Revealing the Role of Noncovalent Interactions on the Conformation of the Methyl Group in Tricyclic Orthoamide.

Tricyclic orthoamides are valuable molecules with wide-ranging applications, including organic synthesis and molecular recognition. Their structural properties make them intriguing, particularly the eclipsed all-trans conformer, which is typically less stable than the alternated conformation and is a rare phenomenon in organic chemistry. However, it gains stability in crystalline and hydrated settings, challenging the existing theoretical explanations. This study investigates which factors make eclipsed conformers more stable using experimentally reported anhydrous (ATO) and hydrated (HTO) crystal structures. Employing the quantum theory of atoms in molecules, noncovalent interaction index, and pairwise energy decomposition analysis, we delve into the noncovalent interaction environment surrounding the molecule of interest. In ATO, dispersive interactions dominate, whereas in HTO, both dispersive and electrostatic contributions are observed due to the presence of water molecules. Anchored to the lone pairs of the nitrogen atom in the orthoamide tricycle, water molecules prompt the methyl group's eclipsing through intermolecular and intramolecular interactions. This work resolves the long-standing conflict behind why tricyclic orthoamide has an eclipsed conformation by establishing the stabilization factors. These insights have implications for crystal engineering and design, enhancing our understanding of structural behavior in both crystalline and hydrated environments.

Stereoelectronic interactions are too weak to explain the molecular conformation in solid state of cis-2-tert-butyl-5-(tert-butylsulfonyl)-1,3-dioxane.

cis-2-tert-Butyl-5-(tert-butylsulfonyl)-1,3-dioxane (cis-1) exhibits a high degree of eclipsing in the H-C5-S-C segment in the solid state, the origin of which remains unexplained. The eclipsed conformation that corresponds to an energetic minimum in the solid state practically corresponds to a rotational transition state in solution, which allows an approach to understand transitions states. The difference in the enthalpy of sublimation ΔsubH between cis-1 and the more stable trans-1 is 8.40 kcal mol-1, lets to consider that the intermolecular interactions in the crystalline structure must be responsible for the conformational effect observed in the solid state. The study of the experimental electron density of cis-1 in solid state allowed to establish that CH⋯OS intermolecular interaction is the main contribution to the observed eclipsing. The charge density analysis was also performed using the quantum theory of atoms in molecules to evaluate the nature and relevance of the intermolecular interactions in the crystal structure.

Effect of the nO → π*C═O Interaction on the Conformational Preference of 1,3-Diketones: A Case Study of Riolozatrione Derivatives.

The cyclopropane ring-opening reaction of riolozatrione, a natural product obtained from Jatropha dioica, afforded a 2,2-disubstituted 1,3-cyclohexandione displaying an alkyl methyl ether group at position 5. The conformational analysis of this product showed a high preference for the trans-diaxial conformation in both solution and solid state. Such conformation was possible from the noncovalent intramolecular nX → π*C═O interactions (X = an element having an unshared electron pair), allowing the determination of the interaction energies. Since the nX → π*C═O interactions can be regarded as additive, the energy values ranged from 4.52 to 6.51 kcal mol-1 for each carbonyl group with a strong dependency on the interatomic distances. The rigorous analysis of the electron density in the topological theory of atoms in molecules framework clearly shows that the origin of O-C═O interactions are through the nO → π*C═O electron transfer mechanism. Such interactions are slightly weaker than a canonical hydrogen bond but seemingly stronger than a van der Waals interaction. This interaction must be considered as a stereoelectronic effect due the electronic transfer between the interacting groups, which are limited by their relative stereochemistry and can be represented by a bond-no bond interaction, causing the pyramidalization of the carbonyl, which is the charge acceptor group.

[Quality care indicators for neonates with selected pathologies: pilot study.] / Indicadores de calidad de la atención a neonatos con patologías seleccionadas: estudio piloto.

