Redox-active magnetic resonance imaging contrast agents: Studies with thiol-bearing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid derivatives

Bhumasamudram Jagadish, Gerald P. Guntle, Dezheng Zhao, Vijay Gokhale, Tarik J. Ozumerzifon, Ali M. Ahad, Eugene A. Mash, Natarajan Raghunand

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10378-10386
Number of pages9
JournalJournal of Medicinal Chemistry
Volume55
Issue number23
DOIs
StatePublished - Dec 13 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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