Palladium(II)-catalyzed annulation of N-methoxy amides and arynes: computational mechanistic insights and substituents effects.

CONTEXT: The combined use of transition metal-catalyzed C-H activation with aryne annulation reactions has emerged as an important strategy in organic synthesis. In this study, the mechanisms of the palladium(II)-catalyzed annulation reaction of N-methoxy amides and arynes were computationally investigated by density functional theory. The role of methoxy amide as a directing group was elucidated through the calculation of three different pathways for the C-H activation step, showing that the pathway where amide nitrogen acts as a directing group is preferable. At the reductive elimination transition state, an unstable seven-membered ring is formed preventing the lactam formation. A substituent effect study based on an NBO analysis, Hammet, and using a More O'Ferall-Jenks plot indicates that the C-H activation step proceeds via an electrophilic concerted metalation-deprotonation (eCMD) mechanism. The results show that electron-withdrawing groups increase the activation barrier and contribute to an early Pd-C bond formation and a late C-H bond breaking when compared with electron-donating substituents. Our computational results are in agreement with the experimental data provided in the literature. METHODS: All calculations were performed using Gaussian 16 software. Geometry optimizations, frequency analyses at 393.15 K, and IRC calculations were conducted at the M06L/Def2-SVP level of theory. Corrected electronic energies, NBO charges, and Wiberg bond indexes were computed at the M06L/Def2-TZVP//M06L/Def2-SVP level of theory. Implicit solvent effects were considered in all calculations using the SMD model, with acetonitrile employed as the solvent.

Deciphering the irradiation induced fragmentation-rearrangement mechanisms in valence ionized CF3CH2F.

The increasing presence of 1,1,1,2-tetrafluoroethane (CF3CH2F) in the atmosphere has prompted detailed studies into its complex photodissociation behavior. Experiments focusing on CF3CH2F irradiation have unveiled an array of ions, with the persistent observation of the rearrangement product CHF2+ not yet fully understood. In this work, we combine density functional theory, coupled-cluster calculations with a complete basis set formalism, and atom-centered density matrix propagation molecular dynamics to investigate the energetics and dynamics of different potential pathways leading to CHF2+. We found that the two-body dissociation pathway involving an HF rearrangement, which was previously considered complex for CHF2+ formation, is actually straightforward but not likely due to the facile loss of HF. In contrast, our calculations reveal that the H elimination pathway, once thought of as a potential route to CHF2+, is not only comparably disadvantageous from both thermodynamic and kinetic points of view but also does not align with experimental data, particularly the lack of a rebound peak at m/z 101-102. We establish that the formation of CHF2+ is predominantly via the HF elimination channel, a conclusion experimentally corroborated by studies involving the trifluoroethylene cation CF2CHF+, a key intermediate in this process.

Determination of the lactose content in low-lactose milk using Fourier-transform infrared spectroscopy (FTIR) and convolutional neural network.

Demand for low lactose milk and milk products has been increasing worldwide due to the high number of people with lactose intolerance. These low lactose dairy foods require fast, low-cost and efficient methods for sugar quantification. However, available methods do not meet all these requirements. In this work, we propose the association of FTIR (Fourier Transform Infrared) spectroscopy with artificial intelligence to identify and quantify residual lactose and other sugars in milk. Convolutional neural networks (CNN) were built from the infrared spectra without preprocessing the data using hyperparameter adjustment and saliency map. For the quantitative prediction of the sugars in milk, a regression model was proposed, while for the qualitative assessment, a classification model was used. Raw, pasteurized and ultra-high temperature (UHT) milk was added with lactose, glucose, and galactose in six concentrations (0.1-7.0 mg mL-1) and, in total, 432 samples were submitted to convolutional neural network. Accuracy, precision, sensitivity, specificity, root mean square error, mean square error, mean absolute error, and coefficient of determination (R2) were used as evaluation parameters. The algorithms indicated a predictive capacity (accuracy) above 95% for classification, and R2 of 81%, 86%, and 92% for respectively, lactose, glucose, and galactose quantification. Our results showed that the association of FTIR spectra with artificial intelligence tools, such as CNN, is an efficient, quick, and low-cost methodology for quantifying lactose and other sugars in milk.

Kinetic and thermodynamic investigations on the HF elimination reactions from neutral and ionized CF3CH2F.

This work discusses the possible HF formation routes via recombination reactions from CF3CH2F (R-134a) and its cation. The molecular properties of the main reagents were first evaluated at the M06-2X/cc-pVTZ level. Then, changes in energy (ΔE) for all reactions comprising a possible HF formation from the studied systems were evaluated at the CCSD(T)/CBS//M06-2X/cc-pVTZ level. With the aid of Intrinsic Reaction Coordinate (IRC) calculations for each path, it is found that the HF formation reaction takes place majorly through the "1,2" elimination, resulting in an olefin as the secondary product. In turn, the IRC associated with "2,2" reactions allowed to find a post-barrier complex between the carbene :CHCF3 and HF in its exit channel, with dissociation energy of ∼4 kcal mol-1. Similarly, the cationic system exhibits favoritism towards the "1,2" elimination, and an ion-dipole post-barrier complex is found. The ΔE of such a complex production is negative in both directions, indicating this complex (25.5 kcal/mol more stable than CF3CH2F+) should be a minimum on the R-134a cation surface. However, unlike the neutral "2,2" path, there is no F atom migration transition state for the 2,2-HF elimination from CF3CH2F+. Hence, the F migration is expected to occur simultaneously with the rest of the structural changes towards the ion-dipole complex. The rate coefficients computed at the current level of theory, including corrections for anharmonicity and hindered rotations, showed a reasonable agreement with the available experimental data, inspiring confidence in our predictions for the cationic system.

