Enhanced extraction of phenolic compounds from mango by-products using deep eutectic solvents.

Deep eutectic solvents (DESs) potential for the extraction of polyphenolic compounds (PC) from mango by-products (peel and seed) was evaluated. Ultrasound (US) and agitation were applied to evaluate the effects of solvent and extraction methodology. The extracts were characterized with antioxidant capacity and HPLC-DAD profile. A theoretical study was performed using density functional theory and the QTAIM approach. ß-alanine and choline chloride based DESs were effective to extract PC from peel and seed. Some DES increased PC extraction up to three times for peel (23.05 ± 1.22 mg/g DW) and up to five time for seeds (60.01 ± 1.40 mg/g DW). The PC profile varied with the solvent (DES vs EtOH/MeOH), procedure (US vs agitation) and material (peel or seed). Mangiferin extraction from peels was significantly increased with ß-alanine based DES (676.08 ± 20.34 µg/gDW). The strength of H-bonds had a determining effect on the viscosity of DESs. The solute-solvent solvation energy was suitable to estimate the strength of H-bond interactions between DES and target compounds. This study demonstrates the remarkable capacity of DESs to extract PC from mango by-products and provides insights into the factors controlling extraction properties.

Understanding the Fate of the Banert Cascade of Propargylic Azides: Sigmatropic versus Prototropic Pathway.

The Banert cascade is an efficient synthetic strategy for obtaining 4,5-disubstituted 1,2,3-triazoles. The reaction can proceed via a sigmatropic or prototropic mechanism depending on the substrate and the conditions. In this work, the mechanisms of both pathways from propargylic azides with different electronic features were investigated using density functional theory, quantum theory of atoms in molecules, and natural bond orbital approaches. The calculated energy barriers were consistent with the experimental data. Three patterns of electron density distribution on the transition structures were observed, which reflected the behaviors of the reactants in the Banert cascade. The stronger conjugative effects were associated with lower/higher free activation energies of sigmatropic/prototropic reactions, respectively. A clear relationship between the accumulation of the charge at the C3 atom of propargylic azides with the energy barriers for prototropic reactions was found. Thus, the obtained results would allow the prediction of the reaction's course by evaluating reactants.

Ability of Boron to Act as a Nucleophile and an Electrophile in Boryl Shift Reactions Unveiled by Electron Density Distribution Analysis.

The behavior of the tetracoordinate boron of N-methyliminodiacetic acid (MIDA) boronates as a nucleophile and an electrophile during the 1,2-boryl migration promoted by a Lewis acid and the 1,4-boryl migration promoted by a neighboring atom, respectively, have been investigated using density functional theory and the quantum theory of atoms in molecules. We found that when boron acts as a nucleophile, the electron density of the B-N interaction of the BMIDA moiety maintains the charge concentration over the boron atom, facilitating its transport toward the electron-deficient center. In this process, the BMIDA remains as a tetracoordinate. On the other hand, the B-N weakening generates a charge depletion region over the boron, allowing it to interact with the electron-rich center of O1, developing the boron atom, a pentacoordinate form. Then, the B-N bond breaking triggers a series of changes in the electronic structure of the boron atom. Our results explain the role of the MIDA ligand upon the remarkable susceptibility of the boron atom for switching its structural and electronic characteristics in the migration processes. In addition, the dichotomous behavior was evaluated with a different scenario, considering tricoordinate pinacol boronate as a boryl migrating group.

Insight into the factors controlling the equilibrium of allylic azides.

Several allylic azides with different double bond substitutions were studied to understand the factors, governing their equilibrium using density functional theory along with the quantum theory of atoms in molecules, non-covalent interactions and natural bond orbital approaches. The results showed that the hydroxyl group or heteroatoms in allylic azides interact with the molecule through an electrostatic weak interaction in each pair of regioisomers. The equilibrium shifts of substituted allylic azides, compared to non-substituted allylic azides, were not attributed to the presence of specific interactions, such as hydrogen bonds. The observed equilibrium shifts stemmed mainly from the strengthening and weakening of negative hyperconjugative interactions, which were affected by the weak interaction involving the proximal substituent in each regioisomer. A good linear correlation was obtained between the hyperconjugative energies of πC[double bond, length as m-dash]C→σ*Zb interactions and the calculated percentages of the secondary azide and tertiary azide in the equilibrium mixture. Also, the effect of the aromatic ring substituent was analysed using such approaches. This study not only provides insights into the factors controlling the stabilities of the substituted allylic azides, but also settles the basis to predict the regioisomer predominance in the equilibrium mixture.

