Studies on DNA binding properties of new Schiff base ligands using spectroscopic, electrochemical and computational methods: Influence of substitutions on DNA-binding

In this work, five new Schiff base ligands were synthesized and characterized by H-1 NMR, C-13 NMR, FT-IR, UV-Vis and elemental analysis (CHN). L-1, L-2 and L-3, were derived from condensation of 2-Hydroxy-5-bromobenzaldehyde with 4-aminobenzoic acid, 3-aminobenzoic acid and 3-amino-4-methylbenzoic acid with 1:1 M ratio, respectively. While, L-4 and L-5 were prepared from condensation of 4-aminobenzoate with 3-ethoxy-2-hydroxybenzaldehyde and 3-methoxy-2-hydroxybenzaldehyd with 1:1 M ratio, respectively. Furthermore, the crystal structure of L-4 and L-5 were determined by single crystal X-ray analysis. The interaction of Schiff base ligands with fish sperm DNA (PS-DNA) was investigated under physiological conditions using fluorescence quenching, UV-Vis spectroscopy, molecular docking and molecular dynamics (MD) simulation methods. The estimated binding constants (k(b)) for the DNA-Ligands complexes were 8.9 x 10(4) M-1, 6.8 x 10(4) M-1, 1.2 x 10(5) M-1, 2.3 x 10(5) M-1, 1.7 x 10(5) M-1 for L-1, L-2, L-3, L-4 and L-5, respectively. Based on similarity of the ligands structures and their K-b values, their affinity for binding to FS-DNA follow as: L-3 > L-1 > L-2 and L-4 > L-5. The results revealed that ligands with stronger electron donating substituents, have higher DNA-binding ability than the others. Also, molecular docking results show that all of the synthesized ligands are minor groove binders and H-bond interactions have dominant role in the stability of ligand-DNA complexes. (C) 2018 Elsevier B.V. All rights reserved.