Effectiveness of a new rutin Cu(II) complex in the prevention of lipid peroxidation and hepatotoxicity in hypercholesterolemic rats.

A new rutin copper(II) complex (R-Cu2) was prepared and characterized by spectroscopic methods and elemental analysis. The effects of rutin and R-Cu2 were evaluated on the prevention of hypercholesterolemia in animals feed with high-cholesterol diet (HCD) for 8 weeks. The animals (n = 5) were neither fed with HCD nor treated (control group), or were treated with vehicle, 10 mg/kg simvastatin, rutin (16 and 160 µmol/kg), and R-Cu2 (16 and 160 µmol/kg) administered orally. Total cholesterol (TC) levels were significantly increased (p < .01) in all HCD groups. In rutin and R-Cu2 groups, it was observed a discrete, but not significant, TC and LDL-induced increase inhibition compared with vehicle-treated group. R-Cu2 treatment significantly decreased (p < .05) plasma triglycerides compared with the vehicle-treated group. All groups receiving treatments maintained the malondialdehyde at normal levels. Serum NO levels were reduced in animals treated with rutin and R-Cu2 compared with the vehicle-treated group. In addition, the results also showed that the groups treated with rutin and R-Cu2 reduced significantly (p < .01), the number of neutrophils and prevented histological changes in all evaluated liver zones. R-Cu2 group maintained the ALT, AST, and ALP enzymes at normal levels. Thus, the effects of R-Cu2 in modulating inflammation and protecting liver damage were confirmed. PRACTICAL APPLICATIONS: Rutin, a plant-derived flavonoid, is one of phenolic compounds well known as a nutraceutical due to its antioxidant and anti-inflammatory properties. Findings of this study demonstrate the effects of both rutin and R-Cu2 in modulating inflammation and protecting liver damage in hypercholesterolemic rats. However, some effects analyzed became more evident in R-Cu2. Thereby, it was shown that the synthesis of a new flavonoid compound (R-Cu2) could be applied as a nutraceutical benefit option to prevent hypercholesterolemia condition.

Structure and electronic properties of azadirachtin.

We performed a combined DFT and Monte Carlo (13)C NMR chemical-shift study of azadirachtin A, a triterpenoid that acts as a natural insect antifeedant. A conformational search using a Monte Carlo technique based on the RM1 semiempirical method was carried out in order to establish its preferred structure. The B3LYP/6-311++G(d,p), wB97XD/6-311++G(d,p), M06/6-311++G(d,p), M06-2X/6-311++G(d,p), and CAM-B3LYP/6-311++G(d,p) levels of theory were used to predict NMR chemical shifts. A Monte Carlo population-weighted average spectrum was produced based on the predicted Boltzmann contributions. In general, good agreement between experimental and theoretical data was obtained using both methods, and the (13)C NMR chemical shifts were predicted highly accurately. The geometry was optimized at the semiempirical level and used to calculate the NMR chemical shifts at the DFT level, and these shifts showed only minor deviations from those obtained following structural optimization at the DFT level, and incurred a much lower computational cost. The theoretical ultraviolet spectrum showed a maximum absorption peak that was mainly contributed by the tiglate group.

Evisceração e enucleação na Faculdade de Medicina de Botucatu - UNESP: comparação entre duas décadas / Evisceration and enucleation in the UNESP Scholl of Medicine at Botucatu: a comparison of two decades

O objetivo deste estudo foi avaliar mudanças ocorridas no perfil dos pacientes e na conduta de remoção do bulbo ocular, comparando pacientes de duas décadas de atendimento. Foram avaliados, resptrospectivamente, 181 pacientes portadores de cavidade anoftálmica, operados na Facudade de Medicina de Botucatu (FMB) - UNESP. Os pacientes foram divididos em grupo G1, cuja cirurgia foi realizada entre os anos de 1979-1989 e G2, quando a cirurgia ocorreu entre 1990-2000. Foram estudados todos os indivíduos submetidos aos procedimento neste período, avaliando-se sexo, idade, causa da perda do bulbo ocular e tipo de cirurgia realizada(enucleação ou evisceração). Os dados foram submetidos à análise estatística segundo Teste de Goodman. Observou-se predomínio significativo de indivíduos na faixa etária entre 21-60 anos em ambos os grupos. O sexo masculino foi o mais ferqüentemente afetado no G1, enquanto no G2, não houve diferença entre os sexos. As causas de perda de bulbo ocular tiveram distribuição semelhante nos dois grupos, sendo as mais frqüentes phthisis bulbi, endoftalmite, glaucoma e trauma. A enucleação foi o procedimento significativamente mais indicados no G1, e a evisceração no G2. Em síntese, os dois grupos de pacientes foram semelhantes quanto à idade de acometimento e fatores causais que levaram a perda do olho; os grupos diferiram quanto ao sexo (preponderância do sexo masculino em G1 e semelhança entre os sexos em G2) e quanto ao tipo de cirurgia, sendo a evisceração a mais freqüente cirurgia realizada no G2.