Search Results (57)

Reactive oxygen species play a significant role in various pathological conditions, driving the need for novel, potent antioxidants. While polyphenols are known for their antioxidant properties, their limited stability and bioavailability present challenges for therapeutic applications. To address these limitations, a series of novel thiazolyl-polyphenolic compounds was synthesized via a multi-step synthetic route incorporating Hantzsch heterocyclization in the final step. The synthesized compounds 7a–k were structurally characterized using spectroscopic techniques, including NMR, MS, and IR. In silico thermodynamic calculations, including HOMO–LUMO gap and bond dissociation enthalpy (BDE) calculations, revealed a promising antioxidant profile for these compounds and indicated that the substitution in position 2 of the thiazole ring does not substantially influence the antioxidant activity conferred by the catechol moiety in position 4. The antioxidant capacity of the synthesized compounds was experimentally validated using a panel of six distinct assays: two radical scavenging assays (ABTS and DPPH) and four electron transfer-based assays (RP, TAC, FRAP, and CUPRAC). The in vitro evaluation demonstrated that compounds 7j and 7k exhibited significantly enhanced antioxidant activity compared to the established antioxidant standards, ascorbic acid and Trolox. These findings suggest that the strategic modifications in position 2 of the thiazole scaffold represent a promising direction for future research aimed at developing novel therapeutic agents with enhanced antioxidant properties. The present study is limited to the in vitro evaluation of compounds based on the N-methyl substituted thiazole scaffold, but future studies can include modifications such as changing the substituent on the thiazole nitrogen, the hydrazone linker or possible insertion of substituents in position 5 of thiazole ring of substituents with various electronic or physico-chemical properties. Full article

Background: Luteolin, a flavonoid with well-documented antioxidant properties, has garnered significant attention for its potential therapeutic effects. Objectives: This study aims to investigate the antioxidant properties of luteolin under the influence of solvents, utilizing computational techniques to elucidate its interactions and its potential role as a modulator of enzymatic activities, particularly with Cytochrome 17A1. Methods: Density Functional Theory (DFT) calculations were employed to determine luteolin’s electronic and structural characteristics. Key aspects analyzed included electron density distribution and the energies of the frontier molecular orbitals (HOMO and LUMO). Free radical scavenging mechanisms were explored by comparing the dissociation enthalpy of the O–H bond in the absence and presence of water molecules. Additionally, molecular docking simulations were performed to assess the interactions of luteolin with Cytochrome 17A1, identifying preferred binding sites and interaction energies. Results: The findings indicate that luteolin possesses distinct structural and electronic features that contribute to its effectiveness in protecting against oxidative stress. However, hydrogen bonding interactions with water molecules were found to influence the dissociation enthalpy of the O–H bond. Docking simulations revealed significant interaction profiles between luteolin and Cytochrome 17A1, suggesting its potential role as a modulator of this protein. Conclusions: This study underscores the therapeutic potential of luteolin and highlights the importance of computational techniques in predicting and understanding the molecular interactions of bioactive compounds with biological targets. The results provide valuable insights that may aid in developing new therapeutic strategies for diseases associated with oxidative stress. Full article

In this work, α-tocopherol and trolox were studied as compounds that have high biological activity. α-Tocopherol is considered a food additive because the refining process of vegetable oils causes the depletion of this vitamin, and thus, its inclusion is required to keep them from oxidizing. Computational tools have determined the antioxidant activity of these additives. The geometries of the studied molecules were optimized using two density functional methods, including M05-2X and M06-2X, in combination with the 6-311++G(2d,2p) basis set. The results indicated that when comparing the antioxidant activity of α-tocopherol and trolox, they were very similar to each other, but α-tocopherol had an antioxidant activity slightly higher, around 1.2 kJ/mol, than trolox. Thus, these additives can be used as polymer additives to protect materials from free-radical-induced stress. To test their applicability in polymeric formulations, flexible polyurethane foams were prepared with varying α-tocopherol ratios and NCO indices (1.0 and 1.1). Increasing the α-tocopherol content reduced the compressive force and altered the mechanical properties, likely due to its presence in the foam structure. This additive not only fine-tuned the mechanical properties but also provided antioxidant effects, enabling multiple enhancements in polymeric products with a single additive. Full article

