Effect of temperature on the formation of acrylamide in cocoa beans during drying treatment: An experimental and computational study.

The aim of this work was to determine the effect of temperature on the formation of acrylamide in cocoa beans during drying treatment by an experimental and computational study, in order to assess the presence of this neoformed compound from postharvest stage. The computational study was conducted on the reaction between fructose, glyoxal from glucose, and on asparagine at the M06-2X/6-31+G(d,p) level, under cocoa bean drying conditions at 323.15 to 343.15 K. The proposed reaction for acrylamide formation consisted of seven steps, which required to progress a via cyclic transition state of the four members. In addition, step III (decarboxylation) was considered to be the rate-determining step. Glucose followed an E1-like elimination and fructose exhibited an E1cb-like elimination. Computational model showed that the reaction of acrylamide formation was favored by fructose rather than glucose. The content of reducing sugars, asparagine and acrylamide in fermented and dried cocoa from two subregions of Antioquia-Colombia, as well as roasted cocoa, were evaluated by UHPLC-C-CAD and UHPLC-QqQ. The concentrations of monosaccharides measured at the end of the fermentation and drying process of cocoa nibs showed greater decreases in the levels of fructose as compared to glucose, supporting the main model hypothesis. Acrylamide formation only occurred in Bajo Cauca due to the presence of both precursors and fast drying time (72 h). Finally, it was possible to find the conditions to which acrylamide can be formed from the drying process and not only from roasting, information that can be used for future control strategies.

Photoreduction of gaseous oxidized mercury changes global atmospheric mercury speciation, transport and deposition.

Anthropogenic mercury (Hg(0)) emissions oxidize to gaseous Hg(II) compounds, before deposition to Earth surface ecosystems. Atmospheric reduction of Hg(II) competes with deposition, thereby modifying the magnitude and pattern of Hg deposition. Global Hg models have postulated that Hg(II) reduction in the atmosphere occurs through aqueous-phase photoreduction that may take place in clouds. Here we report that experimental rainfall Hg(II) photoreduction rates are much slower than modelled rates. We compute absorption cross sections of Hg(II) compounds and show that fast gas-phase Hg(II) photolysis can dominate atmospheric mercury reduction and lead to a substantial increase in the modelled, global atmospheric Hg lifetime by a factor two. Models with Hg(II) photolysis show enhanced Hg(0) deposition to land, which may prolong recovery of aquatic ecosystems long after Hg emissions are lowered, due to the longer residence time of Hg in soils compared with the ocean. Fast Hg(II) photolysis substantially changes atmospheric Hg dynamics and requires further assessment at regional and local scales.

Density Functional Theory Computational Reexamination of the Anomeric Effect in 2-Methoxy- and 2-Cyano-1,3-dioxanes and 1,3-Dithianes. Stereoelectronic Interactions Involving the Cyano (C≡N:) Group Revealed by Natural Bond Orbital (NBO) Analysis.

This study reports DFT geometry optimization of the anancomeric (ring conformationally anchored) axial r2-methoxy- trans-4, trans-6-dimethyl- and r-2-cyano- trans-4, trans-6-dimethyl-1,3-dioxanes (1-ax and 3-ax, respectively), the equatorial isomers (2-eq and 4-eq, respectively), the axial r2-methoxy- and r2-cyano- trans-4, trans-6-dimethyl-1,3-dithianes (5-ax and 7-ax, respectively), and the equatorial isomers (6-eq and 8-eq, respectively). The computational results reproduce the anomeric effect in 1-8, and most importantly, Weinhold's NBO analysis supports the contribution of n(X) → σ*(C-Y) stereoelectronic interactions that stabilize the axial isomers. Furthermore, NBO analysis of delocalization energy E(2) of properly aligned filled/empty orbitals in these isomeric 2-polar-substituted heterocycles reveals that n(O) → σ*(C-Hax) is responsible for the increased charge density at C(2)-Hax in the equatorial isomers, providing an explanation for the computational observation that very recently led Wiberg, Bailey, Lambert, and Stempel ( J. Org. Chem. 2018, 83, 5242-5255) to discard a potential contribution of n(X) → σ*(C-Y) stereoelectronic interactions that stabilize the axial isomers. Interestingly, during the course of this study, two relevant stereoelectronic interactions involving the cyano group were revealed, n(N) → σ*(NC-C) and σ(C(2)-H) → σ*(C-N).

