Intramolecular Hydrogen Bonding Restricts Gd–Aqua‐Ligand Dynamics. (11th April 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Angewandte Chemie. Volume 129:Number 20(2017)
• Page Start: 5695
• Page End: 5698
• Publication Date: 2017-04-11
• Subjects: Aqua-Ionen-Dynamik -- Gadolinium-Komplexe -- Moleküldynamik -- Relaxivität; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201702274
• Languages: English
• ISSNs: 0044-8249

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.