Jelena Đorović

Experimental and theoretical study of antioxidative properties of some salicylaldehyde and vanillic Schiff bases

The antioxidative capacity and structure–activity relationships of ten Schiff bases were investigated experimentally and theoretically. All compounds contain the aniline moiety, while the aldehyde part is either salicylaldehyde or vanillin. The DPPH assay was used to test the potential antioxidative activity of these compounds, and DFT study was used to investigate their electronic structures and provide insight into their structure–activity relationships. The effect of the position of the hydroxy, as well other groups present, on the antioxidative activity was examined. The possible radical scavenging mechanism was determined in polar (water and methanol), and nonpolar (benzene) solvents. Based on the experimental and computational results, compounds 7 and 8 exhibit the highest radical scavenging properties.

Free Radical Scavenging Potency of Dihydroxybenzoic Acids

In order to evaluate the free radical scavenging potency of dihydroxybenzoic acids (DHBAs) the Density Functional Theory (DFT) was used. The M05-2X/6-311++G(d,p) and B3LYP-D2/6-311++G(d,p) theoretical models were applied. Three possible antioxidant mechanisms were examined: hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanisms. All of these mechanisms have been studied in nonpolar (benzene and pentylethanoate) and polar solvents (water) using an implicit solvation model (SMD). The following thermodynamic quantities related to these mechanisms were calculated: bond dissociation enthalpy (BDE), ionization potential (IP), and proton affinity (PA). The obtained results indicated the HAT mechanism as the most favourable reaction pathway for antioxidative action of DHBAs in benzene. On the other hand, SPLET is indicated as predominant reaction mechanism in polar solvent. The SET-PT mechanism was not favourable reaction path for antioxidative action in any of the solvents under investigation.

Investigation of the antioxidant and radical scavenging activities of some phenolic Schiff bases with different free radicals

The antioxidant properties of some phenolic Schiff bases in the presence of different reactive particles such as •OH, •OOH, (CH2=CH−O−O•), and -•O2 were investigated. The thermodynamic values, ΔHBDE, ΔHIP, and ΔHPA, were used for this purpose. Three possible mechanisms for transfer of hydrogen atom, concerted proton−electron transfer (CPET), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) were considered. These mechanisms were tested in solvents of different polarity. On the basis of the obtained results it was shown that SET-PT antioxidant mechanism can be the dominant mechanism when Schiff bases react with radical cation, while SPLET and CPET are competitive mechanisms for radical scavenging of hydroxy radical in all solvents under investigation. Examined Schiff bases react with the peroxy radicals via SPLET mechanism in polar and nonpolar solvents. The superoxide radical anion reacts with these Schiff bases very slowly.

Chelate N,O-palladium(II) complexes: synthesis, characterization and biological activity

Four trans chelate N,O-palladium(II) complexes were synthetized starting from salicylaldehyde anil Schiff bases, as ligands. Their structures were elucidated using experimental and theoretical tools. The structures of the theoretically possible cis isomers are examined using the DFT method. The biological activity, in vitro cytotoxic and prooxidative effects against human breast carcinoma MDA-MB-231, human colon carcinoma HCT-116, and human fibroblast healthy MRC-5 cell lines of investigated compounds were determined. Schiff bases show a moderate or weak cytotoxic effect. On the other hand, complexes Pd-1 and Pd-6 show a significant cytotoxic effect on all three cell lines, with IC50 values in the range of 0.6 to 17.1 μM on HCT-116 cells, 7.2 to 55.6 μM on MDA-MB-231 cells and 34.5 to 48.1 μM on MRC-5 cells. Also, Pd-1 and Pd-6 induce extreme oxidative stress in the all treated cell lines. At this stage of investigation, Pd-1 and Pd-6 showed no selectivity towards cancer cells, i.e. they were also cytotoxic to MRC-5 cells to a similar extent. Taking into account these facts, it could be further investigated how the most active substances impact on the type of cell death (apoptotic and/or necrotic pathways).

Hydrogen atom transfer versus proton coupled electron transfer mechanism of gallic acid with different peroxy radicals

Reactions of gallic acid (GA) with alkyl peroxy radicals (methylperoxy, ethylperoxy, iso-propylperoxy, and tert-butylperoxy) were simulated using density functional theory. The reaction is taking place in the way that hydrogen of hydroxy group of GA is transferred to the oxygen of each of peroxy radical. A newly formed radical is stabilized with delocalization of spin density over entire molecule, while the harmful peroxy radical is neutralized. These simple reactions can occur by two different, non-exclusive mechanisms: hydrogen atom transfer and proton coupled electron transfer. The competition between these mechanisms depends on both the solvent and the nature the free radicals. The main differences of these mechanisms are described, together with corresponding thermodynamic and kinetic consequences. The potency of this antioxidative action was thermodynamically and kinetically estimated for hydrogen atom transfer (HAT) and proton coupled electron transfer (PCET) mechanisms. The first one was estimated by calculating bond dissociation energy (ΔGBDE), while the second one was examined using the activation barriers necessary for this action (transition state theory (TST)), as well as using the zero-curvature tunneling effect (ZCT). Additionally, the analysis of single occupied molecular orbitals (SOMOs) in transition states was used to examine differences between HAT and PCET mechanisms.