Stereoelectronic Interactions Exhibited by 1 JC-H One-Bond Coupling Constants and Examination of the Possible Existence of the Intramolecular α-Effect in Six-Membered Oxygen-Containing Heterocycles.

For more than five decades since its original conception, the α-effect has been advocated with arguments based on kinetic reactivity data. The present study was undertaken with the aim of gathering theoretical information on thermodynamic bond energy data in systems that could in principle give rise to intramolecular α-effects. In particular, oxygen-containing six-membered rings oxa-, 1,2-dioxa-, 1,3-dioxa-, 1,2,4-trioxa-, and 1,2,4,5-tetraoxacyclohexane were optimized at the B3LYP/aug-cc-pVTZ level of theory, and the magnitude of all C-H one-bond coupling constants was determined. Furthermore, hyperconjugative interactions were evaluated with Natural Bond Orbital analysis. Analysis of the collected information leads to the conclusion that ether oxygens are apparently better donors than peroxide oxygens; that is, the n(O) → σ*(C-Hax) two-orbital/two-electron interaction seems to be stronger than the n(O-O) → σ*(C-Hax) two-orbital/two-electron interaction, and this finding is contrary to expectations in terms of the α-effect.

Gas-Phase Acidities and Basicities of Alanines and N-Benzylalanines by the Extended Kinetic Method.

This paper reports an experimental determination of the gas-phase acidities and basicities of N-benzylalanines, in both their α and ß forms, by means of the extended kinetic method (EKM). The experimental gas-phase acidity of ß-alanine was also determined. Standard ab initio molecular orbital calculations at the G3 level were performed for alanines, and at the G3(MP2)//B3LYP level for N-benzylalanines. There is a very good agreement between the experimental and the calculated values. The more branched α-amino acids are more acidic and less basic than the linear ß-amino acids.

Stereoelectronic Interactions as a Probe for the Existence of the Intramolecular α-Effect.

The first systematic study of the intramolecular α-effect, both in the stable ground-state structures and in the high-energy intermediates, was accomplished using the anomeric effect as an internal stereoelectronic probe. Contrary to the expectations based on the simple orbital mixing model, the lone pairs in a pair of neutral directly connected heteroatoms are not raised in energy to become stronger donors toward adjacent σ- and π-acceptors. Instead, the key n(X-Y)→σ*C-F interactions (X,Y = O,N) in the "α-systems" (both acyclic and constrained within a heterocyclohexane frame) are weaker than nX→σ*C-F interactions in "normal" systems. Surprisingly, polar solvent effects increase the apparent magnitude of α-effect as measured via increase in the anomeric stabilization. This behavior is opposite to the solvent dependence of normal systems where the anomeric effect is severely weakened by polar solvents. This contrasting behavior reflects the different balance of electrostatic and conjugative interactions in the two types of anomeric systems: the α-systems suffer less from the unfavorable orientation of bond dipoles in the equatorial conformer, a destabilizing electrostatic effect that is shielded by the polar environments. A weak α-effect is brought to life when the buttressing α-heteroatom bears a negative charge. However, electrostatic components mask the role of stabilizing orbital interactions. In contrast, the increased electron demand in carbocations and related electron-deficient TS- like structures does not lead to activation of the α-effect. As a consequence, we observed that ethers are better radical- and cation-stabilizing groups than peroxides. The latter finding should have significant implications for understanding the mechanistic complexity associated with the interaction of carbonyl compounds with hydroperoxides and H2O2 in acidic media, as such reactions involve α-cationic intermediates.

