Theoretical Evaluation of Oleocanthal Reactive Centers.

BACKGROUND: Decarboxymethyl ligstroside aglycone (Oleocanthal) is an essential component of olive oil. It is therefore interesting to study its metabolism in the human body. In order to find the best possible starting point for this metabolism, a theoretical study was carried out using DFT calculations and docking studies. METHODS: The DFT, B3LYP/6-311++G** and the PCM solvation model calculations were used to study the initial process of Oleocanthal metabolism by the CYP1A2 enzyme. Structures of radicals formed by homolytic dissociation of hydrogen atoms from the Oleocanthal structure were obtained and their properties were studied. Several parameters such as HOMO and LUMO energy gaps, Bond Dissociation Energy (BDE), hardness, and spin density of possible Oleocanthal radicals were taken into account. Docking of Oleocanthal into an enzyme binding pocket was also performed to locate the most probably metabolic site. Detailed analysis of the theoretical results allows the determination of the most likely reaction sites in Oleocanthal. The mode of binding of Oleocanthal to the CYP1A2 enzyme was also predicted. RESULTS: The results of the molecular docking studies are in agreement with the calculated quantum parameters. The theoretical predictions were compared with experimental data available in the scientific literature. A high correlation between theoretical calculations and experimental data was observed. The most likely site of Oleocanthal metabolism was identified. CONCLUSION: The results of our research support the usefulness of theoretical calculations in predicting metabolic pathways.

Substituent Effect versus Aromaticity─A Curious Case of Fulvene Derivatives.

A computational study on amino- and nitro-substituted penta- and heptafulvenes reveals the interplay between the aromaticity and the substituent effect (SE). Ring substitution alone has little influence on the aromaticity, but in combination with an exo substituent of opposite properties, it substantially enhances the cyclic π-electron delocalization. Despite the SE being stronger for ß substitution, only γ substitution leads to higher aromaticity. An explanation is provided by the electron density of delocalized bonds (EDDB) method, which proves to be a valuable tool in analyzing both cyclic delocalization and the SE.

Study of the Structure and Infrared Spectra of LiF, LiCl and LiBr Using Density Functional Theory (DFT).

The paper presents a study of the crystal structure of anhydrous halides LiF, LiCl and LiBr using density functional theory. Models composed of 125 atoms were used for this study. The theoretical values of the lattice parameters and the distribution of charges in the crystals were determined. Using the assumed models at the level of theory DFT/B3LYP/6-31+g*, the theoretical infrared spectra of lithium halides (LiF, LiCl and LiBr) were calculated for the first time. Additionally, measurements of experimental far-infrared (FIR) spectra were performed for these salts. All the obtained theoretical values were compared with experimental data obtained by us and those available in the literature.

Synthesis, Crystal Structures, Lipophilic Properties and Antimicrobial Activity of 5-Pyridylmethylidene-3-rhodanine-carboxyalkyl Acids Derivatives.

The constant increase in the resistance of pathogenic bacteria to the commonly used drugs so far makes it necessary to search for new substances with antibacterial activity. Taking up this challenge, we obtained a series of rhodanine-3-carboxyalkyl acid derivatives containing 2- or 3- or 4-pyridinyl moiety at the C-5 position. These compounds were tested for their antibacterial and antifungal activities. They showed activity against Gram-positive bacteria while they were inactive against Gram-negative bacteria and yeast. In order to explain the relationship between the activity of the compounds and their structure, for selected derivatives crystal structures were determined using the X-ray diffraction method. Modeling of the isosurface of electron density was also performed. For all tested compounds their lipophilicity was determined by the RP-TLC method and by calculation methods. On the basis of the carried-out research, it was found that the derivatives with 1.5 N···S electrostatics interactions between the nitrogen atom in the pyridine moiety and the sulfur atom in the rhodanine system showed the highest biological activity.

A Comparative DFT Study on the Antioxidant Activity of Some Novel 3-Hydroxypyridine-4-One Derivatives.

The current study on the antioxidant activity of kojic acid and 3-hydroxypyridine-4-one derivatives was performed by implementation of density functional theory calculations with the B3LYP hybrid functional and the 6-311++G** basis set in Polarizable Continuum Model of solvation. Compounds under evaluation were previously synthesized by our research group. The DPPH scavenging effect and the IC50 values in mM concentrations were evaluated. Subsequently, various electronic and energetic descriptors such as HOMO and LUMO energy gaps, bonding dissociation enthalpy of an OH bond, ionization potential, electron affinity, hardness, softness, NBOs and spin density of radical and neutral species were used to study antioxidant properties of investigated compounds. The computations detected two compounds, HP3 and HP4, with significant antioxidant activity. Energetic descriptors indicated that the SPLET mechanism is preferred over the other antioxidation mechanism and computational results were in accordance with the experimental results.

