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

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.

Copper complexes of N,N′-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide have been evaluated as potential anti-inflammatory agents using potentiometry, biophysical measurements and animal studies.Figure optionsDownload as PowerPoint slide