pH-Sensitive Modulation of the Second Hydration Sphere in Lanthanide(III) Tetraamide–DOTA Complexes: A Novel Approach to Smart MR Contrast Media
The authors thank the National Institutes of Health (RR-02584 and CA-84697), the Robert A. Welch Foundation (Grant AT-584), and the Texas Advanced Technology Program for financial assistance.
The lanthanide(III) complexes of three tetraamide DOTA bearing pyridyl, phenolic and hydroxypyridyl substituents have been studied by NMR, luminescence and cyclic voltammetry. The relaxivity profiles of the gadolinium complexes of the pyridyl and phenolic ligands were flat and essentially the same between pH 2 and 8. The hydroxypyridyl ligand, however, exhibited two regions of enhanced relaxivity. The small relaxivity enhancement (25 %) at lower pH (pH 2–4) has been attributed to an increase in the prototropic exchange of the coordinated water molecule while the slightly larger enhancement (84 %) at higher pH (pH 6–9) reflects deprotonation of the ligand amide protons. Deprotonation of the amides results in the formation of an intramolecular acid–base pair interaction with the phenolic protons and this, in turn, causes a highly organized second hydration sphere to come into effect, thereby increasing the relaxivity. The water relaxivity of the Gd3+-hydroxypyridyl complex is further enhanced upon binding to serum albumin.
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Woods, M., Zhang, S., Ebron, V. H., & Sherry, A. D. (2003). pH‐sensitive modulation of the second hydration sphere in lanthanide (III) tetraamide–DOTA complexes: a novel approach to smart MR contrast media. Chemistry–A European Journal, 9(19), 4634-4640.