Svetlana Jeremić

Antioxidant and free radical scavenging activity of purpurin

Density functional theory (DFT) calculations were performed to estimate the antioxidant activity of purpurin (1,2,4-trihydroxyanthraquinone-9,10-dione), a naturally occurring anthraquinone pigment. All conformations of purpurin and corresponding radicals, anions, and radical cation were analyzed using the M052X/6-311+G(2df,p) level of theory. The most stable rotamer of purpurin involves three internal hydrogen bonds. The most stable rotamers of purpurin radical and anion were obtained by dehydrogenating hydroxyl groups at C1 and C2, in gaseous and aqueous phases. The antioxidant activity of purpurin was elucidated by its bond dissociation enthalpy and ionization potential. Proton dissociation enthalpies were also computed. On the basis of these values, a one-step hydrogen atom transfer mechanism was invoked, rather than sequential proton loss–electron transfer or electron transfer–proton transfer, to explain the antioxidant activity of purpurin in the gas phase and in nonpolar solvents. In aqueous solution, the sequential proton loss–electron transfer mechanism plays a significant role.Graphical abstract

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.

Importance of hydrogen bonding and aromaticity indices in QSAR modeling of the antioxidative capacity of selected (poly)phenolic antioxidants

The quantitative structure-activity relationship (QSAR) models for predicting antioxidative capacity of 21 structurally similar natural and synthetic phenolic antioxidants was considered. The one-, two- and three-descriptor QSAR models were developed. For this purpose the literature data on the vitamin C equivalent antioxidative capacity (VCEAC) values were used as experimental descriptor of antioxidative capacity. Some thermodynamic and aromaticity properties, as well as the natural bond analysis (NBO) based quantities aimed at measuring the strength of intramolecular hydrogen bonds, were used as independent variables. It was examined whether a combination of these variables can yield a mathematical function that is in good correlation with the VCEAC values. It was shown that a combination of a certain thermodynamic descriptor (related to the single proton loss electron transfer mechanism) with the NBO-based quantities results in several two-descriptor models with the correlation coefficient greater than 0.950. Thus, a significant influence of internal hydrogen bonds on the antioxidative capacity of the studied molecules was confirmed. The best correlation with the VCEAC values was achieved within a three-descriptor QSAR model. This model was obtained by including a magnetic aromaticity index. It was found that aromaticity has only secondary effects on the antioxidative capacity.

Electronic structure study of the biradical pleiadene-like molecules

A detailed electronic structure study of singlet and triplet states of a series of biradicaloid pleiadene-like molecules was performed using the DFT and complete active space methods. It was shown that the singlet–triplet gaps obtained with the B3LYP, B2PLYP, and CASSCF methods are not a monotone function of the number of annelated benzene rings. According to the CASSCF results, 9,10-naphthopleiadene is a triplet biradical, whereas all other members of the series are found to be singlet biradicaloids exhibiting very pronounced biradical character. On the other hand, the B2PLYP calculations revealed that 9,10-anthracenopleiadene is a triplet biradical molecule. A detailed analysis of the local aromaticity of singlet and triplet states of the examined molecules was done by means of the multi-centre delocalization indices, harmonic oscillator model of aromaticity index, and nucleus independent chemical shifts. It was shown that the triplet states are more aromatic than the corresponding singlet electronic states. The difference in aromaticity of the singlet and triplet electronic states becomes smaller along the series of benzannelated pleiadenes. The more pronounced aromatic character of the triplet states can compensate the instability coming from the presence of unpaired electrons, which can explain the fact that the mid-size members of the examined series are found to be triplet biradicals.Graphical abstract

QSAR of the free radical scavenging potency of selected hydroxyanthraquinones

It is well known that anthraquinones are molecules with moderate, but not negligible antioxidative activity. Their chemical behaviour is influenced by different parameters such as thermodynamics, orbital and structural properties, and polarity of environment. To find dependence of antioxidant activity of fourteen selected anthraquinones on the physicochemical parameters, we developed one-, two- and three-descriptor mathematical models. In all quantitative structure–activity relationship models (QSAR), experimentally obtained ABTS values were used as dependent variables. One-descriptor model indicated that in methanol the best correlation give enthalpies that describe stable radical formation following single proton loss, and then transfer of electron. Unexpectedly, the best two-descriptor model shows the best dependence of the experimental results on the combination of the orbital and structural parameters. The best two-parameter model was improved by introducing one thermodynamical parameter, such as bond dissociation enthalpy. On that way the best three-descriptor model was obtained. It indicates that the best insight into the antioxidant capacity of a molecule can be obtained by pooling all types of parameters and influences in a mathematical model.

Mechanisms of scavenging reactions of alizarin with hydroperoxyl and methylperoxyl radicals

Alizarin is anthraquinone with moderate antioxidative capacity. In this work mechanisms of antioxidative activity of alizarin with hydroperoxy and methylperoxy radicals are investigated. All calculations are carried out using B3LYP-D2 method and 6-311+G(d, p) basis set. It is affirmed based on several parameters that hydroxyl group at position 2 is predominant for antiradical activity. PCET mechanism is estimated as favorable mechanism for scavenging activity of alizarin with two selected radicals.

Free radical scavenging potency of 3-hydroxyphenylacetic acid: A DFT study

3-Hydroxyphenylacetic acid (3-HPA) is one of the colon microbial metabolites of flavonoids produced in high concentrations (~300 μM). In this work potency of direct inactivating of selected set of free radicals by 3-HPA was computationally investigated. All calculations were carried out using M05-2X functional with 6-311++G(d, p) basis set coupled with the SMD solvation model. Thermodynamics of three free radical scavenging mechanisms were studied considering electronic properties of 3-HPA and scavenged free radicals. On the basis of obtained results it can be safety predicted that 3-HPA is able to at least in situ effectively scavenge free radicals of different nature, thus contributing to protection from diseases mediated by oxidative stress.