Pyrrole and Pyridine in the Water Environment-Effect of Discrete and Continuum Solvation Models.

Properties of pyrrole and pyridine molecules upon different hydrations were investigated through density functional theory. Complexes of studied molecules with a cluster of 50 water molecules were considered, and the polarizable continuum model of solvation (PCM) was also taken into account. For comparative purposes, all mentioned calculations were repeated for single pyrrole and pyridine molecules and their complexes with one water molecule. Aromaticities of solvated pyrrole and pyridine rings were studied using several geometric- and electronic-based aromaticity criteria. Special attention was paid to studying the properties of formed hydrogen bonds between pyrrole or pyridine and either a single water molecule or several water molecules of the cluster. Overall, a comprehensive description of two very important heterocyclic compounds, that is, pyrrole and pyridine, in both discrete and continuum water solutions, is extensively presented.

Synthesis, spectroscopy, and theoretical calculations of some 2-thiohydantoin derivatives as possible new fungicides.

We present the synthesis and structure determination for two thiohydantoin compounds (5-benzylidene-2-sulfanylideneimidazolidin-4-one and 5-cinnamylidene-2-sulfanylideneimidazolidin-4-one), proposed as potential novel fungicides. The exact chemical structure of these molecules has not yet been determined since they can potentially exist in several tautomeric and geometric forms (Z-E isomerism). The geometries of all the theoretically possible structures of the studied compounds were optimised. The calculations were performed at the density functional theory level using the B3LYP functional and the 6-311++G** basis set. Based on our calculations, the most probable structures of the studied compounds were proposed. The theoretical predictions were verified by comparing the calculated IR as well as the 1H and 13C NMR spectra with the experimental data. It was documented that both the studied compounds exist predominantly in the tautomeric structure, in which the movable hydrogen is connected to the nitrogen atom in the hydantoin ring. It has been experimentally proven that one of the studied compounds occurs only as a single structure, whereas the other one exists as a mixture of two geometric isomers. Schematic presentation of synthesis reaction and predicted percentage contents of studied compounds in products mixture.

Antioxidant properties of Aloe vera components: a DFT theoretical evaluation.

Prediction of the antioxidant activity of three Aloe vera components (aloesone, aloe-emodin, and isoeleutheol) was performed based on density functional theory calculations using the B3LYP hybrid functional and the 6-311++ G** basis set. Calculation of highest occupied molecular orbital (HOMO), lowest occupied molecular orbital (LUMO), and Egap revealed that aloe-emodin has the lowest Egap value, indicating good antioxidant activity. Also in terms of electron affinity, softness, electrophilicity, and chemical potential, aloe-emodin is a potent structure with potential high radical scavenging activity. Calculation of the ionisation potential revealed that isoeleutherol likely also possesses a high degree of antiradical scavenging. To study the conjugating system of the radicals, density plots of HOMO, natural bond orbital analyses, and spin density plots were used. According to calculations, the isoeleutherol radical is more delocalised and the most stable radical. Calculated proton affinity values revealed that the most probable antioxidant mechanism is sequential proton loss-electron transfer. Our results were compared with available experimental data. Published experimental data were found to correlate well with our theoretical predictions. These results support the usefulness of theoretical calculations not only for identifying potentially useful structures of studied compounds but also for predicting their relative activity.

Why are rhodanines less efficient reagents in Diels-Alder reactions than isorhodanines? A quantum chemical study.

The reactivity of the 5-arylidenerhodanine and 5-arylideneisorhodanine derivatives in reactions with dimethyl maleate was computationally studied at the DFT(M06-2X)/6-311+G(d,p) theory level. Eight stereoisomers of the reaction products were considered. The effect of the solvent was taken into account by means of the continuous and discrete models for acetic acid (PCM and three CH3COOH molecules). Aromatic stabilization of the transition states was documented by the values of HOMA, NICS(0), and NICS(1) indices. The higher reactivity of the isorhodanine derivative was associated with a relatively low activation energy, ∆Ea (15.2-22.3 kcal mol-1), which is needed to cross the TS. For the rhodanine derivative, higher values of ∆Ea (34.1-36.1 kcal mol-1) were obtained. The reactivity was also studied from the perspective of the frontier molecular orbitals, the energy gaps between the HOMO and LUMO, the flux of electron density, the Fukui functions, f+(r), f-(r), and f0(r), and the global indexes defined in the conceptual DFT, i.e., the electronic chemical potential, chemical hardness, global electrophilicity, and empirical nucleophilicity index.