For square-planar late transition metal pyridine, diimine (Rh, Ir) complexes with hydro-xido, methoxido, and thiolato ligands. We could previously establish sizable metal-O- and S π-bonding interactions. Herein, we report the hydrogenation studies of iridium hydroxido and methoxido complexes, which quantitatively lead to the trihydride compound and water/methanol. The iridium trihydride displays a highly fluctional structure with scrambling hydrogen atoms, which can be described as a dihydrogen hydride system based on NMR and DFT investigations. This contrasts the iridium sulfur compounds, which are not reacting with dihydrogen. According to DFT and LNO-CCSD(T) calculations, hydrogenation of the methoxido complex proceeds by a two-step mechanism, i.e., an oxidative addition step of H₂ to an Ir(III) dihydride intermediate with consecutive reductive O-H elimination of methanol. Based on PNO-CCSD(T) calculations, the reactivity difference between the O- and S-donors can be traced to the stronger H-O bonds in the water/methanol products compared to the S-H bonds in the sulphur congeners, which serves as a driving force for hydrogenation. Full article

The free radical trapping capacities of multiple pyranoanthocyanins in wine storage and ageing were theoretically explored by density functional theory (DFT) methods. Intramolecular hydrogen bonds were detected in all pyranoanthocyanins, and the planarity of the compounds worsened with an increasing dielectric constant in the environment. Solvents significantly influenced the reaction enthalpies; thus, the preferred thermodynamic mechanisms of the free radical scavenging reactions were modified in different phases. This study incorporates hydrogen atom transfer (HAT), proton loss (PL), electron transfer (ET) reactions, and demethylation (De) of methoxy group mechanisms. The three pyranoanthocyanins have the capacity to capture n₁+1 free radicals, where n₁ represents the number of methoxy groups. In the gas phase, they prefer employing the n₁-De-HAT mechanism on the guaiacyl moiety of the B ring, resulting in the formation of a stable quinone or a quinone radical to scavenge free radicals. In the benzene phase, pyranoanthocyanins trap free radicals via a PL−n₁−De−HAT mechanism. In the water phase, the targeted pyranoanthocyanins may dissociate in the form of carboxylate and tend to utilize the n₂−PL−n₁−De−ET mechanism, where n₂ and n₁ represent the number of phenolic groups and methoxy groups, respectively, facilitating multiple H⁺/e⁻ reactions. Full article

Natural flavonoids are renowned for their exceptional antioxidant properties, but their limited water solubility hampers their bioavailability. One approach to enhancing their water solubility and antioxidant activity involves the use of cyclodextrin (CD) inclusion. This study investigated the impact of CD inclusion on the three primary radical scavenging mechanisms associated with flavonoid antioxidant activity, utilizing apigenin as a representative flavonoid and employing density functional theory (DFT) calculations. Initially, the optimized geometries of CD−apigenin inclusion complexes were analyzed, revealing the formation of hydrogen bonds between CD and apigenin. In less polar environments, the inclusion complex strengthened the bond dissociation enthalpies of hydroxyl groups, thereby reducing antioxidant activity. Conversely, in polar environments, the inclusion complex had the opposite effect by lowering proton affinity. These findings align with experimental results demonstrating that CD inclusion complexation enhances flavonoid antioxidant activity in aqueous ethanol solutions. Full article

In this study, we considered the structural stability, electronic properties, and phonon dispersion of the cubic (c-ZrO₂), tetragonal (t-ZrO₂), and monoclinic (m-ZrO₂) phases of ZrO₂. We found that the monoclinic phase of zirconium dioxide is the most stable among the three phases in terms of total energy, lowest enthalpy, highest entropy, and other thermodynamic properties. The smallest negative modes were found for m-ZrO₂. Our analysis of the electronic properties showed that during the m–t phase transformation of ZrO₂, the Fermi level first shifts by 0.125 eV toward higher energies, and then decreases by 0.08 eV in the t–c cross-section. The band gaps for c-ZrO₂, t-ZrO₂, and m-ZrO₂ are 5.140 eV, 5.898 eV, and 5.288 eV, respectively. Calculations based on the analysis of the influence of doping 3.23, 6.67, 10.35, and 16.15 mol. %Y₂O₃ onto the m-ZrO₂ structure showed that the enthalpy of m-YSZ decreases linearly, which accompanies the further stabilization of monoclinic ZrO₂ and an increase in its defectiveness. A doping-induced and concentration-dependent phase transition in ZrO₂ under the influence of Y₂O₃ was discovered, due to which the position of the Fermi level changes and the energy gap decreases. It has been established that the main contribution to the formation of the conduction band is made by the p-states of electrons, not only for pure systems, but also those doped with Y₂O₃. The t-ZrO₂ (101) and t-YSZ (101) surface models were selected as optimal surfaces for water adsorption based on a comparison of their surface energies. An analysis of the mechanism of water adsorption on the surface of t-ZrO₂ (101) and t-YSZ (101) showed that H₂O on unstabilized t-ZrO₂ (101) is adsorbed dissociatively with an energy of −1.22 eV, as well as by the method of molecular chemisorption with an energy of −0.69 eV and the formation of a hydrogen bond with a bond length of 1.01 Å. In the case of t-YSZ (101), water is molecularly adsorbed onto the surface with an energy of −1.84 eV. Dissociative adsorption of water occurs at an energy of −1.23 eV, near the yttrium atom. The results show that ab initio approaches are able to describe the mechanism of doping-induced phase transitions in (ZrO₂+Y₂O₃)-like systems, based on which it can be assumed that DFT calculations can also flawlessly evaluate other physical and chemical properties of YSZ, which have not yet been studied quantum chemical research. The obtained results complement the database of research works carried out in the field of the application of biocompatible zirconium dioxide crystals and ceramics in green energy generation, and can be used in designing humidity-to-electricity converters and in creating solid oxide fuel cells based on ZrO₂. Full article