DFT study of free radical scavenging activity of erodiol

Antioxidant activity of erodiol was examined at the M05-2X/6-311+G(d,p) level of theory in the gas and aqueous phases. The structure and energy of radicals and anions of the most stable erodiol rotamer were analyzed. To estimate antioxidant potential of erodiol, different molecular properties were examined: bond dissociation enthalpy, proton affinity together with electron transfer energy, and ionization potential followed by proton dissociation enthalpy. It was found that hydrogen atom transfer is the prevailing mechanism of erodiol behavior in gas; whereas single electron transfer followed by proton transfer and sequential proton loss electron transfer mechanisms represent the thermodynamically preferred reaction paths in water.

Study of the structure, prooxidative, and cytotoxic activity of some chelate copper(II) complexes

The six chelate N,O-copper(II) complexes were synthesised starting from salicylaldehyde anil Schiff bases, as ligands. Their structure is elucidated using experimental and theoretical tools. In vitro biological activities, i.e. cytotoxic and prooxidative effects against human epithelial mammary gland/breast metastatic carcinoma MDA-MB-231, epithelial colorectal carcinoma HCT-116, and foetal lung fibroblast healthy MRC-5 cell lines of investigated compounds are also determined. Complexes Cu-1, Cu-6, and especially Cu-7 showed significant cytotoxic effects, with IC50 values comparable with effects of positive control CisPt. In addition, investigated complexes induced extreme oxidative and nitrosative stress in all treated cell lines. The most prominent effect is observed on HCT-116 cells, and on MRC-5 cells, while MDA-MB-231 cells showed higher resistance to the investigated cell lines, giving us direction towards the substances with more specific selectivity.

Synthesis, spectroscopic characterization (FT-IR, FT-Raman, and NMR), quantum chemical studies and molecular docking of 3-(1-(phenylamino)ethylidene)-chroman-2,4-dione

The experimental and theoretical investigations of structure of the 3-(1-(phenylamino)ethylidene)-chroman-2,4-dione were performed. X-ray structure analysis and spectroscopic methods (FTIR and FT-Raman, 1H and 13C NMR), along with the density functional theory calculations (B3LYP functional with empirical dispersion corrections D3BJ in combination with the 6-311 + G(d,p) basis set), were used in order to characterize the molecular structure and spectroscopic behavior of the investigated coumarin derivative. Molecular docking analysis was carried out to identify the potency of inhibition of the title molecule against humans Ubiquinol-Cytochrome C Reductase Binding Protein (UQCRB) and Methylenetetrahydrofolate reductase (MTHFR). The inhibition activity was obtained for ten conformations of ligand inside the proteins.

Theoretical analysis of the experimental UV-Vis absorption spectra of some phenolic Schiff bases

ABSTRACT The time-dependent density functional theory (TDDFT) was applied in conjunction with the natural bond orbital analysis to examine the UV-Vis properties of 10 phenolic Schiff bases. The calculations were performed with different functionals, but main discussion refers to results obtained at the B3LYP/6-311+G(d,p) level of theory. The approach based on the natural localised molecular orbital clusters indicates similar behaviour for majority of examined compounds. The HOMO (“highest occupied molecular orbital”) cluster is delocalised over the ring which is electron richer, the HOMO-1 cluster is spread over the other ring, whereas the LUMO (“lowest unoccupied molecular orbital”) cluster is situated on the imino group. The two bands at long wavelengths correspond to the HOMO → LUMO and HOMO-1 → LUMO transitions, i.e. from both A and B rings to the imino group. The next band originates from a transition from the imino group to the imino group. The band at the smallest wavelengths originates from a transition from the A ring to the A ring, or from the B ring to the B ring. Our findings are in very good agreement with the existing literature data.

Spectroscopic and theoretical investigation of the potential anti-tumor and anti-microbial agent, 3-(1-((2-hydroxyphenyl)amino)ethylidene)chroman-2,4-dione

The coumarin-orthoaminophenol derivative was prepared under mild conditions. Based on crystallographic structure, IR and Raman, 1H and 13C NMR spectra the most applicable theoretical method was determined to be B3LYP-D3BJ. The stability and reactivity parameters were calculated, in the framework of NBO, QTAIM and Fukui functions, form the optimized structure. This reactivity was then probed in biological systems. The antimicrobial activity towards four bacteria and three fungi species was examined and activity was proven. In vitro cytotoxic effects, against human epithelial colorectal carcinoma HCT-116 and human healthy lung MRC-5 cell lines, of the investigated substance are also tested. Compound showed significant cytotoxic effects on HCT-116 cells, while on MRC-5 cells showed no cytotoxic effects. The effect of hydroxy group in ortho-position on the overall reactivity of molecule was examined through molecular docking with Glutathione-S-transferases.