Caravan, Peter; Farrar, Christian T.; Frullano, Luca
- Contrast Media & Molecular Imaging, Vol. 4, Issue 2
The effects of membrane potential and lanthanides on the conformation of the Ca2+-transport ATPase in sarcoplasmic reticulum
journal, March 1986
- Jona, I.; Martonosi, A.
- Biochemical Journal, Vol. 234, Issue 2
Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications
journal, September 1999
- Caravan, Peter; Ellison, Jeffrey J.; McMurry, Thomas J.
- Chemical Reviews, Vol. 99, Issue 9
Dielectric Relaxation and Solvation Dynamics of Water in Complex Chemical and Biological Systems
journal, June 2000
- Nandi, Nilashis; Bhattacharyya, Kankan; Bagchi, Biman
- Chemical Reviews, Vol. 100, Issue 6
The Gadolinium(III)−Water Hydrogen Distance in MRI Contrast Agents
journal, June 2003
- Caravan, Peter; Astashkin, Andrei V.; Raitsimring, Arnold M.
- Inorganic Chemistry, Vol. 42, Issue 13
pH-Dependent Modulation of Relaxivity and Luminescence in Macrocyclic Gadolinium and Europium Complexes Based on Reversible Intramolecular Sulfonamide Ligation
journal, August 2001
- Lowe, Mark P.; Parker, David; Reany, Ofer
- Journal of the American Chemical Society, Vol. 123, Issue 31
High Relaxivity Magnetic Resonance Imaging Contrast Agents Part 1: Impact of Single Donor Atom Substitution on Relaxivity of Serum Albumin-Bound Gadolinium Complexes
journal, January 2010
- Dumas, Stéphane; Jacques, Vincent; Sun, Wei-Chuan
- Investigative Radiology, Vol. 45, Issue 10
CHARMM: The biomolecular simulation program
journal, July 2009
- Brooks, B. R.; Brooks, C. L.; Mackerell, A. D.
- Journal of Computational Chemistry, Vol. 30, Issue 10
Avogadro: an advanced semantic chemical editor, visualization, and analysis platform
journal, August 2012
- Hanwell, Marcus D.; Curtis, Donald E.; Lonie, David C.
- Journal of Cheminformatics, Vol. 4, Issue 1
A smooth particle mesh Ewald method
journal, November 1995
- Essmann, Ulrich; Perera, Lalith; Berkowitz, Max L.
- The Journal of Chemical Physics, Vol. 103, Issue 19
Pulsed ENDOR Study of Water Coordination to Gd 3+ Complexes in Orientationally Disordered Systems
journal, March 2004
- Astashkin, Andrei V.; Raitsimring, Arnold M.; Caravan, Peter
- The Journal of Physical Chemistry A, Vol. 108, Issue 11
Structural Optimization of Zn(II)-Activated Magnetic Resonance Imaging Probes
journal, June 2013
- Matosziuk, Lauren M.; Leibowitz, Jonathan H.; Heffern, Marie C.
- Inorganic Chemistry, Vol. 52, Issue 21
Characterization of Gd3+ and Tb3+ Binding Sites on Ca2+, Mg2+-Adenosine Triphosphatase of Sarcoplasmic Reticulum1
journal, January 1984
- Itoh, Naoto; Kawakita, Masao
- The Journal of Biochemistry, Vol. 95, Issue 3
A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model
journal, October 1993
- Bayly, Christopher I.; Cieplak, Piotr; Cornell, Wendy
- The Journal of Physical Chemistry, Vol. 97, Issue 40
Gd(DOTAla): A Single Amino Acid Gd-complex as a Modular Tool for High Relaxivity MR Contrast Agent Development
journal, November 2012
- Boros, Eszter; Polasek, Miloslav; Zhang, Zhaoda
- Journal of the American Chemical Society, Vol. 134, Issue 48
First 17 O NMR Observation of Coordinated Water on Both Isomers of [Eu(DOTAM)(H 2 O)] 3+ : A Direct Access to Water Exchange and its Role in the Isomerization 1
journal, February 2000
- Dunand, Frank A.; Aime, Silvio; Merbach, André E.
- Journal of the American Chemical Society, Vol. 122, Issue 7
Probing the Structure–Relaxivity Relationship of Bis-hydrated Gd(DOTAla) Derivatives
journal, February 2015
- Boros, Eszter; Caravan, Peter
- Inorganic Chemistry, Vol. 54, Issue 5
Structure–Relaxivity Relationships of Serum Albumin Targeted MRI Probes Based on a Single Amino Acid Gd Complex
journal, February 2013
- Boros, Eszter; Caravan, Peter
- Journal of Medicinal Chemistry, Vol. 56, Issue 4
Gd 3+ -Based Magnetic Resonance Imaging Contrast Agent Responsive to Zn 2+
journal, October 2015
- Regueiro-Figueroa, Martín; Gündüz, Serhat; Patinec, Véronique
- Inorganic Chemistry, Vol. 54, Issue 21
Mapping hydration dynamics around a protein surface
journal, November 2007
- Zhang, L.; Wang, L.; Kao, Y. -T.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 47
Gadolinium(iii) complexes as MRI contrast agents: ligand design and properties of the complexes
journal, January 2008
- Hermann, Petr; Kotek, Jan; Kubíček, Vojtěch
- Dalton Transactions, Issue 23
Substitution of lanthanide ions for calcium ions in the activation of bovine prothrombin by activated factor X. High affinity metal-binding sites of prothrombin and the derivatives of prothrombin activation.
journal, June 1976
- Furie, B. C.; Mann, K. G.; Furie, B.
- Journal of Biological Chemistry, Vol. 251, Issue 11
Works referencing / citing this record:
Filling Tricompartmental Ligands with GdIII and ZnII Ions: Some Structural and MRI Studies
journal, November 2018
- Corredoira-Vázquez, Julio; Fondo, Matilde; Sanmartín-Matalobos, Jesús
- Crystals, Vol. 8, Issue 11
Gadolinium as an MRI contrast agent
journal, March 2018
- Kim, Hee-Kyung; Lee, Gang Ho; Chang, Yongmin
- Future Medicinal Chemistry, Vol. 10, Issue 6
Investigations into the effects of linker length elongation on the behaviour of calcium-responsive MRI probes
journal, January 2019
- Connah, Liam; Truffault, Vincent; Platas-Iglesias, Carlos
- Dalton Transactions, Vol. 48, Issue 36
Accelerating water exchange in Gd III –DO3A-derivatives by favouring the dissociative mechanism through hydrogen bonding
journal, January 2019
- Leone, Loredana; Esteban-Gómez, David; Platas-Iglesias, Carlos
- Chemical Communications, Vol. 55, Issue 4
Crystal Structures of DOTMA Chelates from Ce 3+ to Yb 3+ : Evidence for a Continuum of Metal Ion Hydration States
journal, July 2019
- Woods, Mark; Payne, Katherine M.; Valente, Edward J.
- Chemistry – A European Journal, Vol. 25, Issue 42