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Structure, stability, and biodistribution of cationic M(CO)(3)](+) (M = Re, Tc-99, Tc-99m) complexes with tridentate amine ligands


Hafliger, P; Mundwiler, S; Ortner, K; Spingler, Bernhard; Alberto, R; Andocs, G; Balogh, L; Bodo, K (2005). Structure, stability, and biodistribution of cationic M(CO)(3)](+) (M = Re, Tc-99, Tc-99m) complexes with tridentate amine ligands. Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 35(1):27-34.

Abstract

Bifunctional chelating molecules linking the fac-Tc-99m(CO)(3)](+) core with targeting biomolecules are required for the development of specific diagnostic radiopharmaceuticals. Diethylenetriamine (1) and N-(pyridin-2-ylmethyl)ethane-1,2-diamine (2) both react readily with (99mT)c(H2O)(3)(CO)(3)](+) in 0.9% saline at micromolar concentrations to form the cationic complexes Tc-99m(1)(CO)(3)](+) (5) and Tc-99m(2)(CO)(3)](+) (6) in quantitative yields. The crystal structures of the corresponding Re or Tc-99 complexes were determined and exhibit in particular the small size of 5. Challenging both Tc-99m complexes 5 and 6 with a 10(4) excess of histidine or cysteine showed no decomposition or ligand exchange after 24 hours and both compounds were also stable against reoxidation to (TcO4)-Tc-99m](-). In normal mice, complex 5 revealed a good and fast clearance from the blood, and most organs. Only limited accumulation in the large intestine was visible after 4 hours. Complex 6 was also excreted relatively quickly from the blood but retention was observed in some tissues after 4 h. In order to illustrate the potential of both ligands to be further functionalized, two derivatives containing potentially DNA binding functionalities, N-(2-Amino-ethyl)-N'-pyren-1-ylmethyl-ethane-1,2-diamine (3) and N-(quinolin-2-ylmethyl)ethane-1,2-diamine (4) were synthesized. The respective Re or Tc-99 complexes were fully characterized. Based on these results, it appears that functionalization of biomolecules with acyclic triamine ligands is biologically relevant. Complex 5 in particular could be used to mimic a terminal amino group in, e. g., a peptide due to its small size and positive charge.

Abstract

Bifunctional chelating molecules linking the fac-Tc-99m(CO)(3)](+) core with targeting biomolecules are required for the development of specific diagnostic radiopharmaceuticals. Diethylenetriamine (1) and N-(pyridin-2-ylmethyl)ethane-1,2-diamine (2) both react readily with (99mT)c(H2O)(3)(CO)(3)](+) in 0.9% saline at micromolar concentrations to form the cationic complexes Tc-99m(1)(CO)(3)](+) (5) and Tc-99m(2)(CO)(3)](+) (6) in quantitative yields. The crystal structures of the corresponding Re or Tc-99 complexes were determined and exhibit in particular the small size of 5. Challenging both Tc-99m complexes 5 and 6 with a 10(4) excess of histidine or cysteine showed no decomposition or ligand exchange after 24 hours and both compounds were also stable against reoxidation to (TcO4)-Tc-99m](-). In normal mice, complex 5 revealed a good and fast clearance from the blood, and most organs. Only limited accumulation in the large intestine was visible after 4 hours. Complex 6 was also excreted relatively quickly from the blood but retention was observed in some tissues after 4 h. In order to illustrate the potential of both ligands to be further functionalized, two derivatives containing potentially DNA binding functionalities, N-(2-Amino-ethyl)-N'-pyren-1-ylmethyl-ethane-1,2-diamine (3) and N-(quinolin-2-ylmethyl)ethane-1,2-diamine (4) were synthesized. The respective Re or Tc-99 complexes were fully characterized. Based on these results, it appears that functionalization of biomolecules with acyclic triamine ligands is biologically relevant. Complex 5 in particular could be used to mimic a terminal amino group in, e. g., a peptide due to its small size and positive charge.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2005
Deposited On:23 Oct 2012 14:09
Last Modified:07 Dec 2017 15:39
Publisher:Taylor & Francis
ISSN:1553-3174
Publisher DOI:https://doi.org/10.1081/SIM-200047534
Other Identification Number:ISI:000228531500005

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