Bioactivity of copper(II) complexes derived from halogenated NO-bidentate Schiff bases: In vitro DNA/BSA, antidiabetics, antioxidant, and computational studies

Three halogenated-substituted bidentate Schiff bases were reacted with copper(II) acetate monohydrate to afford copper(II) complexes with general molecular formula [Cu( L1 ) 2 ] ( 1 ), [Cu( L2 ) 2 ] ( 2 ), and [Cu( L3 ) 2 ] ( 3 ) where L1 = (E)-2-(((3-chloro-4-fluorophenyl)imino)methyl)-5-methoxyphenol, L2 = (E)-2-(((2,6-dichlorophenyl)imino)methyl)-5-methoxyphenol and L3 = (E)-2-((4-bromo-2,6-dichlorophenyl)imino)methyl)-5-methoxyphenol. The compounds were characterized by elemental analysis, spectroscopic techniques and single-crystal X-ray crystallographic analysis was used to confirm the structures of L1 , 2 and 3 . Complexes 2 and 3 adopted slightly distorted square-planar geometries. DFT calculations indicated a stability order of 2 > 3 > 1 based on their binding and Gibbs free energy. The ctDNA binding studies using the UV–Vis spectrometry revealed hypochromism accompanied by slight bathochromic shifts, with binding constants ( K b ) of 8.00 × 10 3 to 3.76 × 10 5 M −1 suggesting predominantly intercalative binding. L1 and L3 showed stronger DNA affinity than their corresponding complexes, attributed to greater planarity and π-stacking. Competitive fluorescence displacement studies also suggest intercalation for L1 , L2 , 1 and 2 (K sv = 9.44–55.7 × 10 4 M −1 ), whereas L3 and 3 showed negligible ethidium bromide displacement, consistent with minor-groove or electrostatic interactions. BSA titrations showed hyperchromic shifts at ~278 nm with red shifts for all the compounds, yielding K b values of 9.59 × 10 4 to 2.04 × 10 5 M −1 , and complexes generally exhibited stronger binding than the ligands. Fluorescence quenching of BSA occurred through a static mechanism (K q = 3.34–14.1 × 10 12 M −1 S −1 ), with K b reaching 1.16 × 10 4 M −1 and one binding site per BSA molecule; L2 showed the highest fluorescence binding affinity. Complex 2 displayed the strongest α-glucosidase inhibition (IC 50 = 0.02 mM) outperforming acarbose (IC 50 = 0.09 mM) while all compounds inhibited α-amylase but less effective than acarbose. The compounds showed poor to fair antioxidant activities with none of the compounds' activity exceeding quercetin. The docking studies corroborate well with the in vitro studies except for the α-glucosidase assay.