Gloria Mazzone

Food Antioxidants: Chemical Insights at the Molecular Level

In this review, we briefly summarize the reliability of the density functional theory (DFT)-based methods to accurately predict the main antioxidant properties and the reaction mechanisms involved in the free radical-scavenging reactions of chemical compounds present in food. The analyzed properties are the bond dissociation energies, in particular those involving OH bonds, electron transfer enthalpies, adiabatic ionization potentials, and proton affinities. The reaction mechanisms are hydrogen-atom transfer, proton-coupled electron transfer, radical adduct formation, single electron transfer, sequential electron proton transfer, proton-loss electron transfer, and proton-loss hydrogen-atom transfer. Furthermore, the chelating ability of these compounds and its role in decreasing or inhibiting the oxidative stress induced by Fe(III) and Cu(II) are considered. Comparisons between theoretical and experimental data confirm that modern theoretical tools are not only able to explain controversial experimental facts but also to predict chemical behavior.

Theoretical Determination of Electronic Spectra and Intersystem Spin-Orbit Coupling: The Case of Isoindole-BODIPY Dyes.

Density functional theory and its time-dependent extension (DFT, TDDFT) has been herein employed to elucidate the structural and electronic properties for a series of isoindole-boron dipyrromethene (isoindole-BODIPY) derivatives. The role played by both the nature and the positions of the substituents on intersystem spin-crossing has been investigated computing the spin-orbit matrix elements between singlet and triplet excited state wave functions weighted by the TDDFT transition coefficients. Their potential therapeutic use as photosensitizers in photodynamic therapy (PDT) is proposed on the basis of their strong absorbance in the red part of the visible spectrum, vertical triplet energies resulting higher than 0.98 eV, and the spin-orbit matrix elements that result to be comparable with different drugs already used in PDT.

Antioxidant properties of several coumarin–chalcone hybrids from theoretical insights

Density functional theory (DFT) and time-dependent formulation of DFT (TDDFT) have been employed to elucidate the structural characteristics, the antioxidant ability, and the UV-Vis absorption properties of a series of coumarin–chalcone derivatives recently synthesized. In addition, to investigate the role of adjacent hydroxyl groups on the antioxidant properties, five additional hybrids were designed and considered in this study. Different antioxidant mechanisms have been investigated. They are hydrogen atom transfer (HAT), electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). Based on the obtained results, the HAT mechanism is proposed as the most important one for the antioxidant protection exerted by this class of compounds. The UV spectra of coumarin–chalcone hybrids are characterized by a band in the region between 300 and 450 nm arising from different electronic transitions. Our investigation confirms the antioxidant properties of these hybrids, and shows that poly-substitution of ring A enhances the antioxidant power of this class of compounds. One of the derivatives, designed in the present work, the 5,6,8-trihydroxy-7-methyl-3-(3′,4′-dihydroxybenzoyl) coumarin, seems to be the most promising candidate as an antioxidant. Accordingly, our calculations strongly encourage the synthesis of coumarin–chalcone hybrids as an important strategy to develop novel compounds with improved antioxidant properties.

Electronic spectra and intersystem spin-orbit coupling in 1,2- and 1,3-squaraines

The main photophysical properties of a series of recently synthetized 1,2‐ and 1,3‐squaraines, including absorption electronic spectra, singlet‐triplet energy gaps, and spin‐orbit matrix elements, have been investigated by means of density functional theory (DFT) and time‐dependent DFT approaches. A benchmark of three exchange‐correlation functionals has been performed in six different solvent environments. The investigated 1,2 squaraines have been found to possess two excited triplet states (T1 and T2) that lie below the energy of the excited singlet one (S1). The radiationless intersystem spin crossing efficiency is thus enhanced in both the studied systems and both the transitions could contribute to the excited singlet oxygen production. Moreover, they have a singlet‐triplet energy gap higher than that required to generate the cytotoxic singlet oxygen species. According to our data, these compounds could be used in photodynamic therapy applications that do not require high tissue penetration.

Density Functional Predictions of Antioxidant Activity and UV Spectral Features of Nasutin A, Isonasutin, Ellagic Acid, and One of Its Possible Derivatives

The antioxidant ability of ellagic acid and some of its derivatives was explored at density functional level of theory within the framework of the following three different reaction mechanisms: hydrogen atom transfer (HAT), electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). Computations were performed in gas phase and in both water and methanol media. Results show that the HAT mechanism is preferred by this class of compounds in all environments, although, in principle, polar solvents should promote the SET-PT and SPLET mechanisms. Among the considered compounds, the derivative not yet experimentally characterized seems to be the most promising candidate as antioxidant. For a more detailed spectroscopic characterization and to help in the identification of these compounds, the simulated UV spectra of all investigated molecules were done by using the time-dependent formulation of density functional theory (TDDFT).

Adsorption of Ethylene, Vinyl, Acetic Acid, and Acetate Species on PdAu(111) and PdAu(100) Surface Alloys: A Cluster Model Study.