Theoretical Study of the BF3-Promoted Rearrangement of Oxiranyl N-Methyliminodiacetic Acid Boronates.

The mechanism of the rearrangement of oxiranyl N-methyliminodiacetyl (MIDA) boronates in dicholoromethane has been extensively investigated with density functional theory. Several reaction pathways were examined. Our results revealed that the most-favorable mechanisms for the BF3-promoted rearrangement of 2-phenyl oxiranyl MIDA boronate (1) and 1-phenyl oxiranyl MIDA boronate (24) comprise two steps: ring opening of the epoxide to a carbocation intermediate followed by migration of a MIDA-boryl group (for the reaction of 1) and hydrogen (for the reaction of 24), to give the same BF3-coordinated α-boryl aldehyde in both cases. The first step of the ring opening of the epoxide is the rate-determining step of these reactions. In the rearrangement step for the reaction of 1, the MIDA-boryl group migrates easily, probably because of its electron-rich sp3-hybridized boron center. For 24, the most-favorable pathway involves a rare boryl-substituted carbocation. The course of these reactions is mainly controlled by electronic effects, although steric effects are also significant. The higher energy barrier calculated for the unsubstituted oxiranyl MIDA boronate (31) explains the lack of reactivity in the studied BF3-promoted rearrangement.

Reactivity and selectivity of boron-substituted alkenes in the Diels-Alder reaction with cyclopentadiene. A study of the electron charge density and its Laplacian.

The effect of the nature of the boron moiety upon the reactivity and the selectivity of a variety of vinylboron dienophiles (1-12) in the Diels-Alder (DA) reaction was investigated using density functional theory and the quantum theory of atoms in molecules. The calculated reactivity of the dienophiles decreases in the order vinylborane (1) > dihalovinylboranes (2-4) > dialkylvinylboranes (5-7) ≈ vinyl boronic acid (8) > vinylboronates (9, 10) > vinyl MIDA boronate (11) ≈ vinyltrifluoroborate (12). The DA reactions of 1-7 were slightly endo-selective due to the stronger C6-B secondary orbital interaction in the endo transition structures (TSs) evaluated by the C6|B delocalization index. In the TSs of 5 and 7, a combination of electronic and steric factors reduce the endo selectivity. The moderate exo selectivity calculated for the DA reactions of boronates 8-11 was attributed mainly to the hydrogen bond between the oxygen atom of boronate moieties and one of the acidic hydrogens of the methylene of cyclopentadiene in the exo TSs, which also reduces the ability of the oxygen lone pairs to donate electron density into the vacant boron orbital. Interestingly, the cooperative effect between the two hydrogen bonds in the exo TS of the DA reaction of vinyltrifluoroborate (12) determines the almost exclusive exo selectivity predicted for this DA reaction. We propose that the relative reactivities of the dienophiles can be estimated by the charge density (ρr) and its Laplacian (∇(2)ρr) at the (3,+1) critical point in the topology of ∇(2)ρr, evaluated at the reactant molecules in the ground state. The profiles of the several topological parameters along the reaction are affected by the nature of the substituents attached to the boron atom and by the mode of addition (endo and exo) in the DA reactions.

[4 + 3] and [4 + 2] mechanisms of the Diels-Alder reactions of vinylboranes: an analysis of the electron charge density distribution.

The Diels-Alder (DA) reactions of isoprene with vinylborane, dimethylvinylborane and dichlorovinylborane have been studied using density functional theory and the quantum theory of atoms in molecules. We evaluated the topological properties of the transition structures (TSs) and the evolution of such properties along the reaction paths. In accordance with previous studies, our results indicate that the endo TSs of the reaction with vinylborane present high [4 + 3] character, while the exo TSs and all the TSs of the reactions with dimethylvinylborane and dichlorovinylborane have [4 + 2] character. The higher charge concentration between the diene and the dienophile appears to account for the greater stabilization of the [4 + 3] TSs. The [4 + 3] structure turns into the [4 + 2] structure through a conflict mechanism in which the C1 and B atoms compete to become attached to C6. The C6-B interaction, present from early steps of the reaction until beyond the TSs, plays a key role in facilitating the formation of the new σ-bonds. The [4 + 3] and [4 + 2] mechanisms for the DA reactions of boron-substituted dienophiles may be distinguished by analyzing the profile of the ellipticity at the C1-C6 bcp along the course of the reaction.

