Studies on the nuclease activity and interactions of the mixed-polypyridyl [Ni2(1,3-tpbd)(diimine)2(H2O)2]4+ complexes with thioredoxin reductase

Three new nickel(II) complexes formulated as [Ni2(1,3-tpbd)(diimine)2(H2O)2]4+ [1,3-tpbd = N,N,N′,N′-tetrakis(2-pyridylmethyl)benzene-1,3-diamine, where diimine is an N,N-donor heterocyclic base like 1,10-phenanthroline (phen),2,2′-bipyridine (bpy), 4,5-diazafluoren-9-one (dafo)], have been synthesized and structurally characterized by X-ray crystallography: [Ni2(1,3-tpbd)(phen)2(H2O)2]4+ (1), [Ni2(1,3-tpbd)(bpy)2(H2O)2]4+(2) and [Ni2(1,3-tpbd)(dafo)2(H2O)2]4+ (3). Single-crystal diffraction reveals that the metal atoms in the complexes are all in a distorted octahedral geometry and in a trans arrangement around 1,3-tpbd ligand. The interactions of the three complexes with calf thymus DNA (CT-DNA) have been investigated by UV absorption, fluorescence spectroscopy, circular dichroism and viscosity. The apparent binding constant (Kapp) values are calculated to be 1.91 × 105  m−1 for 1, 1.18 × 105  m−1 for 2, and 1.35 × 105  m−1 for 3, following the order 1 > 3 > 2. The higher DNA binding affinity of 1 is due to the involvement in partial insertion of the phen ring between the DNA base pairs. A decrease in relative viscosities of DNA upon binding to 1–3 is consistent with the DNA binding affinities. These complexes efficiently display oxidative cleavage of supercoiled DNA in the presence of H2O2 (250 µ m), with 3 exhibiting the highest nuclease activity. The rate constants for the conversion of supercoiled to nicked DNA are 5.28 × 10−5 s−1 (for 1), 6.67 × 10−5 s−1 (for 2) and 1.39 × 10−4 s−1 (for 3), also indicating that complex 3 shows higher catalytic activity than 1 and 2. Here the nuclease activity is not readily correlated to binding affinity. The inhibitory effect of complexes 1–3 on thioredoxin reductase has also been examined. The IC50 values are calculated to be 26.54 ± 0.57, 31.03 ± 3.33 and 8.69 ± 2.54 µ m, respectively, showing a more marked inhibitory effect on thioredoxin reductase by complex 3 than the other two complexes. Copyright © 2012 John Wiley & Sons, Ltd.