An integral equation and simulation study of hydrogen inclusions in a molecular crystal of short-capped nanotubes.

In this work we have assessed the ability of a recently proposed three-dimensional integral equation approach to describe the explicit spatial distribution of molecular hydrogen confined in a crystal formed by short-capped nanotubes of C50 H10. To that aim we have resorted to extensive molecular simulation calculations whose results have been compared with our three-dimensional integral equation approximation. We have first tested the ability of a single C50 H10 nanocage for the encapsulation of H2 by means of molecular dynamics simulations, in particular using targeted molecular dynamics to estimate the binding Gibbs energy of a host hydrogen molecule inside the nanocage. Then, we have investigated the adsorption isotherm of the nanocage crystal using grand canonical Monte Carlo simulations in order to evaluate the maximum load of molecular hydrogen. For a packing close to the maximum load explicit hydrogen density maps and density profiles have been determined using molecular dynamics simulations and the three-dimensional Ornstein-Zernike equation with a hypernetted chain closure. In these conditions of extremely tight confinement the theoretical approach has shown to be able to reproduce the three-dimensional structure of the adsorbed fluid with accuracy down to the finest details.

Theoretical Evidence for the Relevance of n(F) → σ*(C-X) (X = H, C, O, S) Stereoelectronic Interactions.

Theoretical calculations on r-1,c-3,c-5-trifluorocyclohexane (1), r-2,c-4,c-6-trifluoro-1,3,5-trioxane (2), and r-2,c-4,c-6-trifluoro-1,3,5-trithiane (3) confirm the importance of n(F) → σ*(C-Y)gem, where Y = H, C, O, S, hyperconjugative interactions; that is, contrary to common wisdom, fluorine is a good lone pair electron donor toward geminal sigma bonds. This conclusion is in line with the recent observations reported by O'Hagan and co-workers, who synthesized and examined all-cis 1,2,3,4,5,6-hexafluoro-cyclohexane (Nat. Chem. 2015, 7, 483-488).

Ab initio quantum-chemical computations of the electronic states in HgBr2 and IBr: Molecules of interest on the Earth's atmosphere.

The electronic states of atmospheric relevant molecules IBr and HgBr2 are reported, within the UV-Vis spectrum range (170nm≤λphoton≤600 nm) by means of the complete-active-space self-consistent field/multi-state complete-active-space second-order perturbation theory/spin-orbit restricted-active-space state-interaction (CASSCF/MS-CASPT2/SO-RASSI) quantum-chemical approach and atomic-natural-orbital relativistic-correlation-consistent (ANO-RCC) basis sets. Several analyses of the methodology were carried out in order to reach converged results and therefore to establish a highly accurate level of theory. Good agreement is found with the experimental data with errors not higher than around 0.1 eV. The presented analyses shall allow upcoming studies aimed to accurately determine the absorption cross sections of interhalogen molecules and compounds with Hg that are relevant to better comprehend the photochemical processes taking place in the atmosphere.

Theoretical examination of the S-C-P anomeric effect.

Three decades after the discovery of a strong S-C-P anomeric effect in 2-diphenylphosphinoyl-1,3-dithiane (1) and 2-trimethylphosphonium-1,3-dithiane (4), its definitive interpretation is still lacking. The present study reports DFT geometry optimizations of 1-ax, 1-eq, 4-ax, and 4-eq, which do reproduce the S-C-P anomeric effect in 1 and 4, worth 5.45 and 3.08 kcal/mol, respectively (in chloroform solvent). Weinhold's NBO analysis supports the existence of dominant nX → σ*C-Y stereoelectronic interactions that stabilize the axial conformers.

Thermochemical insights on the conformational energetics of azepan and azepan-1-ylacetonitrile.

