The synthesis and in vitro testing of a zinc-activated MRI contrast agent.
Zinc(II) plays a vital role in normal cellular function as an essential component of numerous enzymes, transcription factors, and synaptic vesicles. While zinc can be linked to a variety of physiological processes, the mechanisms of its cellular actions are less discernible. Here, we have synthesized and tested a Zn(II)-activated magnetic resonance imaging (MRI) contrast agent in which the coordination geometry of the complex rearranges upon binding of Zn(II). In the absence of Zn(II) water is restricted from binding to a chelated Gd(III) ion by coordinating acetate arms resulting in a low relaxivity of 2.33 mM(-1) x s(-1) at 60 MHz. Upon addition of Zn(II) the relaxivity of the Gd(III)-Zn(II) complex increases to 5.07 mM(-1) x s(-1) and is consistent with one water molecule bound to Gd(III). These results were confirmed by nuclear magnetic relaxation dispersion analysis. There was no observed change in relaxivity of the Gd(III) complex when physiologically competing cations Ca(II) and Mg(II) were added. A competitive binding assay gave a dissociation constant of 2.38 x 10(-4) M for the Gd(III)-Zn(II) complex. In vitro magnetic resonance images confirm that Zn(II) concentrations as low as 100 microM can be detected by using this contrast agent.
Major
Jody L
JL
Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
Parigi
Giacomo
G
Luchinat
Claudio
C
Meade
Thomas J
TJ
D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D005029:Ethylenediamines; D005682:Gadolinium; D008279:Magnetic Resonance Imaging / Q000379:methods; D008958:Models, Molecular; D011522:Protons; D014867:Water / Q000737:chemistry; D015032:Zinc
D003287:Contrast Media; D005029:Ethylenediamines; D011522:Protons; D014867:Water; D005682:Gadolinium; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine