Journal article
The long and short of it: the influence of N-carboxyethyl versus N-carboxymethyl pendant arms on in vitro and in vivo behavior of copper complexes of cross-bridged tetraamine macrocycles
Dalton transactions : an international journal of inorganic chemistry, Vol.2007(21), pp.2150-2162
04/16/2007
DOI: 10.1039/b702938a
PMCID: PMC4289607
PMID: 17514336
Abstract
A cross-bridged cyclam ligand bearing two N-carboxymethyl pendant arms (1) has been found to form a copper(II) complex that exhibits significantly improved biological behavior in recent research towards (64)Cu-based radiopharmaceuticals. Both the kinetic inertness and resistance to reduction of Cu-1 are believed to be relevant to its enhanced performance. To explore the influence of pendant arm length on these properties, new cross-bridged cyclam and cyclen ligands with longer N-carboxyethyl pendant arms, 2 and 4, and their respective copper(II) complexes have been synthesized. Both mono- as well as di-O-protonated forms of Cu-2 have also been isolated and structurally characterized. The spectral and structural properties of Cu-2 and Cu-4, their kinetic inertness in 5 M HCl, and electrochemical behavior have been obtained and compared to those of their N-carboxymethyl-armed homologs, Cu-1 and Cu-3. Only the cyclam-based Cu-1 and Cu-2 showed unusually high kinetic inertness towards acid decomplexation. While both of these complexes also exhibited quasi-reversible Cu(II)/Cu(I) reductions, Cu-2 is easier to reduce by a substantial margin of +400 mV, bringing it within the realm of physiological reductants. Similarly, of the cyclen-based complexes, Cu-4 is also easier to reduce than Cu-3 though both reductions are irreversible. Biodistribution studies of (64)Cu-labeled 2 and 4 were performed in Sprague Dawley rats. Despite comparable acid inertness to their shorter-armed congeners, both longer-armed ligand complexes have poorer bio-clearance properties. This inferior in vivo behavior may be a consequence of their higher reduction potentials.
Details
- Title: Subtitle
- The long and short of it: the influence of N-carboxyethyl versus N-carboxymethyl pendant arms on in vitro and in vivo behavior of copper complexes of cross-bridged tetraamine macrocycles
- Creators
- Katie J. Heroux - University of New HampshireKatrina S. Woodin - University of New HampshireDavid J. Tranchemontagne - University of New HampshirePeter C. B. Widger - University of New HampshireEvan Southwick - University of New HampshireEdward H. Wong - University of New HampshireGary R. Weisman - University of New HampshireSterling A. Tomellini - University of New HampshireThaddeus J. Wadas - Mallinckrodt (United States)Carolyn J. Anderson - MallinckrodtScott Kassel - University of California, San DiegoJames A. Golen - University of Massachusetts DartmouthArnold L. Rheingold - University of California, San Diego
- Resource Type
- Journal article
- Publication Details
- Dalton transactions : an international journal of inorganic chemistry, Vol.2007(21), pp.2150-2162
- DOI
- 10.1039/b702938a
- PMID
- 17514336
- PMCID
- PMC4289607
- NLM abbreviation
- Dalton Trans
- ISSN
- 1477-9226
- eISSN
- 1477-9234
- Language
- English
- Date published
- 04/16/2007
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984313073002771
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