Synthesis, Characterization, Photoluminescence, Molecular Docking and Bioactivity of Zinc (II) Compounds Based on Different Substituents

Abstract

Six new zinc(II) complexes were prepared by the reaction of ZnBr₂ or ZnI₂ with 4'-(substituted-phenyl)-2,2':6',2''-terpyridine compounds, bearing p-methylsulfonyl (L¹), p-methoxy (L²) and p-methyl (L³), which were characterized by elemental analysis, FT-IR, NMR and single crystal X-ray diffraction. The antiproliferative properties against Eca-109, A549 and Bel-7402 cell lines and the cytotoxicity test on RAW-264.7 of these compounds were monitored using a CCK-8 assay, and the studies indicate that the complexes show higher antiproliferative activities than cisplatin. The interactions of these complexes with CT-DNA and proteins (BSA) were studied by UV-Vis, circular dichroism (CD) and fluorescent spectroscopy, respectively. The results indicate that the interaction of these zinc(II) complexes with CT-DNA is achieved through intercalative binding, and their strong binding affinity to BSA is fulfilled through a static quenching mechanism. The simulation of the complexes with the CT-DNA fragment and BSA was studied by using molecular docking software. It further validates that the complexes interact with DNA through intercalative binding mode and that they have a strong interaction with BSA.

Keywords: CT-DNA binding; antiproliferative activity; fluorescence quenching; molecular docking; zinc (II) complexes.

Scheme 1

The compounds used in the experiment.

Figure 1

Thermal ellipsoid plot, drawn at the 50% probability level, of [ZnBr₂L¹] (1) with atomic numbering scheme. Selected bond lengths (Å) and angles (°): Zn(1)-N(2) 2.099(2), Zn(1)-N(1) 2.187(2), Zn(1)-N(3) 2.215(2), Zn(1)-Br(2) 2.4065(4), Zn(1)-Br(1) 2.4143(4), N(2)-Zn(1)-N(1) 74.22(8) N(2)-Zn(1)-N(3) 74.27(8), N(1)-Zn(1)-N(3) 146.24(8), N(2)-Zn(1)-Br(2) 138.77(6), N(1)-Zn(1)-Br(2) 98.90(6) N(3)-Zn(1)-Br(2) 96.78(5), N(2)-Zn(1)-Br(1) 108.69(6), N(1)-Zn(1)-Br(1) 97.22(6) N(3)-Zn(1)-Br(1) 104.06(6), Br(2)-Zn(1)-Br(1) 112.512(17).

Figure 2

Solid state emission spectra (excitation at 300 nm) of complexes 1–6 at room temperature.

Figure 3

The UV-vis spectra of complexes (a) 1 and (b) 3 in PBS buffer solution over a period of 72 h.

Figure 4

The curves of antitumor activities of compounds 1–6 against (a) Eca-109, (b) A549 and (c) Bel-7402 cell line.

Figure 5

(a) Microscopic photographs of Eca-109 cancer cells treated with different concentrations of compound 1 and control photographs (C for blank control group, C1 for 2.5 μM cisplatin, C2 for 20 μM cisplatin). (b) The cell viability of compounds 1–6 against RAW264.7.

Figure 6

(a) Fluorescence emission spectra of 1.6 μM BSA in a Tris-HCl buffer (pH = 7.2) solution with series concentration of compounds 4 and 6, and (b) curves for the Stern–Volmer equation as the insets.

Figure 7

Absorption spectra of 20 μM of compounds 1–6 in Tris-HCl buffer.

Figure 8

Docking conformation of complex 1 to (a) BSA and (b) amino acid residues surrounding 1.

Figure 9

Absorption spectra of 20 μM of compounds (a) 1 and (b) 3 in a Tris-HCl buffer (pH = 7.2) solution with series concentrations of CT-DNA. The plots of A₀/(A − A₀) versus the concentration of CT-DNA are shown as the insets.

Figure 9

Absorption spectra of 20 μM of compounds (a) 1 and (b) 3 in a Tris-HCl buffer (pH = 7.2) solution with series concentrations of CT-DNA. The plots of A₀/(A − A₀) versus the concentration of CT-DNA are shown as the insets.

Figure 10

CD spectra of compounds (a) 1 and (b) 3 to CT-DNA at different concentration ratios.

Figure 11

Docking conformation of complex 1 to DNA.