Leonurus sibiricus L. has great ethnobotanical and ethnomedicinal significance. This study aimed to assess the antioxidant and anti-inflammatory properties of Leonurus sibiricus L. transgenic roots extracts transformed by Rhizobium rhizogenes, with and without the AtPAP1 transcriptional factor. The study determined the total phenolic and flavonoid contents, as well as in vitro antioxidant assays, including hydrogen peroxide and nitric oxide scavenging activity. In addition, in silico computational studies and molecular docking were conducted to evaluate the antioxidant and anti-inflammatory potential of the identified compounds. The ligands were docked to NADPH oxidase, cyclooxygenase 2,5-lipoxygenase, inducible nitric synthase and xanthine oxidase: enzymes involved in the inflammatory process. The total phenolic and flavonoid contents ranged from 85.3 ± 0.35 to 57.4 ± 0.15 mg/g GAE/g and 25.6 ± 0.42 to 18.2 ± 0.44 mg/g QUE/g in hairy root extracts with and without AtPAP1, respectively. H₂O₂ scavenging activity (IC₅₀) was found to be 29.3 µg/mL (with AtPAP1) and 37.5 µg/mL (without AtPAP1 transcriptional factor), and NO scavenging activity (IC₅₀) was 48.0 µg/mL (with AtPAP1) and 68.8 µg/mL (without AtPAP1 transcriptional factor). Leonurus sibiricus L. transformed root extracts, both with and without AtPAP1, are a source of phytochemicals belonging to different classes of molecules, such as flavonoids (catechin and rutin), phenolic compounds (caffeic acid, coumaric acid, chlorogenic acid, ferulic acid) and phenylpropanoid (verbascoside). Among the radicals formed after H removal from the different -OH positions, the lowest bond dissociation enthalpy was observed for rutin (4′-OH). Rutin was found to bind with cyclooxygenase 2, inducible nitric synthases and xanthine oxidase, whereas chlorogenic acid demonstrated optimal binding with 5-lipoxygenase. Therefore, it appears that the Leonurus sibiricus L. transformed root extract, both with and without the AtPAP1 transcriptional factor, may serve as a potential source of active components with antioxidant and anti-inflammatory potential; however, the extract containing AtPAP1 demonstrates superior activities. These properties could be beneficial for human health. Full article

Calorimetric (from both isothermal micro-calorimetry and DSC), chiro-optical, viscometric and rheological data on aqueous solutions of pectic acid and low-methoxyl pectin (LMP), published over decades from different laboratories, have been comparatively revisited. The aim was to arrive at a consistent and detailed description of the behavior of galacturonan as a function of pH, i.e., of the degree of charging (as degree of dissociation, α) of the polyanion. The previously hypothesized pH-induced transition from a 3₁ to a 2₁ helix was definitely confirmed, but it has been shown, for the first time, that the transition is always coupled with loosening/tightening effects brought about by an increase in charge. The latter property has a twofold effect: the former effect is a purely physical one (polyelectrolytic), which is always a loosening one. However, in the very low range of pH and before the beginning of the transition, an increase in charge tightens the 3₁ helix by strengthening an intramolecular—but inter-residue—hydrogen bond. The value of the enthalpy change of 3₁ → 2₁ transition—+0.59 kcal·mol⁻¹—is bracketed by those provided by theoretical modeling, namely +0.3 and +0.8 kcal·mol⁻¹; the corresponding entropy value is also positive: +1.84 cal·mole r.u.⁻¹·K⁻¹. The enthalpic and the entropic changes in chain loosening amount only to about 23% of the corresponding 3₁ → 2₁ changes, respectively. Much like poly(galacturonic acid), the 3₁ conformation of LMP also stiffens on passing from pH = 2.5 to 3.0, to then start loosening and transforming into the 2₁ one on passing to pH = 4.0. Lowering the pH of a salt-free aqueous solution of LMP down to 1.6 brings about a substantial chain–chain association, which is at the root of the interchain junctions stabilizing the acid pH gels, in full agreement with the rheological results. A comparison of the enthalpic data reveals that, at 85 °C, LMP in acidic pH conditions has lost its initial order by about 2.3 times more than pectic acid brought from low charging to full neutralization (at α = 1.0) at 25 °C. A proper combination of experiments (enthalpic measurements) and theory (counterion condensation polyelectrolyte theory) succeeded in demonstrating, for the first time ever, a lyotropic/Hofmeister effect of the anion perchlorate in stabilizing the more disordered form of the 2₁ helix of galacturonan. The viscometric results in water showed that the 3₁ helix is capable of forming longer rheologically cooperative units compared with the 2₁ helix. Extrapolation to infinite ionic strength confirmed that, once all electrostatic interactions are cancelled, the elongation of the two helical forms is practically the same. At the same time, however, they indicated that the flexibility of the two-fold helix is more than fifteen times larger than that of the three-fold one. The result is nicely corroborated by a critical revisiting of ²³Na relaxation experiments. Full article

