Synthesis, structural characterization and potentiometric studies of divalent metal complexes with an octadentate tetraazamacrocyclic ligand and their DNA cleavage ability

Four new metal complexes with an octadentate macrocyclic ligand [L = 1,4,7, 10-tetrakis(2-carbamoylethyl)-1,4,7,10-tetraazacyclododecane] were synthesi zed and characterized by elemental analyses, IR and MS. These complexes hav e the general formula: M(L)(NO3)(2). nH(2)O [M = Co (1), Ni (2), n = 2; M = Cu (3), Zn (4), n = 1]. The structures of complexes 1, 2 and 3 have been d etermined by X-ray diffraction. [Co(L)(NO3)](NO3). 2H(2)O (1) crystallizes in the triclinic space group P (1) over bar. The refinement converges with R = 0.045 and R-w = 0.057 for 3233 reflections with (I > 2.5 sigma(I)). The Co has an octahedral geometry, and was coordinated with four amine nitroge n atoms of macrocyclic ligand and two or one acylate oxygen atoms derived f rom amide pendant groups. Two water molecules crystallize in the lattice ce ll and two kinds of hydrogen bonds exist between the coordinated acylate gr oup and the water molecules: N(6)-H(27)... O(11) 2.158, N(8)-H(40)... O(12) 2.158 Angstrom or exist between the uncoordinated acylate group and the ni trate ion: N(5)-H(21)... O(8) 2.452, N(7)-H(33)... O(5) 2.256 Angstrom. [Ni (L)(NO3)](NO3). 2H(2)O (2) crystallizes in the monoclinic space group C2/c. The refinement converges with R = 0.044 and R-w = 0.059 for 2726 reflectio ns with (I > 3 sigma(I)). The crystal of complex 2 has high symmetry with a C-2v symmetric operation. The central Ni atom is coordinated to four amine nitrogen atoms of macrocyclic skeleton and two acylate oxygen atoms of pen dant amide groups. The polyhedron of the central atom can be described as a pseudo-octahedron. Two water molecules crystallized in the cell lattice. [ Cu(L)](NO3)(2). H2O (3) crystallizes in the monoclinic space group P2(1)/n. The refinement converges with R = 0.037 and R-w = 0.048 for 3174 reflectio ns with (I > 2.5 sigma(I)). Complex 3 has a five-coordinated pyramid. The b ond lengths of Co-O (av.) 2.088(3), Ni-O 2.089(2) Angstrom are almost equal , and are shorter than Cu-O 2.137(3) Angstrom. On the other hand, the bond lengths of Co-N (av.) and Ni-N (av.) are 2.194(3) and 2.153(2) Angstrom, re spectively. Both of them are longer than Cu-N (av.) 2.0465(3) Angstrom. The potentiometric experiments in aqueous solution showed that the stability c onstants of three complexes were in the range of log K-ML = 17.11-15.00. Th e DNA cleavage results showed that the cobalt complex can effectively cleav e supercoiled DNA to form nicked or linear DNA by performing single strand and double strand scissions under aerobic conditions in the presence of hyd rogen peroxide as co-oxidant. Electron paramagnetic resonance results with the aid of DMPO as trapping agent demonstrated that the cleavage mechanism possibly occurred via hydroxy radical attacking. (C) 2000 Elsevier Science Ltd. All rights reserved.