A series of the copper (II) complexes 5a-d of estrogen-macrocyclic polyamine conjugates were synthesized and characterized. The interactions of complexes 5a-d with DNA were studied by fluorescence spectroscopy and gel electrophoresis under physiological conditions. The results indicate that the conjugated estrogens have increased the cleavage efficiency of Cu[cyclen](2+) while the conjugates display poor binding affinities. The functional groups of D-ring of estrogens may play a key role in deciding binding and cleavage extent of the complexes to DNA.