THE CRYSTAL-STRUCTURE OF [CU(HAPH)]CLO4.1.6H2O AND THE CLEAVAGE OF DNA BY ANALOGS OF THE METAL-BINDING CORE OF BLEOMYCIN

An X-ray diffraction study of [Cu(HAPH)](ClO4)· 1.61H2O was carried out. The structure of [Cu(C17- H20N7)](ClO4)·1.61H2O was determined for a monoclinic crystal in C2/c with cell constants a= 25.6516(21), b=8.0478(7), c=23.624(17) Å, β= 118.114(5)° and Z=8. The structure was refined to R=0.064 for 2897 unique observed reflections. The Cu(HAPH)+ cation is a distorted square pyramid with the CuII center 0.062 Å above the least-squares plane defined by pyridine (N1), amine (N18), deprotonated amide (N9) and imidazole (N13) donors of HAPH; CuII is displaced toward imidazole (N22). The imidazole (N22) adjacent to the secondary amine serves as the axial donor of the square pyramid. CuN distances are as follows: CuN1, 1.952(5); CuN18, 2.124(5); CuN9, 2.013(5); CuN13, 1.998(5); CuN22, 2.167(6) Å. The in-plane imidazole ring experiences a greater perturbation in the bond between the coordinated N and the 'C4' carbon compared to the axial imidazole. A 450 base pair restriction fragment of plasmid pT181 DNA and superhelical plasmid pT181 DNA were treated with FeII(HAPH), FeII(SAPH-3), FeII- (AMPHIS), Fe(edta)2- and FeII(BLM). FeII(BLM) cutting of linear DNA was c. ten-fold greater than FeII(HAPH). The small molecule systems follow the reactivity order FeII(HAPH) (4X)>FeII(AMPHIS); FeII(HAPH) (200X)>FeII(SAPH-3) or Fe(edta)2-. A lack of DNA cleavage fragments derived from cuts at positions 3′ to cytidine bases was noted Cutting of superhelical plasmid DNA into linear plasmid DNA and further fragmentation was shown to be concentration dependent for FeII(HAPH). © 1990.