DNA/BSA binding, antidiabetic and antioxidant studies of copper(ii) complexes derived from ONO-tridentate Schiff bases and diimines as auxiliary ligands

Abstract

Six new copper(II) complexes with general molecular formula [CuL1(Phen)] (1), [CuL2(Phen)] (2), [CuL3(Phen)] (3), [CuL1(DM-Phen)] (4), [CuL2(DM-Phen)] (5) and [CuL3(DM-Phen)] (6) (L = (E)-1-(((4-chloro-2-hydroxyphenyl)imino)methyl)naphthalen-2-ol (L1), (E)-1-(((2-hydroxy-5-methylphenyl)imino)methyl)naphthalen-2-ol (L2), (E)-1-(((2-hydroxy-4-nitrophenyl)imino)methyl)naphthalen-2-ol (L3), Phen = 1,10-phenanthroline and DM-Phen = 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized by spectroscopic as well as crystallographic techniques. Molecular structures of 2, 4, 5 and 6 revealed that they are mononuclear species where the copper(II) center is five-coordinated to a pair of oxygen atoms as well as one nitrogen atom from the ligands (L1–L3) and to a pair of nitrogen atoms from the auxiliary ligand (Phen or DM-Phen) conforming to a distorted square pyramid. The binding affinities of ligands L1–L3 and copper(II) complexes 1–6 with calf thymus DNA (ctDNA) and bovine serum albumin (BSA) were evaluated using UV-visible absorption spectroscopy. For ctDNA, all compounds showed hypochromism and bathochromic shifts suggesting intercalative binding, with K_b values ranging from 1.49 × 10⁴ to 2.74 × 10⁵ M⁻¹. The complexes exhibited 3–18-fold higher affinity than ligands, especially those with 2,9-dimethyl-1,10-phenanthroline coligands. BSA titrations of complexes 1–6 revealed hyperchromic shifts at ∼280 nm, with K_b values of 9.59 × 10⁴ to 2.41 × 10⁵ M⁻¹. These moderate-to-strong bindings were enhanced by lipophilic substituents that promote hydrophobic and π-stacking interactions in protein pockets. All of the compounds inhibit α-amylase better than acarbose with complex 5 (IC₅₀ = 0.274 mM) showing the highest activity. For the α-glucosidase assay, only complexes 2 (IC₅₀ = 0.055 mM) and 4 (IC₅₀ = 0.054 mM) outshined acarbose (IC₅₀ = 0.059 mM) while other compounds showed moderate to good α-glucosidase inhibition activity. Antioxidant activities of the free ligands showed better activity than that of the metal complexes with none of the compounds performing better than quercetin in all of the assays explored for this study.