New tetraazamacrocyclic ligand with neutral pendent groups 1,4,7,10-tetrakis(2-cyanoethyl)-1,4,7,10-tetraazacyclododecane (L) and its cobalt(II), nickel(II) and copper(II) complexes: synthesis, structural characterization and antitumor activity

A new tetraazamacrocyclic ligand (L) with four neutral 2-cyanoethyl pendent groups, and its divalent transition-metal complexes [Co(L) (NO3)]NO3 . H2O (1), [Ni(L) (NO3)]NO3 . 3H(2)O (2) and [Cu(L) (H2O)] (NO3)(2) (3) have bee n synthesized. The crystal structures of 1 and 3 have been determined by X- ray analysis. In complex 1 the cobalt atom is coordinated by four nitrogen atoms and two oxygen atoms of a nitrate anion, which define a distorted oct ahedron. The other nitrate ion lies in the lattice as a counter ion. Comple x 3 is five-coordinated by four nitrogen atoms and an axial aqua ligand, wh ich form a tetragonal pyramid. In complex 3 the two nitrate anions exist as counter ions. Pharmaceutical tests showed that all three metal complexes e xhibit antitumor activity against HL-60 and BEL-7404 tumor cell lines in vi tro, even at a concentration of 10(-8) mol l(-1). Complex 1 can partially c leave supercoiled pBR 322 DNA to form nicked DNA in aerobic solution, and c omplex 3 can convert double strand DNA into nicked DNA completely in the pr esence of MPA. Complex 3 causes perturbation to K562 tumor cell lines in th e G(1) phase. (C) 2000 Elsevier Science Ltd All rights reserved.