In vitro and in vivo studies of N,N′-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide-copper(II) and rheumatoid arthritis

Sebusi Odisitse, Graham E. Jackson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The thermodynamic equilibria of copper(II), zinc(II) and calcium(II) with N,N′-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide (L1) have been studied at 25 °C and an ionic strength of 0.15 mol dm-3. Spectroscopic studies suggest metal ion complexation promotes deprotonation and coordination of the amide nitrogens resulting in overall tetragonal coordination of Cu2+. Blood-plasma modelling predicts that Cu(II) competes effectively against Zn(II) and Ca(II) for L1 in vivo. Octanol-water partition coefficient studies show that Cu(II)-L1 complexes are reasonably lipophilic. However, the CuL1H-2 species which predominates at the physiological pH of 7.4 has poor superoxide dismutase activity. Bio-distribution experiments showed activity accumulation and retention in the body of about 50% of the injected dose for the [64Cu]Cu(II)-L1 complex after 24 h.

Original languageEnglish
Pages (from-to)453-464
Number of pages12
JournalPolyhedron
Volume27
Issue number1
DOIs
Publication statusPublished - Jan 20 2008

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Octanols
arthritis
Deprotonation
Ionic strength
Complexation
Amides
Pyridine
Superoxide Dismutase
Metal ions
Zinc
Copper
Calcium
pyridines
Blood
Nitrogen
Thermodynamics
Plasmas
blood plasma
copper
Water

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry
  • Materials Chemistry

Cite this

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abstract = "The thermodynamic equilibria of copper(II), zinc(II) and calcium(II) with N,N′-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide (L1) have been studied at 25 °C and an ionic strength of 0.15 mol dm-3. Spectroscopic studies suggest metal ion complexation promotes deprotonation and coordination of the amide nitrogens resulting in overall tetragonal coordination of Cu2+. Blood-plasma modelling predicts that Cu(II) competes effectively against Zn(II) and Ca(II) for L1 in vivo. Octanol-water partition coefficient studies show that Cu(II)-L1 complexes are reasonably lipophilic. However, the CuL1H-2 species which predominates at the physiological pH of 7.4 has poor superoxide dismutase activity. Bio-distribution experiments showed activity accumulation and retention in the body of about 50{\%} of the injected dose for the [64Cu]Cu(II)-L1 complex after 24 h.",
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In vitro and in vivo studies of N,N′-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide-copper(II) and rheumatoid arthritis. / Odisitse, Sebusi; Jackson, Graham E.

In: Polyhedron, Vol. 27, No. 1, 20.01.2008, p. 453-464.

Research output: Contribution to journalArticle

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AB - The thermodynamic equilibria of copper(II), zinc(II) and calcium(II) with N,N′-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide (L1) have been studied at 25 °C and an ionic strength of 0.15 mol dm-3. Spectroscopic studies suggest metal ion complexation promotes deprotonation and coordination of the amide nitrogens resulting in overall tetragonal coordination of Cu2+. Blood-plasma modelling predicts that Cu(II) competes effectively against Zn(II) and Ca(II) for L1 in vivo. Octanol-water partition coefficient studies show that Cu(II)-L1 complexes are reasonably lipophilic. However, the CuL1H-2 species which predominates at the physiological pH of 7.4 has poor superoxide dismutase activity. Bio-distribution experiments showed activity accumulation and retention in the body of about 50% of the injected dose for the [64Cu]Cu(II)-L1 complex after 24 h.

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