PH-DEPENDENT COORDINATION MODE OF NEW BLEOMYCIN SYNTHETIC ANALOGS WITH COPPER(II), IRON(II), AND ZINC(II)

The new simplified bleomycin (BLM) mimic ligands L1 and L2 (=a carbamide-attached L1) have been synthesized to study pH-dependent coordination chemistry. Comparison of the protonation constants for L1 (9.8, 7.3, and 5.6 at 25-degrees-C, I = 0.2 (NaClO4)) and L2 (7.8, 6.9, and 3.7) reveals the significance of the carbamide group which is applied to the primary function of the corresponding carbamide of the beta-aminoalanine portion in BLM. The pH-dependent complexation behaviors of L1 and L2 with Cu(II), Fe(II), and Zn(II) were studied with pH-metric titrations. With L1, Cu(II) forms 4-coordinate, square-planar [CuII(H--1L1)H+]2+ (11) at pH < 5, where H--1LH+ is an amide-deprotonated ligand and the terminal NH2 is protonated, and 5-coordinate, square-pyramidal [CuII(H--1L1)]+ (12) at pH > 6, where the terminal NH2 (unprotonated) binds axially with Cu(II). Both of these were isolated and characterized as perchlorate salts. With L1, Zn(II) yields 4-coordinate, tetrahedral [ZnIIL1]2+ (17) at pH < 6 and 5-coordinate [ZnII(H--1L1)]+ (18) at pH > 8. Both 17 and 18 were isolated as perchlorate salts, the first finding in support for the possible 4- and 5-coordinate structures of Zn(II)-BLM at varying pH values. L1, however, does not form a stable complex with Fe(II), while L2 does a possibly stable 16. It is reasoned that the more basic amine donors of L1 prefer protons over Fe(II). Complexation of L2 with Cu(II) occurs at pH > 3, to directly form the 12-like complex [CuII(H--1L2)]+ (15). The X-ray crystal study of [CuII(H--1L2)]+ (15) as a perchlorate salt proves the 5-coordinate, square-pyramidal complex structure. Final R and R. values were 0.056 and 0.084, respectively: C15H20N7O2CuClO4.H2O, triclinic, space group P1 with a = 9.566 (1) angstrom, b = 13.760 (1) angstrom, c = 8.504 (1) (angstrom), and rho(c) = 1.640 g cm-3 for Z = 2 and V = 1035.4 (2) angstrom3.