OBJECTIVE: Develop and pilot indicators of quality of care to neonates with relevant conditions in Mexico (prematurity, neonatal sepsis, perinatal asphyxia, and intrauterine hypoxia). MATERIALS AND METHODS: Own indicators were built based on key recommendations of national clinical practice guidelines and indicators found in international repositories. With previous search, selection and prioritization, the indicators were piloted within two hospitals. The feasibility of measuring, (kappa index) reliability and usefulness was analyzed to detect quality problems. RESULTS: 23 indicators were selected and piloted, 12 are compounds, of the total, nine were feasible and reliable. The quality of the hospital's information was diverse and often poor, limiting both the feasibility and the reliability of the indicators. Improvement opportunities were identified thorough the compliance levels. CONCLUSIONS: A set of nine indicators valid, reliable, feasible and useful indicators is proposed in order to monitor the quality of care of pathological neonates.

OBJETIVO: Desarrollar y pilotar indicadores de calidad de la atención a neonatos con padecimientos relevantes en México (prematuridad, sepsis neonatal, asfixia perinatal e hipoxia intrauterina). MATERIAL Y MÉTODOS: Se construyeron indicadores propios a partir de recomendaciones clave de las guías de práctica clínica nacionales e indicadores encontrados en repositorios internacionales. Previa búsqueda, selección y priorización, los indicadores fueron pilotados en dos hospitales. Se analizó la factibilidad de medición, fiabilidad (índice kappa) y utilidad para detectar problemas de calidad. RESULTADOS: Se seleccionaron y pilotaron 23 indicadores; 12 eran compuestos. Del total, nueve fueron factibles y fiables. La calidad de la información en los hospitales fue diversa y frecuentemente deficiente, limitando tanto la factibilidad como la fiabilidad de los indicadores. Los niveles de cumplimiento identificaron oportunidades de mejora. CONCLUSIONES: Se propone un set de nueve indicadores válidos, factibles, fiables y útiles para la monitorización de la calidad en la atención a neonatos patológicos.

Stereochemistry of a Second Riolozane and Other Diterpenoids from Jatropha dioica.

The dichloromethane extract of the roots of Jatropha dioica afforded riolozatrione (1) and a C-6 epimer of riolozatrione, 6-epi-riolozatrione (2), as a new structure and only the second reported riolozane diterpenoid. The two known diterpenoids jatrophatrione (3) and citlalitrione (4) were also isolated and characterized. Both epimers 1 and 2 are genuine plant constituents, with 2 likely being the biosynthesis precursor of 1 due to the tendency for the quantitative transformation of 2 into 1 under base catalysis. The structural characterization and distinction of the stereoisomers utilized 1H iterative full-spin analysis, yielding complete J-correlation maps that were represented as quantum interaction and linkage tables. The absolute configuration of compounds 1-4 was established by means of vibrational circular dichroism and via X-ray diffraction analysis for 1, 2, and 4. Additionally, the cytotoxic and antiherpetic in vitro activities of the isolates were evaluated.

The influence of sulfur configuration in 1 H NMR chemical shifts of diasteromeric five-membered cyclic sulfites.

The effect of the stereochemistry of the sulfur atom on 1 H chemical shifts of the diasteromeric pair of cyclic sulfites of 4-[methoxy(4-nitrophenyl)methyl]-5-phenyl-1,3,2-dioxathiolan-2-oxide was investigated. The complete 1 H and 13 C NMR spectral assignment was achieved by the use of one-dimensional and two-dimensional NMR techniques in combination with X-ray data. A correlation of experimental data with theoretical calculations of chemical shift tensors using density functional theory and topological theory of atoms in molecules was made. Copyright © 2016 John Wiley & Sons, Ltd.

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes.

