Binuclear and tetranuclear Zn(ii) complexes with thiosemicarbazones: synthesis, X-ray crystal structures, ATP-sensing, DNA-binding, phosphatase activity and theoretical calculations

Two Zinc(ii) complexes [Zn(4)(L(1))(4)]·2H(2)O (1) and [Zn(2)(L(2))(2)]·2H(2)O (2) of pyruvaldehydethiosemicarbazone ligands are reported. The complexes were characterized by elemental analysis, IR, NMR, UV-vis spectroscopy and by single-crystal X-ray crystallography. X-ray crystal structure determinations of the complexes show that though Zn : ligand stoichiometry is 1 : 1 in both the complexes, the molecular unit is tetranuclear for 1 and binuclear for 2. Both the complexes show selective sensing of ATP at pH 7.4 (0.01 M HEPES) in CH(3)CN–H(2)O (9 : 1) medium in the presence of other anions like AcO(−), NO(3)(−), F(−), Cl(−), H(2)PO(4)(−), HPO(4)(2−) and P(2)O(7)(2−). The UV-titration experiments of complexes 1 and 2 with ATP results in binding constants of 2.0(±0.07) × 10(4) M(−1) and 7.1(±0.05) × 10(3) M(−1) respectively. The calculated detection limits of 6.7 μM and 1.7 μM for 1 and 2 respectively suggest that the complexes are sensitive detectors of ATP. High selectivity of the complexes is confirmed by the addition of ATP in presence of an excess of other anions. DFT studies confirm that the ATP complexes are more favorable than those with the other inorganic phosphate anions, in agreement with the experimental results. Phosphatase like activity of both complexes is investigated spectrophotometrically using 4-nitrophenylphosphate (NPP) as a substrate, indicating the complexes possess significant phosphate ester hydrolytic efficiency. The kinetics for the hydrolysis of the substrate NPP was studied by the initial rate method at 25 °C. Michaelis–Menten derived kinetic parameters indicate that rate of hydrolysis of the P–O bond by complex 1 is much greater than that of complex 2, the k(cat) values being 212(±5) and 38(±2) h(−1) respectively. The DNA binding studies of the complexes were investigated using electronic absorption spectroscopy and fluorescence quenching. The absorption spectral titrations of the complexes with DNA indicate that the CT-DNA binding affinity (K(b)) of complex 1 (2.10(±0.07) × 10(6) M(−1)) is slightly greater than that of 2 (1.11(±0.04) × 10(6) M(−1)). From fluorescence spectra the apparent binding constant (K(app)) values were calculated and they are found to be 5.41(±0.01) × 10(5) M(−1) for 1 and 3.93(±0.02) × 10(5) M(−1) for 2. The molecular dynamics simulation demonstrates that the Zn(ii) complex 1 is a good intercalator of DNA.