DNA/Protein binding and anticancer activity of Zn(II) complexes based on azo-Schiff base ligands

Abstract

Synthesis of the azo–Schiff base ligands 2-((E)-((4-(diethylamino)phenyl)imino)methyl)-4-((E)-(2-(phenylthio)phenyl)diazenyl)phenol (L1) and-((E)-((4-(diethylamino)phenyl)-imino)methyl)-4-((E)-(2-phenoxyphenyl)diazenyl)phenol (L2) and Zn(II) complexes (C1-C2) containing these ligands have been described. Characterization of the ligands and complexes has been achieved by spectral studies (IR, 1H, 13C, ESI–MS, UV/vis., emission) and structures of C1 and C2 verified by X-ray single crystal analyses. Absorption titration studies on the complexes revealed that these strongly interact with calf thymus DNA (CT-DNA). Calculated equilibrium binding constants (Kb) for C1 and C2 converged to 4.51 × 104 and 3.74 × 104. Protein binding studies of the complexes with BSA have been performed by UV/vis, fluorescence, synchronous and 3D fluorescence spectroscopy. MTT assay toward Hut-78 cell line suggested high cytotoxicity for C1 (IC50: 70 μM) relative to C2 (IC50: 110 µM). Upon irradiation (UV light; λ, 365 nm) the complexes C1 and C2 exhibited cis–trans photo isomerization and after withdrawal of the light these settled back to more stable trans form. Rate constant (k) for photo isomerization of C1 and C2 has been worked out using electronic absorption data (2.29 × 10−2,C1; 2.12 × 10−2 s−1, C2) and supported by theoretical studies (DFT).