We have developed a modular architecture for preparing high-relaxivity multiplexed probes utilizing click chemistry. Our system incorporates azide bearing Gd(III) chelates and a trialkyne scaffold with a functional group for subsequent modification. In optimizing the relaxivity of this new complex, we undertook a study of the linker length between a chelate and the scaffold to determine its effect on relaxivity. The results show a strong dependence on flexibility between the individual chelates and the scaffold with decreasing linker length leading to significant increases in relaxivity. Nuclear magnetic resonance dispersion (NMRD) spectra were obtained to confirm a 10-fold increase in the rotational correlation time from 0.049 to 0.60 ns at 310 K. We have additionally obtained a crystal structure demonstrating that modification with an azide does not impact the coordination of the lanthanide. The resulting multi nuclear center has a 500% increase in per Gd (or ionic) relaxivity at 1.41 T versus small molecule contrast agents and a 170% increase in relaxivity at 9.4 T.

A Modular System for the Synthesis of Multiplexed Magnetic Resonance Probes / D.J. Mastarone; V.S.R. Harrison; A.L. Eckermann; G. Parigi; C. Luchinat; T.J. Meade. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 133:(2011), pp. 5329-5337. [10.1021/ja1099616]

A Modular System for the Synthesis of Multiplexed Magnetic Resonance Probes

PARIGI, GIACOMO;LUCHINAT, CLAUDIO;
2011

Abstract

We have developed a modular architecture for preparing high-relaxivity multiplexed probes utilizing click chemistry. Our system incorporates azide bearing Gd(III) chelates and a trialkyne scaffold with a functional group for subsequent modification. In optimizing the relaxivity of this new complex, we undertook a study of the linker length between a chelate and the scaffold to determine its effect on relaxivity. The results show a strong dependence on flexibility between the individual chelates and the scaffold with decreasing linker length leading to significant increases in relaxivity. Nuclear magnetic resonance dispersion (NMRD) spectra were obtained to confirm a 10-fold increase in the rotational correlation time from 0.049 to 0.60 ns at 310 K. We have additionally obtained a crystal structure demonstrating that modification with an azide does not impact the coordination of the lanthanide. The resulting multi nuclear center has a 500% increase in per Gd (or ionic) relaxivity at 1.41 T versus small molecule contrast agents and a 170% increase in relaxivity at 9.4 T.
2011
133
5329
5337
D.J. Mastarone; V.S.R. Harrison; A.L. Eckermann; G. Parigi; C. Luchinat; T.J. Meade
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/431285
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