The effect on DNA and the antibacterial activity of a series of high nuclearity nickel compounds with three, four and five metal atoms were examined. The compounds have a mixed ligand composition with salicylhydroxamic acid and di-2-pyridyl-ketonoxime as chelate agents. In the trinuclear compound Ni(3)(shi)(2)(Hpko)(2)(py)(2)(1), two metal ions show a square planar geometry while the third one is in an octahedral environment. The compounds with four and five nickel atoms construct metallacrown cores with two distinct connectivities. The tetranuclear vacant metallacrown [12-MC(Ni(II)N(Hshi)2(pko)2)-4](2+) shows the connectivity pattern [-O-Ni-O-N-Ni-N-](2), while the pentanuclear ([Ni(II)][12-MC(Ni(II)N(shi)2(pko)2)-4])(2+) follows the pattern [-Ni-O-N-](4). Two distinct arrangements of the chelates around the ring metal ions were observed; a 6-5-6-5-6-5-6-5 arrangement for the [12-MC(Ni(II)N(Hshi)2(pko)2)-4] core and a 6-6-5-5-6-6-5-5 arrangement for the [12-MC(Ni(II)N(shi)2(pko)2)-4] core. Magnetic variable temperature susceptibility study of the trinuclear compound revealed the presence of one paramagnetic nickel(II) ion with strong crystal field dependence, with D=5.0(4) cm(-1), g(xy)=2.7(3) and g(z)=2.3(3). The effect of the synthesized Ni(II) complexes on the integrity and electrophoretic mobility of nucleic acids was examined. Only compounds 2, 3 and 4 altered the mobility of pDNA, forming high molecular weight concatamers at low concentrations or precipitates at higher concentrations. Antibacterial activity screening of the above compounds suggests that nickel compounds 2, 3 and 4 were the most active and can act as potent antibacterial agents.