It has been proposed that elemanes are biogenetically formed from germacranes by Cope sigmatropic rearrangements. Normally, this reaction proceeds through a transition state with a chair conformation. However, the transformation of schkuhriolide (germacrane) into elemanschkuhriolide (elemane) may occur through a boat transition state due to the final configuration of the elemanschkuhriolide, but this transition state is questionable due to its high energy. The possible mechanisms of this transformation were studied in the density functional theory frame. The mechanistic differences between the transformation of (Z,E)-germacranes and (E,E)-germacranes were also studied. We found that (Z,E)-germacranolides are significantly more stable than (E,E)-germacranolides and elemanolides. In the specific case of schkuhriolide, even when the boat transition state is not energetically favored, a previous hemiacetalization lowers enough the energetic barrier to allow the formation of a very stable elemanolide that is even more stable than its (Z,E)-germacrane.

[Satisfaction and perceived quality of people insured by the Social Health Protection in Mexico. Methodological foundations]. / Satisfacción y calidad percibida de afiliados al Sistema de Protección Social en Salud de México. Fundamentos metodológicos.

OBJECTIVE:: To describe the conceptual framework and methods for implementation and analysis of the satisfaction survey of the Mexican System for Social Protection in Health. MATERIALS AND METHODS:: We analyze the methodological elements of the 2013, 2014 and 2015 surveys, including the instrument, sampling method and study design, conceptual framework, and characteristics and indicators of the analysis. RESULTS:: The survey captures information on perceived quality and satisfaction. Sampling has national and State representation. Simple and composite indicators (index of satisfaction and rate of reported quality problems) are built and described. The analysis is completed using Pareto diagrams, correlation between indicators and association with satisfaction by means of multivariate models. CONCLUSIONS:: The measurement of satisfaction and perceived quality is a complex but necessary process to comply with regulations and to identify strategies for improvement. The described survey presents a design and rigorous analysis focused on its utility for improving.

Biogenesis of Triterpene Dimers from Orthoquinones Related to Quinonemethides: Theoretical Study on the Reaction Mechanism.

The biogenetic origin of triterpene dimers from the Celastraceae family has been proposed as assisted hetero-Diels-Alder reaction (HDA). In this work, computational calculation of HDA between natural quinonemethides (tingenone and isopristimerol) and hypothetical orthoquinones has been performed at the M06-2X/6-31G(d) level of theory. We have located all the HDA transition states supporting the biogenetic route via HDA cycloadditions. We found that all reactions take place through a concerted inverse electron demand and asynchronous mechanism. The enzymatic assistance for dimer formation was analyzed in terms of the calculated transition state energy barrier.

Assessment of hydrophobic interactions and their contributions through the analysis of the methane dimer.

Hydrophobic Interactions (HIs) are important in many phenomena of molecular recognition in chemistry and biology. Still, the relevance of HIs is sometimes difficult to evaluate particularly in large systems and intramolecular interactions. We put forward a method to estimate the magnitude and the different contributions of a given HI of the C···C, H-C···H, and H···H type through (i) the analysis of the electron density in the intermolecular region for eleven relative orientations of the methane dimer and (ii) the subsequent decomposition of the corresponding interaction energy in physically significant contributions using Symmetry Adapted Perturbation Theory (SAPT). Strong correlations were found between the topological properties of ρ(r) calculated at intermolecular bond critical points and Eint(SAPT) plus its different contributions with the C···C distance of the considered orientations of (CH4 )2 . These correlations were used to construct Mollier-like diagrams of Eint(SAPT) and its components as a function of the separation between two carbons and the orientation of the groups bonded to these atoms. The ethane dimer and tert-butylcyclohexane are used as representative examples of this new approach. Overall, we anticipate that this new method might prove useful in the study of both intramolecular and intermolecular HIs particularly of those within large systems wherein SAPT or electronic structure calculations are computationally expensive or even prohibitive.

The role of induced current density in Steroelectronic effects: Perlin effect.

The normal and reverse Perlin effect is usually explained by the redistribution of electron density produced by hyperconjugative mechanisms, which increases the electron population within axial or equatorial proton in normal or reverse effect, respectively. Here an alternative explanation for the Perlin effect is presented on the basis of the topology of the induced current density, which directly determines the nuclear magnetic shielding. Current densities around the C-H bond critical point and intra-atomic and interatomic contributions to the magnetic shielding explain the observed Perlin effect. The balance between intra-atomic and interatomic contributions determines the difference in the total atomic shielding. Normal Perlin effect is dominated by intra-atomic part, whereas reverse effect is dominated by interatomic contribution.