This paper is concerned with computational and experimental thermochemical studies of azepan and azepan-1-ylacetonitrile, molecules whose flexible ring structure provides several conformational forms with low energy barriers among them. The computational study describes the energetic analysis of the six most stable conformers on the potential energy surfaces and the determination of their gas-phase standard enthalpy of formation at the reference temperature of 298.15 K. The same gas-phase enthalpic parameters are also derived from the enthalpies of formation in the liquid phase and the enthalpies of vaporization, at T = 298.15 K, determined experimentally using the combustion calorimetry and the Calvet microcalorimetry techniques, respectively. The experimental data reported in this work for the two titled compounds together with other available in the literature for related molecules enabled the establishment of an increments scheme, providing a reliable approach on the prevision of gas-phase enthalpy of formation of cyclic/acyclic hydrocarbons and amines. Complementary, natural bond orbital (NBO) calculations were also performed, allowing an advance on the analysis of the structural and reactivity behavior of these type of compounds.

Thermodynamic and conformational study of proline stereoisomers.

Amino acids play fundamental roles both as building blocks of proteins and as intermediates in metabolism. Proline, one of the 20 natural amino acids, has a primordial function in enzymes, peptide hormones, and proteins. The energetic characterization of these molecules provides information concerning stability and reactivity and has great importance in understanding the activity and behavior of larger molecules containing these structures as fragments. In the present work, parallel experimental and computational studies have been performed. The experimental studies have been based on calorimetric and effusion techniques, from which the enthalpy of formation in the crystalline phase and the enthalpy of sublimation of the sterioisomers L-, D-, and the DL-mixture of proline have been derived. Additionally, vapor pressure measurements have also enabled the determination of the entropies and Gibbs energies of sublimation, at T = 298.15 K. From the former results, the experimental standard (p(o) = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, of L-proline, D-proline, and DL-proline have been calculated as -388.6 ± 2.3, -391.9 ± 2.0, and -391.5 ± 2.4 kJ·mol(-1), respectively. A computational study at the G3 and G4 levels has been carried out. Conformational analysis has been done and the enthalpy of formation of proline as well as other intrinsic properties such as acidity, basicity, adiabatic ionization enthalpy, electron and proton affinities, and bond dissociation enthalpies have been calculated. There is a very good agreement between calculated and experimental values, when they are available.

Isoelectronic and isolobal O, CH2, CH3+ and BH3 as electron pairs; similarities between molecular and solid-state chemistry.

A topological analysis of the electron localization function (ELF) of a molecule of hexamethyldisiloxane, (H3C)3-Si-O-Si-(CH3)3, has been carried out, drawing a consistent picture of Si-O-Si bonding both in the linear and angular geometries. The ELF analysis confirms the idea that the O atom, in the linear geometry of (H3C)3-Si-O-Si-(CH3)3, is isolobal with the isoelectronic -CH3(+)- and -BH3- groups, the bonding in the Si-O-Si group being described as a two-electron, three-center (2e, 3c) bond. At the same time, the three oxygen lone pairs mirror the three C-H and B-H bonds, respectively. On the contrary, in the angular geometry the same O atoms form two Si-O bonds and its lone pairs mimic the geometry of the -CH2- group. In this model the O atoms would play the same role as the formally present O(2-) anions in the `so-called' ionic solids, such as in the skeletons of aluminate and silicate polyanions, thereby connecting molecular and solid-state chemistry as formulated by the `fragment formalism' or the `molecular unit-cell approach'. This unifying concept as well as the calculations we have carried out fully agree and also give support to earlier ideas developed by Bragg and Bent, among other authors. Bonding in the series of compounds P4, P4O6, P4O10, N4(CH2)6 (hexamethylenetetramine) and (CH)4(CH2)6 (adamantane) is discussed in the context of the isolobal model.

Diosgenone synthesis, anti-malarial activity and QSAR of analogues of this natural product.

Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC50 27.9 µM vs. 10.1 µM, 2.9 µM and 11.3 µM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.

Intrinsic relative scales of electrophilicity and nucleophilicity.

