The effect of structural configuration on the DNA binding and in vitro antioxidant properties of new copper(ii) N2O2 Schiff base complexes

Abstract

The interaction of transition metal complexes with DNA and plasma protein gives insight into the development of new materials for medical and biotechnology applications. Thus, we synthesized new series of copper(II) N,O-Schiff base complexes, [Cu(L¹)₂] (1), [Cu(L²)₂] (2) and [Cu(L³)₂] (3) (HL¹ = 2-(((2-chlorophenyl)imino)methyl)phenol, HL² = 2-(((2-isopropylphenyl)imino)methyl)phenol, and HL³ = 2-(((2-methoxyphenyl)imino)methyl)phenol). The complexes were elucidated by X-ray crystallography, mass spectrometry, cyclic voltammetry, elemental analysis, FT-IR, and UV-visible spectroscopies. The crystal structures of complexes 1 & 2 reveal that the copper(II) centre adopts a slightly distorted square planar geometry bearing two bidentate Schiff base ligands L¹, L², respectively. The ligands adopted a κ²N:O coordination mode via the imine nitrogen and phenolate oxygen atoms. The geometry around the copper(II) centre in complex 3 deviates significantly from an ideal square planar geometry with bond angles O(1)¹–Cu(1)–O(1) and N(1)¹–Cu(1)–N(1) at 88.69(12)° and 99.27(11)°, respectively. The N, N, O, O coordinating atoms from the two ligands adopt a trans-configuration in 1 & 2 and cis-configuration in 3. The interaction of these complexes with calf thymus–DNA by UV/Vis spectroscopies indicated high intrinsic binding constants (K_b) in the range of 10⁴ to 10⁶ M⁻¹. From the binding constant values (K_b), we noted that complex 3 with cis-configuration had the highest K_b value. The in vitro antioxidant properties of the complexes were evaluated using four different assays at different concentrations to evaluate their antioxidant potential. Complex 1, with the lowest IC₅₀ value of 93.28 μM has the highest NO˙ scavenging ability than other complexes and ascorbic acid (reference drug) with IC₅₀ values of 133.41 μM. This study revealed that complex 3 containing the methoxy substituent and cis-configuration had the highest CT-DNA binding affinity and radical scavenging ability. Ab initio simulations of the electronic and structural properties of the complexes were carried out to estimate some quantum chemical properties of these complexes.