COPPER(II) COMPLEXES OF AMINOLYSIS PRODUCTS OF THE ANTICANCER BIS(3,5-DIOXOPIPERAZIN-L-YL)ALKANES IN AQUEOUS-SOLUTION

The behaviour in aqueous solution of the copper(II) complexes of tetra amides of 1,2-diaminoethane-N,N,N',N'-tetraethanoic acid (I, R=H, R'=H or Me) and 1,2-diaminopropane-N,N,N',N'-tetraethanoic acid (I, R=Me, R'=H or Me) is described. Potentiometric and spectrophotometric titrat ions confirm that on the addition of base ionization of the equatorial ly coordinated amide groups occurs. The concentration pK(a) values for the copper(II) complexes of ligands I at 25-degrees-C, I=0.1 mol dm-3 NaClO4 are 6.33+/-0.02 and 7.88+/-0.02 for R=R'=H; 6.78+/-0.02 and 8. 66+/-0.02 for R=H, R'=Me; 6.33+/-0.02 and 7.83+/-0.02 for R=Me, R'=H; 6.76+/-0.02 and 8.56+/-0.02 for R=R'=Me. The ionization processes are accompanied by hypsochromic shifts of approximately 130 nm in the elec tronic spectra characteristic of two amide group ionizations with a ch ange from O to N- coordination. In contrast to the corresponding coppe r(II) diacid diamide complexes in which the pK(a) values of axially co ordinated amide groups are lowered because of steric interaction betwe en the methyl substituent, R, and the methylene group attached to the axial amide, in the tetraamide complexes where the ionization processe s involve equatorially coordinated amide groups the methyl substituent R has little or no effect on pK(a) values.