The rotational barrier of ethane and some of its hexasubstituted derivatives in terms of the forces acting on the electron distribution.

A novel and alternative explanation of the rotational barrier of ethane and several hexasubstituted derivatives, CX3CX3 (X = H, F, CH3, Cl, Br), is suggested based on the evaluation of the properties of the electron distribution. The forces exerted on the electron density of the topological atoms making up a molecule, the Ehrenfest forces, are analyzed and, with the help of the virial theorem, they are used to explain the experimental rotational barriers. According to this approach, the barrier is mainly a consequence of the decrease of the always attractive Ehrenfest forces (EFs) linking the two C atoms. In addition, the behavior of the EFs is related to a decrease of stability of the central C atoms, which is not compensated by the stabilization of the substituents. Also, during rotation from the staggered to the equilibrium conformation, the electron density at the C-C bond critical point and the electron delocalization between C atoms decrease and are accompanied by an increase of electron delocalization between the substituents. According to the analysis of the EF field lines and to the behavior of the integrated forces, the rotational barrier cannot be explained as a result of any repulsive forces acting on the electron density, although a possible interpretation of the quantum force that balances the EF in stationary states as a measure of traditional Pauli repulsions is also examined.

ent-Kaurene Glycosides from Ageratina cylindrica.

The aqueous extract of the leaves of Ageratina cylindrica afforded six new ent-kaurenoic acid glycosides together with the known diterpenoid paniculoside V, the flavonoid astragalin, chlorogenic acid, and L-chiro-inositol. The structures were elucidated mainly by NMR and MS methods, and the absolute configuration was established by vibrational circular dichroism spectroscopy. The new compounds showed moderate antiprotozoal activity against Entamoeba histolytica and Giardia lamblia trophozoites.

Vibrational circular dichroism (VCD), VCD exciton coupling, and X-ray determination of the absolute configuration of an α,ß-unsaturated germacranolide.

The absolute configuration of was deduced by vibrational circular dichroism together with the evaluation of the Flack and Hooft X-ray parameters. Vibrational circular dichroism exciton coupling, using the carbonyl group signals, confirmed the absolute configuration of . In addition, sodium borohydride reduction of the 11,13-double bond of 6-epi-desacetyllaurenobiolide () yields an almost equimolecular mixture of C11 epimers, while reduction of the same double bond of 6-epi-laurenobiolide () provided almost exclusively the (11S) diastereoisomer .

Properties of atoms in electronically excited molecules within the formalism of TDDFT.

The topological analysis of the electron density for electronic excited states under the formalism of the quantum theory of atoms in molecules using time-dependent density functional theory (TDDFT) is presented. Relaxed electron densities for electronic excited states are computed by solving a Z-vector equation which is obtained by means of the Sternheimer interchange method. This is in contrast to previous work in which the electron density for excited states is obtained using DFT instead of TDDFT, that is, through the imposition of molecular occupancies in accordance with the electron configuration of the excited state under consideration. Once the electron density of the excited state is computed, its topological characterization and the properties of the atoms in molecules are obtained in the same manner that for the ground state. The analysis of the low-lying π→π* singlet and triplet vertical excitations of CO and C6H6 are used as representative examples of the application of this methodology. Altogether, it is shown how this procedure provides insights on the changes of the electron density following photoexcitation and it is our hope that it will be useful in the study of different photophysical and photochemical processes.

Dynamic molecular graphs: "hopping" structures.

