Experimental and theoretical evaluation on the antioxidant activity of a copper(ii) complex based on lidocaine and ibuprofen amide-phenanthroline agents

Abstract

A new copper(II) complex, [Cu(LC)(Ibu-phen)(H 2 O) 2 ](ClO 4 ) 2 (LC: lidocaine, Ibu-phen: ibuprofen amidephenanthroline), was synthesized and characterized. The antioxidant activities of the free ligands and the copper(II) complex were evaluated by in vitro experiments and theoretical calculations using density functional theory (DFT). Structures of the ligand Ibu-phen and the complex were identified by 1 H and 13 C NMR, FT-IR spectroscopies, mass spectrometry, thermogravimetric analysis and elemental analysis. The antioxidant potentials of LC and Ibu-phen ligands as well as copper(II) complex were also evaluated by DPPHc, ABTSc + , HOc essays and EPR spectroscopy. The experimental results show that the radical scavenging activity (RSA) at various concentrations is decreased in the following order: copper(II) complex > ascorbic acid > LC > Ibu-phen. Structural and electronic properties of the studied compounds were also analyzed by DFT approach at the M05-2X/6-311++g(2df,2p)//M05-2X/LanL2DZ level of theory. ESP maps and NPA charge distributions show that the highly negative charge regions found on the N and O heteroatoms make these sites more favorable to bind with the central copper ion.Frontier orbital distributions of copper(II) complex indicate that HOMOs are mainly localized at Ibu-phen, while its LUMOs are distributed at LC. Based on natural bond orbitals (NBO) analyses, Cu(II) ion plays as electron acceptor in binding with the two ligands and two water molecules. Thermochemical properties including bond dissociation enthalpy (BDE), ionization energy (IE), electron affinity (EA), proton affinity (PA) characterizing three common antioxidant mechanisms i.e. hydrogen transfer (HT), single electron transfer (SET) and proton loss (PL) were finally calculated in the gas phase and water solvent for two ligands and the copper(II) complex at the same level of theory. As a result, the higher EA and lower BDE and PA values obtained for copper(II) complex show that the complex shows higher antioxidant potential than the free ligands. † Electronic supplementary information (ESI) available: 1 H, 13 C NMR spectra of ligand Ibu-phen, mass spectra of ligand Ibu-phen and copper(II) complex. Cartesian coordinates and molecular enthalpies of copper(II) complex structures for different multiplicities from 2 to 8 optimized at M05-2X/LanL2DZ level of theory in the gas phase. See View Article Online a IC 50 (50% concentration of inhibition for radical scavenging activity). Values are mean AE SD of triplicates.3326 | RSC Adv., 2019,9,[3320][3321][3322][3323][3324][3325][3326][3327][3328][3329][3330][3331][3332][3333][3334][3335] This journal is

Synthesis, Staructure and Redox Properties of Cu(II) Chelate Complexes on the Basis of 2‐(Hydroxyphenyl)‐1H‐benzo[d]imidazol‐1‐yl Phenol Ligands

“…The ability of 2‐(hydroxyphenyl)‐1H‐benzo[d]imidazols and their Cu(II) complexes to readily produce highly stable phenoxyl‐type radicals provide for the antioxidant properties of these compounds. Their scavenging activity was tested using the standard procedure involving the reaction of hydrogen atom transfer to the stable free radical 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) [11,23,24] . The reaction can be spectrophotometrically monitored by measuring decrease in absorption of the intense longest wavelength band (l max =517 nm, ethanol) of DPPH (Figure S29–S32).…”

“…Their scavenging activity was tested using the standard procedure involving the reaction of hydrogen atom transfer to the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). [11,23,24] The reaction can be spectrophotometrically monitored by measuring decrease in absorption of the intense longest wavelength band (l max = 517 nm, ethanol) of DPPH (Figure S29-S32). The degree of the reduction of DPPH ("radical inhibition") was calculated according to the formula: [25] Q ¼ 100 � ðA 0 -A c Þ=A 0 where A 0 is the initial absorbance and A c is the value for added sample concentration c. For the reaction of phenol 3 a with DPPH proceeding at 290 K for 1 hour the value Q 290 = 13.7 %, whereas at 348 K (Figure S29) the value Q 348 increases to 37.8 % and the calculated time needed to consume 50 % of the initial DPPH concentration τ (50) 348 = 154.6 min (Figure S30).…”

“…Metal coordination changes the redox potential and additionally affects its antioxidant capacity. [11] Therefore, the goals of the present work consisted in the synthesis, structural characterization of Cu(II) complexes with the 2,6-di-tert-butylphenol-containing ligands and comparative study of redox activity and stability of the corresponding phenoxyl radicals formed in the oxidation. As the appropriate ligands bearing 2,6di-tert-butylphenol pendants we have chosen 2,6-di-tert-butyl-4-(2-(2-hydroxyphenyl)-1H-benzo [d]imidazol-1-yl)phenols 3 known to exhibit pronounced antioxidant and antiplatelet activities.…”

“…The previous studies [9,10] revealed particularly high antioxidant and antiaggregant properties of benzimidazole derivatives containing spatially hindered phenol moieties efficiently inhibiting oxidative stress. Metal coordination changes the redox potential and additionally affects its antioxidant capacity [11] . Therefore, the goals of the present work consisted in the synthesis, structural characterization of Cu(II) complexes with the 2,6‐di‐ tert ‐butylphenol‐containing ligands and comparative study of redox activity and stability of the corresponding phenoxyl radicals formed in the oxidation.…”

Experimental and theoretical investigation of cyclometalated phenylpyridine iridium(iii) complex based on flavonol and ibuprofen ligands as potent antioxidant

“…The result is totally in agreement with our recent ndings for a Cu(II) complex and others. [49][50][51] Furthermore, in the preliminary phase of another study, we also investigated the in vitro antitumor activity of the Ir(III) complex and two of the ligands towards A549, A2780 and A2780cis cells in comparison with cis-platin as reference. From the results, the studied complex shows considerably higher activity than free ligands and cis-platin (Table S7 and Fig.…”