Copper(II) complexes of hydrolysis products of the anticancer bis(3,5-dioxopiperazin-1-yl)alkanes. Displacement of co-ordinated carboxylate ligands by deprotonated amide groups in basic solution

Abstract

The copper(II) complexes of the diacid diamide ^–O₂CCH₂(H₂NOCCH₂)NCH₂CHRN(CH₂CONH₂)-CH₂CO₂^–(R = H, L³; Me, L⁴) which have in-plane 2N_amine′ 2 O_carboxylate ligands at pH 6 undergo amide group deprotonation in basic solution to give CuN(amine)₂N^–(amide)₂ chromophores resulting from the displacement of the in-plane carboxylate ligands by the superior σ-donating, deprotonated, amide nitrogens. The concentration pK_a values for the deprotonations at 25 °C, I= 0.1 mol dm^–3 are 9.19 ± 0.02 and 9.87 ± 0.02 for [CuL³], and 8.60 ± 0.02 and 9.81 ± 0.02 for [CuL⁴]. The unexpectedly large differences in the first pK_a values is attributed to a steric interaction between the methyl substituent and an axially co-ordinated CH₂CONH₂ group, in the complex of L⁴ which is relieved as a result of the first ionisation step.