RESUMO

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.

RESUMO

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).

RESUMO

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.

RESUMO

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.

RESUMO

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.

Assuntos

Antimaláricos/síntese química , Antimaláricos/farmacologia , Compostos de Espiro/síntese química , Compostos de Espiro/farmacologia , Triterpenos/síntese química , Triterpenos/farmacologia , 17-alfa-Hidroxiprogesterona/farmacologia , Animais , Antimaláricos/química , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Resistência a Medicamentos , Células Hep G2 , Humanos , Concentração Inibidora 50 , Malária/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Parasitemia/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Compostos de Espiro/química , Triterpenos/química

RESUMO

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.

RESUMO

[reaction: see text] This study is a multinational, multidisciplinary contribution to the thermochemistry of dimethyl1,4-cubanedicarboxylate and the corresponding isomeric, cuneane derivative and provides both structural and thermochemical information regarding the rearrangement of dimethyl 1,4-cubanedicarboxylate to dimethyl 2,6-cuneanedicarboxylate. The enthalpies of formation in the condensed phase at T = 298.15 K of dimethyl 1,4-cubanedicarboxylate (dimethyl pentacyclo[4.2.0.0.(2,5)0.(3,8)0(4,7)]octane-1,4-dicarboxylate) and dimethyl 2,6-cuneanedicarboxylate (dimethyl pentacyclo[3.3.0.0.(2,4)0.(3,7)0(6,8)]octane-2,6-dicarboxylate) have been determined by combustion calorimetry, delta(f) H(o)m (cr)/kJ x mol(-1) = -232.62 +/- 5.84 and -413.02 +/- 5.16, respectively. The enthalpies of sublimation have been evaluated by combining vaporization enthalpies evaluated by correlation-gas chromatography and fusion enthalpies measured by differential scanning calorimetry and adjusted to T = 298.15 K, delta(cr) (g)Hm (298.15 K)/kJ x mol(-1) = 117.2 +/- 3.9 and 106.8 +/- 3.0, respectively. Combination of these two enthalpies resulted in delta(f) H(o)m (g., 298.15 K)/kJ x mol(-1) of -115.4 +/- 7.0 for dimethyl 1,4-cubanedicarboxylate and -306.2 +/- 6.0 for dimethyl 2,6-cuneanedicarboxylate. These measurements, accompanied by quantum chemical calculations, resulted in values of delta(f) Hm (g, 298.15 K) = 613.0 +/- 9.5 kJ x mol(-1) for cubane and 436.4 +/- 8.8 kJ x mol(-1) for cuneane. From these enthalpies of formation, strain enthalpies of 681.0 +/- 9.8 and 504.4 +/- 9.1 kJ x mol(-1) were calculated for cubane and cuneane by means of isodesmic reactions, respectively. Crystals of dimethyl 2,6-cuneanedicarboxylate are disordered; the substitution pattern and structure have been confirmed by determination of the X-ray crystal structure of the corresponding diacid.

RESUMO

Thermochemical data, and in particular the enthalpies of formation of oxygen- and sulfur-containing six-membered heterocycles provide essential information on the factors responsible for the contrasting behavior (structural, conformational and reactivity) between these types of compounds. A proper understanding of the experimental observations requires theoretical modeling in order to confirm the relative importance of the steric, electronic, electrostatic and stereoelectronic interactions that are responsible of the enthalpies of formation for the heterocyclic compounds of interest.

Assuntos

Simulação por Computador , Compostos Heterocíclicos/química , Compostos de Enxofre/química , Enxofre/química , Calorimetria/métodos , Estrutura Molecular

RESUMO

The enthalpies of combustion and vaporization of 3-buten-1-ol and 3-butyn-1-ol have been measured by static bomb combustion calorimetry and correlation gas chromatography techniques, respectively, and the gas-phase enthalpies of formation, Delta(f)H degrees (m)(g), have been determined, the values being -147.3 +/- 1.8 and 16.7 +/- 1.6 kJ mol(-1), for 3-buten-1-ol and 3-butyn-1-ol, respectively. High level calculations at the G2 and G3 levels have also been carried out. Relationships between the enthalpies of formation of 1-alkanols, 1-alkenols and 1-alkynols and with the corresponding hydrocarbons have been discussed. From the calculated contributions to Delta(f)H degrees (m)(g) for the substitutions of CH(3) by CH(2)OH, CH(3)CH(2) by CH(2)=CH and CH(3)CH(2) by CH triple bond C, we have estimated the Delta(f)H degrees (m)(g) values for 3-buten-1-ol and 3-butyn-1-ol, in excellent agreement with the experimental ones. Delta(f)H degrees (m)(g) values for 1-alkenols and 1-alkynols up to 10 carbon atoms have also been estimated.