This work aims to contribute to the discussion about the suitability of bond paths and bond-critical points as indicators of chemical bonding defined within the theoretical framework of the quantum theory of atoms in molecules. For this purpose, we consider the temporal evolution of the molecular structure of [Fe{C(CH2 )3 }(CO)3 ] throughout Born-Oppenheimer molecular dynamics (BOMD), which illustrates the changing behaviour of the molecular graph (MG) of an electronic system. Several MGs with significant lifespans are observed across the BOMD simulations. The bond paths between the trimethylenemethane and the metallic core are uninterruptedly formed and broken. This situation is reminiscent of a "hopping" ligand over the iron atom. The molecular graph wherein the bonding between trimethylenemethane and the iron atom takes place only by means of the tertiary carbon atom has the longest lifespan of all the considered structures, which is consistent with the MG found by X-ray diffraction experiments and quantum chemical calculations. In contrast, the η(4) complex predicted by molecular-orbital theory has an extremely brief lifetime. The lifespan of different molecular structures is related to bond descriptors on the basis of the topology of the electron density such as the ellipticities at the FeCH2 bond-critical points and electron delocalisation indices. This work also proposes the concept of a dynamic molecular graph composed of the different structures found throughout the BOMD trajectories in analogy to a resonance hybrid of Lewis structures. It is our hope that the notion of dynamic molecular graphs will prove useful in the discussion of electronic systems, in particular for those in which analysis on the basis of static structures leads to controversial conclusions.

Structure, absolute configuration, and antidiarrheal activity of a thymol derivative from Ageratina cylindrica.

The leaves of Ageratina cylindrica afforded a thymol derivative that was characterized by physical and spectroscopical methods as (8S)-8,9-epoxy-6-hydroxy-l0-benzoyloxy-7-oxothymol isobutyrate (1). The absolute configuration of 1 was established as 8S by vibrational circular dichroism spectroscopy in combination with density functional theory calculations and by evaluation of the Flack and Hooft X-ray parameters. Compound 1 showed weak antiprotozoal activity against Entamoeba histolytica and Giardia lamblia trophozoites and a high inhibitory effect on hyperpropulsive movement of the small intestine in rats.

NMR-based conformational analysis of perezone and analogues.

Complete assignment of the (1)H NMR chemical shift and coupling constant values of perezone (1), O-methylperezone (2) and 6-hydroxyperezone (3) was carried out by total-line-shape-fitting calculations using the PERCH iterative spectra analysis software (PERCH Solutions Ltd., Kuopio, Finland). The resulting simulated spectra for the three compounds showed strong similarity to their corresponding experimental spectra. Particularly, all vicinal, allylic and homoallylic coupling constant values for the side chain of the three compounds were very similar, thus revealing that the conformation of these three molecules in solution is indeed almost identical. This fact is in agreement with extended side chain conformations over folded chain conformations because 1, 2 and 3 undergo completely different intramolecular cycloaddition reactions. In addition, results of double pulsed field gradient spin echo NOESY 1D experiments performed on perezone (1) were unable to provide evidence for folded conformers.

Modifications in the piperazine ring of nucleozin affect anti-influenza activity.

The infection caused by the influenza virus is a latent tret. The limited access to vaccines and approved drugs highlights the need for additional antiviral agents. Nucleozin and its analogs have gain attention for their promising anti-influenza activity. To contribute to the advancement of the discovery and design of nucleozin analogs, we analyzed piperazine-modified nucleozin analogs to increase conformational freedom. Also, we describe a new synthetic strategy to obtain nucleozin and its analogues, three molecules were synthesized and two of them were biologically evaluated in vitro. Although the analogues were less active than nucleozin, the loss of activity highlights the need for the piperazine ring to maintain the activity of nucleozin analogs. Interestingly, this result agrees with the prediction of anti-influenza activity made with a QSAR model presented in this work. The proposed model and the synthetic route will be useful for the further development of nucleozin analogs with antiviral activity.

H-Type Tracheoesophageal Fistula Cannulation for Rapid Intraoperative Localization.

Various techniques for tracheoesophageal fistula cannulation have been reported. In this case, we created a loop using a plastic catheter. The loop allowed us to create traction for rapid intraoperative localization and to pull a difficult-to-reach fistula, superiorly into the neck, to be reached through a cervical approach. Laryngoscope, 133:2425-2427, 2023.