The syntheses of new neutral square-planar pyridine di-imine rhodium and iridium complexes with O- and S-donor (OH, OR, SH, SMe and SPh) ligands along with analogous cationic compounds are reported. Their crystal and electronic structures are investigated in detail with a focus on the non-innocence/innocence of the PDI ligand. The oxidation states of the metal centers were analyzed by a variety of experimental (XPS and XAS) and theoretical (LOBA, EOS and OSLO) methods. The dπ-pπ interaction between the metal centers and the π-donor ligands was investigated by theoretical methods and revealed the partial multiple-bond character of the M-O,S bonds. Experimental support is provided by a sizable barrier for the rotation about the Ir-S bond in the methyl thiolato complex and confirmed by DFT and LNO-CCSD(T) calculations. This was corroborated by the high Ir-O and Ir-S bond dissociation enthalpies calculated at the PNO-CCSD(T) level. Full article

Fluoroborane-type molecules (R¹R²B–F) are of interest in synthetic chemistry, but to date, apart from a handful of small species (such as H₂BF, HBF₂, and BF₃), little is known concerning the effect of substituents in governing the strength of the B–F bonds of such species toward homolytic dissociation in the gas phase. In this study, we have calculated the bond dissociation enthalpies (BDEs) of thirty unique B–F bonds at the CCSD(T)/CBS level using the high-level W1w thermochemical protocol. The B–F bonds in all species considered are very strong, ranging from 545.9 kJ mol⁻¹ in (H₂B)₂B–F to 729.2 kJ mol⁻¹ HBF₂. Nevertheless, these BDEs still vary over a wide range of 183.3 kJ mol⁻¹. The structural properties that affect the BDEs are examined in detail, and the homolytic BDEs are rationalized based on molecule stabilization enthalpies and radical stabilization enthalpies. Since polar B–F bonds may represent a challenging test case for density functional theory (DFT) methods, we proceed to examine the performance of a wide range of DFT methods across the rungs of Jacob′s Ladder for their ability to compute B–F BDEs. We find that only a handful of DFT methods can reproduce the CCSD(T)/CBS BDEs with mean absolute deviations (MADs) below the threshold of chemical accuracy (i.e., with average deviations below 4.2 kJ mol⁻¹). The only functionals capable of achieving this feat were (MADs given in parentheses): ωB97M-V (4.0), BMK (3.5), DSD-BLYP (3.8), and DSD-PBEB95 (1.8 kJ mol⁻¹). Full article

In this work, we considered the influence of viscogenic agents (glycerol, sucrose) as well as the temperature on the fluorescent characteristics of fluorescein at pH 6.5 in order to describe the acid-base status of local environment in terms of a spectrally detectable dianion-anion equilibrium. The protolytic equilibrium of fluorescein was found to depend on the solvent viscosity in a complex way. Whereas in the presence of sucrose the ratiometric signal of fluorescein (I⁴⁸⁸/I⁴³⁵) remains rather unchanged, the addition of glycerol (up to 40% w/w) results in the increase of the signal (up to 19%), that can be attributed to the different mechanisms of cosolvents effects on dye molecules in the ground state. Molecular dynamics of the dye in the presence of glycerol and sucrose revealed that the cosolvents preferentially interact with fluorescein monoanion and dianion, displacing water molecules from the local environment which in turn reduces the average number of the hydrogen bonds between xanthene ring of the dye and water molecules. The ratiometric signal demonstrates linear growth with the temperature in the range of 10–80 °C regardless of the presence of viscogenic agents. A linear correlation between the temperature sensitivity of the ratiometric signal and the change in the molar enthalpy of the proton dissociation reaction in buffer and viscous media was determined. Full article

