- Redox-active magnetic resonance imaging contrast agents: Studies with thiol-bearing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid derivatives
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The synthesis and structure-activity relationships of a homologous series of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid gadolinium(III) complexes bearing thiol-terminated alkyl side chains from three to nine carbons in length are reported. The observed binding with human serum albumin (HSA) of the compounds having C-3 through C-7 side chain lengths was inhibited by homocysteine in a manner consistent with single-site binding. The observed binding with HSA of the compounds having C-8 and C-9 side chain lengths was only partly inhibited by homocysteine, consistent with multisite binding. The binding affinity of the C-7 compound could be related to the HSA oxidation state. 2D 1H-1H NMR TOCSY provided evidence of covalent binding of the europium analog of the C-6 compound to HSA-Cys34. The longitudinal water-proton MRI relaxivities of the gadolinium complexes at 7 T increased upon binding to HSA. On the basis of these results, the C-6 and C-7 compounds were identified as promising redox-sensitive MRI contrast agents.
- Jagadish, Bhumasamudram,Guntle, Gerald P.,Zhao, Dezheng,Gokhale, Vijay,Ozumerzifon, Tarik J.,Ahad, Ali M.,Mash, Eugene A.,Raghunand, Natarajan
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p. 10378 - 10386
(2013/02/23)
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