The adsorption properties on PdAu surface alloys of ethylene and acetic acid molecules along with their derived vinyl and acetate surface species have been investigated by density functional theory calculations. Large clusters have been used to model second-neighbor Pd monomer pair ensembles on PdAu(100) and PdAu(111) surface alloys. Ethylene and acetic acid are weakly bonded to the Pd monomers, while vinyl and acetate are strongly bonded to both Pd and Au atoms being very stable surface species. The ligand effect of the gold atoms surrounding the Pd monomers has been shown to be stronger in the more dense PdAu(111) surface alloy. Cluster model results are in good agreement with experimental evidence providing important insight on the adsorption bonding modes, the assignment of the infrared features, and the preferred adsorption sites.

Mechanistic aspects of the reaction of Th+ and Th2+ with water in the gas phase.

Density functional theory calculations were performed to study the gas-phase reaction of Th(+) and Th(2+) with water. An in-depth analysis of the reaction pathways leading to different reaction products is presented. The obtained results are compared to experimental data and to the previously studied reactions of U cations with water.

Dimethylplatinum(II) complexes: computational insights into Pt-C bond protonolysis.

A detailed density functional theory (DFT) study of the protonation and subsequent methane elimination reactions of dimethylplatinum(II) complexes in presence of triflic acid in various solvents has been undertaken to contribute to the debate concerning the mechanism of the electrophilic cleavage of the Pt-C bond in Pt(II) complexes. Both mechanisms of direct one-step proton attack at the Pt-C bond (S(E)2) and stepwise oxidative-addition on the central metal followed by reductive elimination (S(E)(ox)) have been explored for a series of dimethylplatinum(II) complexes changing the nature of the ancillary ligands and the solvent. Theoretical calculations show that the most likely mechanism cannot be predicted on the basis of spectator ligands donating properties only. A one-step protonolysis pathway is characteristic for complexes containing P based ligands, whereas for complexes containing N based and, in general, hard poor-donor ligands a common behavior cannot be indicated. Solvent nucleophilicity can influence the rate of the S(E)(ox) rate mechanism, whereas its steric hindrance can induce a change of the preferred mechanism. The hypothesis that five-coordinate methyl hydrido platinum(IV) intermediates might be formed along the S(E)(ox) pathway is not supported. Only six-coordinate Pt(IV) hydride complexes are calculated to be stable intermediates generated by direct protonation at the platinum center. Formation and experimental detection of six-coordinate Pt(IV) hydrides, nevertheless, cannot be considered a definite evidence that a S(E)(ox) mechanism is operative because such intermediates can be also generated by a hydrogen migration to Pt from the carbon atom of the σ-complex methane molecule formed by a S(E)2 attack. For all the examined complexes methane loss occurs by an associative mechanism. Both solvent and anion of the acid can assist methane displacement. Calculations have been also carried out to probe whether the preference for a concerted or a stepwise mechanism should be predicted on the basis of two proposed criteria: metal-complex charge distribution as a consequence of the Pt-C bond polarization and the nature of the highest occupied molecular orbital (HOMO).

Understanding zinc(II) chelation with quercetin and luteolin: a combined NMR and theoretical study.

The Zn(II) chelation with natural flavonoids, quercetin and luteolin, was investigated by the use of NMR spectroscopy and various levels of ab initio calculations. Very sharp phenolic OH (1)H resonances in DMSO-d6 were observed for both free and complexed quercetin which allowed (i) the unequivocal assignment with the combined use of (1)H-(13)C HSQC and HMBC experiments and (ii) the determination of complexation sites which were found to be the CO-4 carbonyl oxygen and the deprotonated C-5 OH group of quercetin and CO-4 carbonyl oxygen and the deprotonated C-5 OH group of luteolin. DOSY experiments allowed the determination of the effective molecular weight of the Zn-quercetin complex which was shown to be mainly 1:1. DFT calculations of the 1:1 complex in the gas phase demonstrated that the C-3 O(-) and CO-4 sites are favored for quercetin at both GGA and LDA approximations and the C-5 O(-) and CO-4 groups of luteolin at the LDA approximation. Quantum chemical calculations were also performed by means of the conductor polarizable model in DMSO by employing various functionals. The energetically favored Zn chelation sites of the 1:1 complex were found to be either the C-3 O(-) and CO-4 or C-5 O(-) and CO-4 sites, depending on the functional used, for quercetin and the C-5 O(-) and CO-4 sites for luteolin.

Coumarin-Chalcone Hybrids as Peroxyl Radical Scavengers: Kinetics and Mechanisms.

The primary antioxidant activity of coumarin-chalcone hybrids has been investigated using the density functional and the conventional transition state theories. Their peroxyl radical scavenging ability was studied in solvents of different polarity and taking into account different reaction mechanisms. It was found that the activity of the hybrids increases with the polarity of the environment and the number of phenolic sites. In addition, their peroxyl radical scavenging activity is larger than those of the corresponding nonhybrid coumarin and chalcone molecules. This finding is in line with previous experimental evidence. All the investigated molecules were found to react faster than Trolox with (•)OOH, regardless of the polarity of the environment. The role of deprotonation on the overall activity of the studied compounds was assessed. The rate constants and branching ratios for the reactions of all the studied compounds with (•)OOH are reported for the first time.