Based on the data of the gas electron diffraction/mass spectrometry (GED/MS) experiment, the composition of the vapor over rhenium tetrafluoride at T = 471 K was established, and it was found that species of the Re₂F₈ is present in the gas phase. The geometric structure of the Re₂F₈ molecule corresponding to D_4h symmetry was found, and the following geometric parameters of the r_h1 configuration were determined: r_h1(Re-Re) = 2.264(5) Å, r_h1(Re-F) = 1.846(4) Å, α(Re-Re-F) = 99.7(0.2)°, φ(F-Re-Re-F) = 2.4 (3.6)°. Calculations by the self-consistent field in full active space approximation showed that for Re₂F₈, the wave function of the ¹A_1g ground electronic state can be described by the single closed-shell determinant. For that reason, the DFT method was used for a structural study of Re₂X₈ molecules. The description of the nature of the Re-Re bond was performed in the framework of Atom in Molecules and Natural Bond Orbital analysis. The difference in the experimental values of r(Re-Re) in the free Re₂F₈ molecule and the [Re₂F₈]²⁻ dianion in the crystal corresponds to the concept of a triple σ²π⁴ (Re^IV-Re^IV) bond and a quadruple σ²π⁴δ² (Re^III-Re^III) bond, respectively, which are formed between rhenium atoms due to the interaction of d-atomic orbitals. The enthalpy of dissociation of the Re₂F₈ molecular form in two monomers ReF₄ (Δ_dissH°(298) = 109.9 kcal/mol) and the bond energies E(Re-Re) and E(Re-X) in the series Re₂F₈→Re₂Cl₈→Re₂Br₈ molecules were estimated. It is shown that the Re-Re bond energy weakly depends on the nature of the halogen, while the symmetry of the Re₂Br₈ (D_4d) geometric configuration differs from the symmetry of the Re₂F₈ and Re₂Cl₈ (D_4h) molecules. Full article

It is an arduous and meaningful challenge to design and develop new energetic materials with lower sensitivity and higher energy. How to skillfully combine the characteristics of low sensitivity and high energy is the key problem in designing new insensitive high-energy materials. Taking a triazole ring as a framework, a strategy of N-oxide derivatives containing isomerized nitro and amino groups was proposed to answer this question. Based on this strategy, some 1,2,4-triazole N-oxide derivatives (NATNOs) were designed and explored. The electronic structure calculation showed that the stable existence of these triazole derivatives was due to the intramolecular hydrogen bond and other interactions. The impact sensitivity and the dissociation enthalpy of trigger bonds directly indicated that some compounds could exist stably. The crystal densities of all NATNOs were larger than 1.80 g/cm³, which met the requirement of high-energetic materials for crystal density. Some NATNOs (9748 m/s for NATNO, 9841 m/s for NATNO-1, 9818 m/s for NATNO-2, 9906 m/s for NATNO-3, and 9592 m/s for NATNO-4) were potential high detonation velocity energy materials. These study results not only indicate that the NATNOs have relatively stable properties and excellent detonation properties but also prove that the strategy of nitro amino position isomerization coupled with N-oxide is an effective means to develop new energetic materials. Full article

N-hydroxyimides are widely known as organocatalysts for aerobic oxidation and oxidative coupling reactions, in which corresponding imide-N-oxyl radicals play the role of catalytically active hydrogen atom abstracting species. The drawbacks of many N-hydroxyimides are poor solubility in low polarity solvents and limited activity in the cleavage of unactivated C–H bonds. To overcome these shortcomings, we have synthesized a new lipophilic N-hydroxyimide, 5,8-di-tert-butyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione, with high solubility in low-polarity solvents such as DCM. According to the EPR study, the stability of the corresponding imide-N-oxyl radical is comparable to that of the non-tert-butylated analogue, naphthalimide-N-oxyl radical. DFT calculations showed that the NO–H bond dissociation enthalpy (BDE) in the synthesized tert-butylated-N-hydroxynaphthalimide is one of the highest in N-hydroxyimide series, which corresponds to high hydrogen atom abstracting reactivity and may be useful in catalysis of strong C–H bond oxidative cleavage. The synthesized compound can be considered as catalyst for liquid-phase free-radical oxidation and oxidative coupling reactions in non-polar media where solubility was previously the limiting factor. Full article