Raman, surface-enhanced Raman, and density functional theory characterization of (diphenylphosphoryl)(pyridin-2-, -3-, and -4-yl)methanol.

This work presents near-infrared Raman spectroscopy (FT-RS) and surface-enhanced Raman scattering (SERS) studies of three pyridine-α-hydroxymethyl biphenyl phosphine oxide isomers: (diphenylphosphoryl)(pyridin-2-yl)methanol (α-Py), (diphenylphosphoryl)(pyridin-3-yl)methanol (ß-Py), and (diphenylphosphoryl)(pyridin-4-yl)methanol (γ-Py) adsorbed onto colloidal and roughened in oxidation-reduction cycles silver surfaces. The molecular geometries in the equilibrium state and vibrational frequencies were calculated by density functional theory (DFT) at the B3LYP 6-311G(df,p) level of theory. The results imply that the most stable structure of the investigated molecules is a dimer created by two intermolecular hydrogen bonds between the H atom of the α-hydroxyl group (in up (HOU) or down (HOD) stereo bonds position) and the O atom of tertiary phosphine oxide (═O) of the two monomers. Comparison the FT-RS spectra with the respective SERS spectra allowed us to predict the orientation of the hydroxyphosphonate derivatives of pyridine that depends upon both the position of the substituent relative to the ring N atom (in α-, ß-, and γ-position, respectively) and the type of silver substrate.

Chiral recognition in diaziridine clusters and the problem of racemization waves.

Theoretical calculations (B3LYP/6-31+G**) of chiral clusters of diaziridines have been carried out. Five configurations of chiral and nonchiral clusters with up to eight monomers have been considered. The proton transfer within the neutral and protonated clusters has been studied as a possible source of racemization waves. The optical rotatory power (ORP) has been calculated for the neutral and protonated homochiral clusters. The results show that the clusters with alternated chiral molecules are the preferred ones and that the proton transfer proceeds with low energetic barriers in the protonated systems. The ORP results are very dependent on the shape of the clusters and the neutral or protonated state of them.

Theoretical study of dihydrogen bonds between (XH)2, X = Li, Na, BeH, and MgH, and weak hydrogen bond donors (HCN, HNC, and HCCH).

The dihydrogen-bonded (DHB) complexes formed by (XH)2, with X = Li, Na, BeH, and MgH, with one, two, and four protonic molecules (HCN, HNC, and HCCH) have been studied. These complexes have been compared to those of the XH monomers with the same hydrogen bond donor molecules. The energetic results have been rationalized based on the electrostatic potential of the isolated hydridic systems. The electron density properties have been analyzed within the AIM methodology, both at the bond critical points and the integrated values at the atomic basins. Exponential relationships between several properties calculated at the bond critical points (rho,nabla2rho, lambdai, G, and V) and variation of integrated properties (energy, charge, and volume) vs the DHB distance have been obtained.

Effect of dimerization and racemization processes on the electron density and the optical rotatory power of hydrogen peroxide derivatives.

The variation of the electron density properties and optical rotatory power of the monomers and dimers of seven monosubstituted hydrogen peroxide derivatives, HOOX (X = CCH, CH(3), CF(3), t-Bu, CN, F, Cl), upon racemization has been studied using DFT (B3LYP/6-31+G) and MP2 (MP2/6-311+G) methods. The geometrical results have been rationalized on the basis of natural bond orbital (NBO) analysis. The atomic partition of the electron density properties within the atoms in molecules (AIM) methodology has allowed investigating the energy and charge redistribution in the different structures considered. The calculated optical rotatory power (ORP) of the dimers are, in general, twice of the values obtained for the monomers.

Enantioselective chromatography of alkyl derivatives of 5-ethyl-5-phenyl-2-thiobarbituric acid studied by semiempirical AM1 method.

Complexation of alkyl derivatives of 5-ethyl-5-phenyl-2-thiobarbituric acid (2-thiophenobarbital) enantiomers by beta-cyclodextrin was investigated by the AM1 method. The inclusion complexes of beta-cyclodextrin with neutral and anionic forms of these enantiomers have been modeled and energetically optimized. The chiral discrimination of enantiomers was analyzed in terms of differences in the interaction energies. The calculated interaction energies between each enantiomer of the investigated 2-thiobarbiturates and beta-cyclodextrin confirm the ability of beta-cyclodextrin to act as a mobile phase additive in reversed-phase HPLC to separate enantiomers by liquid chromatography and rationalize their order of elution.