Copper(ii) complexes derived from naphthalene-based halogenated Schiff bases: synthesis, structural analysis, DFT computational studies and in vitro biological activities

Abstract

Two halogenated Schiff bases namely, (E)-1-(((2,6-dichlorophenyl)imino)methyl)naphthalen-2-ol (L1) and (E)-1-(((4-bromo-2,6-dichlorophenyl)imino)methyl)naphthalen-2-ol (L2) were synthesized and reacted with copper(II) nitrate trihydrate in ethanol to give Cu(L1)₂ (1) and Cu(L₂)₂ (2). All the ligands and complexes were successfully characterized using FT-IR, UV-Vis, ¹H & ¹³C-NMR as well as mass spectra and the purity was ascertained by elemental analysis. Electron paramagnetic resonance (EPR) was used to confirm the paramagnetic nature of 1 and 2. Furthermore, the single X-ray crystal structures of 1 and 2 were determined, confirming the formation of mononuclear species in which the Cu(II) center was bonded to two bidentate Schiff bases (L1 or L2) adopting a slightly distorted square planar geometry. Density Function Theory studies revealed that, complex 2 with lowest energy band gap (ΔE) of 2.49 eV is the most reactive among the compounds. α-Amylase and α-glucosidase assays were used to evaluate the antidiabetics potential of the compounds. Complexes 1 and 2 displayed very promising antidiabetic activities with IC₅₀ values of 148.126 mM and 107.786 mM for α-amylase assay while it was 171.559 mM for acarbose (reference drug). The antioxidant potential of the compounds was investigated using nitric oxide (NO), ferric reducing ability power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The compounds showed moderate to good antioxidant activities with 1 and 2 having IC₅₀ values of 100.044 mM and 247.463 mM for NO scavenging assay, which relatively surpass Vanillin with IC₅₀ value of 466.626 mM. All the compounds showed poor to moderate results against Escherichia coli, Staphylococcus aureus, Bacillus substilis, and Pseudomonas aeruginosa. However, none of them were active against Klebsiella pneumoniae. Generally, 1 and 2 displayed better antidiabetes, antioxidant, and antibacterial potential than L1 and L2. Predicted physicochemical and pharmacokinetic properties of all the compounds showed minimal violation of Lipinski's Ro5.