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

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 Cu 2+. 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.