Preferential formation of the different hydrogen bonds and their effects in tetrahydrofuran and tetrahydropyran microhydrated complexes.

The role of cycloether-water (c-w) and water-water (w-w) hydrogen bonds (H-bonds) on the stability of the tetrahydrofuran THF/(H(2)O)(n) and the tetrahydropyran THP/(H(2)O)(n) complexes with n = 1-4 was investigated herein using the density functional and ab initio methods and the atoms in molecules theory. Geometry optimizations for these complexes were carried out with various possible initial guess structures. It was revealed that the major contributions of the mono and dihydrated complexes came from c-w H-bonds. A competition between c-w and w-w H-bonds contribution was observed for trihydrated complexes. For most of tetrahydrated complexes, the inter-water H-bonds provided the greatest contribution, whereas the c-w contributions were small but not negligible. It was confirmed that to produce a hydrophobic hydration of cycloethers, the C-H···O(w) H-bond should be associated with a network of H-bonds that connects both portions of the solute, through the formation of a bifunctional H-bond. A linear correlation is obtained for the sum of electron density at the bond critical points (ρ(b)) with the interaction energy (ΔE) and with the solute-solvent interaction energy (ΔE(s-w)) of the microhydrated complexes. In addition, a new way to estimate the energetic contribution as well as the preferential formation of the different H-bonds based completely on ρ(b) was found. Even more, it allows to differentiate the contribution from c-w interactions in both hydrophilic and hydrophobic contributions, it is therefore a useful tool for studying the hydration of large biomolecules. The analysis of the modifications in the atomic and group properties brought about by successive addition of H(2)O molecules allowed to pinpoint the atoms or molecular groups that undergo the greatest changes in electron population and energetic stabilization. It was identified that the remarkable stabilization of the water oxygen atoms is crucial for the stabilization of the complexes.

Bifunctional hydrogen bonds in monohydrated cycloether complexes.

In this work, the cooperative effects implicated in bifunctional hydrogen bonds (H-bonds) were studied (in monohydrated six-membered cycloether) within the framework of the atoms in molecules (AIM) theory and of the natural bond orbitals (NBO) analysis. The study was carried out in complexes formed by six-membered cycloether compounds (tetrahydropyrane, 1,4-dioxane, and 1,3-dioxane) and a water molecule. These compounds were used as model systems instead of more complicated molecules of biological importance. All the results were obtained at the second-order Møller-Plesset (MP2) level theory using a 6-311++G(d,p) basis set. Attention was focused on the indicators of the cooperative effects that arise when a water molecule interacts simultaneously with a polar and a nonpolar portion of a six-membered cycloether (via bifunctional hydrogen bonds) and compared with conventional H-bonds where the water molecule only interacts with the polar portion of the cycloether. Different indicators of H-bonds strength, such as structural and spectroscopic data, electron charge density, population analysis, hyperconjugation energy and charge transference, consistently showed significant cooperative effects in bifunctional H-bonds. From the AIM, as well as from the NBO analysis, the obtained results allowed us to state that in the monohydrated six-membered cycloether, where the water molecule plays a dual role, as proton acceptor and proton donor, a mutual reinforcement of the two interactions occurs. Because of this feature, the complexes engaged by bifunctional hydrogen bonds are more stabilized than the complexes linked by conventional hydrogen bonds.

Topological analysis of aromatic halogen/hydrogen bonds by electron charge density and electrostatic potentials.

In this work, the intermolecular distribution of the electronic charge density in the aromatic hydrogen/halogen bonds is studied within the framework of the atoms in molecules (AIM) theory and the molecular electrostatic potentials (MEP) analysis. The study is carried out in nine complexes formed between benzene and simple lineal molecules, where hydrogen, fluorine and chlorine atoms act as bridge atoms. All the results are obtained at MP2 level theory using cc-pVTZ basis set. Attention is focused on topological features observed at the intermolecular region such as bond, ring and cage critical points of the electron density, as well as the bond path, the gradient of the density maps, molecular graphs and interatomic surfaces. The strength of the interaction increases in the following order: F[Symbol: see text]pi < Cl[Symbol: see text]pi < H[Symbol: see text]pi. Our results show that the fluorine atom has the capability to interact with the pi-cloud to form an aromatic halogen bond, as long as the donor group is highly electron withdrawing. The Laplacian topology allows us to state that the halogen atoms can act as nucleophiles as well as electrophiles, showing clearly their dual character.