The formulation of the second-order perturbation approach to the stabilization energy of the A-B interacting species due to charge transfer is revisited. Intrinsic (i.e., electronic) theoretical indices for both relative electrophilicity and nucleophilicity are proposed for any electrophile (A)-nucleophile (B) pairs of combining species. By using the new descriptors, an electronic analogue to the Mayr-Patz linear free relationship has been successfully tested in the context of available experimental evidence reported for reactions of primary and secondary amines with benzhydrylium ions.

Thermochemistry of uracils. Experimental and computational enthalpies of formation of 5,6-dimethyl-, 1,3,5-trimethyl-, and 1,3,5,6-tetramethyluracils.

We describe in the current paper an experimental and computational study of three methylated uracils, in particular, the 5,6-dimethyl-, 1,3,5-trimethyl-, and 1,3,5,6-tetramethyl derivatives. The values of the standard (p(0) = 0.1 MPa) molar enthalpies of formation in the gas phase at T = 298.15 K have been determined. The energies of combustion were measured by static bomb combustion calorimetry, and from the results obtained, the standard molar enthalpies of formation in the crystalline state at T = 298.15 K were calculated. The enthalpies of sublimation were determined using the transpiration method in a saturated N(2) stream. Values of -(376.2 ± 2.6), -(355.9 ± 3.0), and -(381.7 ± 2.8) kJ·mol(-1) for the gas-phase enthalpies of formation at T = 298.15 K of 5,6-dimethyluracil, 1,3,5-trimethyluracil, and 1,3,5,6-tetramethyluracil, respectively, were obtained from the experimental thermochemical study. An extended theoretical study with the G3 and the G4 quantum-chemical methods has been carried out for all the possible methylated uracils. There is a very good agreement between experimental and calculated enthalpies of formation for the three derivatives studied. A Free-Wilson analysis on G4-calculated enthalpies of formation has been carried out, and the contribution of methylation in the different positions of the uracil ring has been estimated.

Substituent effects on the thermochemistry of thiophenes. a theoretical (G3(MP2)//B3LYP and G3) study.

Very good linear correlations between experimental and calculated enthalpies of formation in the gas phase (G3(MP2)//B3LYP and G3) for 48 thiophene derivatives have been obtained. These correlations permit a correction of the calculated enthalpies of formation in order to estimate more reliable "experimental" values for the enthalpies of formation of substituted thiophenes, check the reliability of experimental measurements, and also predict the enthalpies of formation of new thiophenes that are not available in the literature. Moreover, the difference between the enthalpies of formation of isomeric thiophenes with the same substituent in positions 2 and 3 of the ring has been analyzed. Likewise, a comparison of the substituent effect in the thiophene and benzene rings has been established.

Experimental and computational thermochemical study of 2-thiobarbituric acid: structure-energy relationship.

This paper reports an experimental and computational thermochemical study on 2-thiobarbituric acid (2-thioxodihydropyrimidine-4,6(1H,5H)-dione), [CAS 504-17-6]. The value of the standard (p(0) = 0.1 MPa) molar enthalpy of formation in the gas phase at T = 298.15 K has been determined. The energy of combustion was measured by bomb combustion calorimetry, using a rotatory bomb, and from the result obtained, the standard molar enthalpy of formation in the crystalline state at T = 298.15 K was calculated as -(396.8 ± 0.9) kJ·mol(-1). The enthalpy of sublimation was determined using a transference (transpiration) method in a saturated N(2) stream and a value of the enthalpy of sublimation at T = 298.15 K was derived as (118.3 ± 2.2) kJ·mol(-1). From these results a value of -(278.5 ± 2.4) kJ·mol(-1) for the gas-phase enthalpy of formation at T = 298.15 K was determined. Theoretical calculations at the G3 and G4 levels were performed, and a study of the molecular and electronic structure of the compound has been carried out. Calculated enthalpies of formation are in very good agreement with the experimental value.