Revealing the Critical Role of Global Electron Density Transfer in the Reaction Rate of Polar Organic Reactions within Molecular Electron Density Theory.

The critical role of global electron density transfer (GEDT) in increasing the reaction rate of polar organic reactions has been studied within the framework of Molecular Electron Density Theory (MEDT). To this end, the series of the polar Diels-Alder (P-DA) reactions of cyclopentadiene with cyanoethylene derivatives, for which experimental kinetic data are available, have been chosen. A complete linear correlation between the computed activation Gibbs free energies and the GEDT taking place at the polar transition state structures (TSs) is found; the higher the GEDT at the TS, the lower the activation Gibbs free energy. An interacting quantum atoms energy partitioning analysis allows for establishing a complete linear correlation between the electronic stabilization of the electrophilic ethylene frameworks and the GEDT taking place at the polar TSs. This finding supports Parr's proposal for the definition of the electrophilicity ω index. The present MEDT study establishes the critical role of the GEDT in the acceleration of polar reactions, since the electronic stabilization of the electrophilic framework with the electron density gain is greater than the destabilization of the nucleophilic one, making a net favorable electronic contribution to the decrease in the activation energy.

Post-COVID-19 condition in pregnant and postpartum women: a long-term follow-up, observational prospective study.

Background: Post-COVID-19 condition has recently been defined as new or persistent common COVID-19 symptoms occurring three months after disease onset. The pathology of the disease is unclear, but immune and vascular factors seem to play a significant role. The incidence, severity, and implications of the disease after COVID-19 infection in pregnancy have not been established. We aimed to study the incidence and main risk factors for post-COVID-19 condition in an obstetric population and their implications for maternal and perinatal morbimortality. Methods: This is a prospective observational cohort study undertaken including women during pregnancy or at admission for labour with acute COVID-19 infection from March 9th, 2020 to June 11th, 2022. The inclusion criteria were confirmed acute COVID-19 infection during the recruitment period, a lack of significant language barrier and consent for follow-up. Patients were clinically followed-up by telephone via semi structured questionnaires. The exclusion criteria were loss to follow-up, spontaneous miscarriage, and legal termination of pregnancy. Patients were classified into groups according to the severity of symptoms at onset. We included patients from the first six first waves of the pandemic according to national epidemiological data in Spain. We studied the incidence of post-COVID-19 condition and their main demographic, clinical and obstetric risk factors. Findings: A total of 409 pregnant women were recruited at acute diagnosis, and 286 were followed-up. The mean time to follow-up was 92 weeks (standard deviation ± 28 weeks; median 100 weeks (Interquartile range: 76; 112)). A total of 140 patients had at least one post-COVID-19 symptom at least three months after acute infection. Neurological (60%) and cutaneous (55%) manifestations were the most frequent findings. The following profiles were identified as presenting a higher risk of post-COVID-19 condition: migrant women born in countries with lower Human Development Index; multiparous women; women with COVID-19 during pregnancy, mainly during the first and third trimesters, and in the first and second waves of the pandemic; women who had a higher number of symptoms; women who had a higher incidence of moderate and severe symptoms; women who required hospitalisation due to COVID-19 complications; and women who were not vaccinated before disease onset. We did not find any significant difference in perinatal results, such as gestational week at delivery, birthweight, the need for neonatal care or 5-min Apgar score, and newborns benefited from a high rate of breastfeeding at discharge. Women who were infected during successive waves of the pandemic had a significant and constant decrease in the risk of post-COVID-19 condition comparing to estimated risk in the first wave (OR: 0.70; 95% CI: 0.62, 0.92). Symptoms tended to resolve over time heterogeneously. Symptoms of myalgia and arthralgia took longer to resolve (mean of 60 weeks and 54 weeks, respectively). In a small but significant proportion of patients, neurological and psycho-emotional symptoms tended to become chronic after 90 weeks. Interpretation: At least 34.2% of obstetric patients from our cohort with acute COVID-19 infection presented post-COVID-19 condition symptoms. Demographic and acute disease characteristics as well as specific pregnancy-related risk factors were identified. This is the first study to assess post-COVID-19 condition in pregnant women. Further analysis on the biological pathophysiology of post-COVID-19 is needed to explain the characteristics of the disease. Funding: This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "PI21/01244" and co-funded by the European Union, as well as P2022/BMD-7321 (Comunidad de Madrid) and ProACapital, Halekulani S.L. and MJR.

Synthesis and Characterization of New Spirooxindoles Including Triazole and Benzimidazole Pharmacophores via [3+2] Cycloaddition Reaction: An MEDT Study of the Mechanism and Selectivity.

A new series of spirooxindoles based on benzimidazole, triazole, and isatin moieties were synthesized via a [3+2] cycloaddition reaction protocol in one step. The single X-ray crystal structure of the intermediate triazole-benzimidazole 4 was solved. The new chemical structures of these spirooxindole molecules have been achieved for the first time. The final synthesized chemical architecture has differently characterized electronic effects. An MEDT study of the key 32CA reaction between in situ generated azomethine ylide (AY) and chalcones explained the low reaction rates and the total selectivities observed. The supernucleophilic character of AY and the strong electrophilicity of chalcones favor these reactions through a highly polar two-stage one-step mechanism in which bond formation at the ß-conjugated carbon of the chalcones is more advanced. The present combined experimental and theoretical study reports the synthesis of new spirooxindoles with potential biological activities and fully characterizes the molecular mechanisms for their formation through the key 32CA reaction step.

A Molecular Electron Density Theory Study of the Domino Reaction of N-Phenyl Iminoboranes with Benzaldehyde Yielding Fused Bicyclic Compounds.

The reaction of N-phenyl iminoborane with benzaldehyde yielding a fused aromatic compound, recently reported by Liu et al., has been studied within the Molecular Electron Density Theory (MEDT). Formation of the fused aromatic compound is a domino process that comprises three consecutive reactions: (i) formation of a weak molecular complex between the reagents; (ii) an intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent of iminoborane; and (iii) a formal 1,3-hydrogen shift yielding the final fused aromatic compound. The two last steps correspond to a Friedel-Crafts acylation reaction, the product of the second reaction being the tetrahedral intermediate of an electrophilic aromatic substitution reaction. However, the presence of the imino group adjacent to the aromatic ring strongly stabilizes the corresponding intermediate, being the reaction product when the ortho positions are occupied by t-butyl substituents. This domino reaction shows a great similitude with the Brønsted acid catalyzed Povarov reaction. Although N-phenyl iminoborane can experience a formal [2+2] cycloaddition reaction with benzaldehyde, its higher activation Gibbs free energy compared to the intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent, 6.6 kcal·mol-1, prevents the formation of the formal [2+2] cycloadduct. The present MEDT study provides a different vision of the molecular mechanism of these reactions based on the electron density.

A novel alpha-amylase inhibitor-based spirooxindole-pyrrolidine-clubbed thiochromene-pyrzaole pharmacophores: Unveiling the [3+2] cycloaddition reaction by molecular electron density theory.

A novel spirooxindole-pyrrolidine clubbed thiochromene and pyrazole motifs were synthesized by [3+2] cycloaddition (32CA) reactions in one step process starting from the ethylene-based thiochromene and pyrazole scaffolds with the secondary amino-acids and substituted isatins in high yield. The 32CA reaction of AY 10 with ethylene derivative 6 has also been studied with Molecular Electron Density Theory. The high nucleophilic character of AY 10, N = 4.39 eV, allows explaining that the most favorable TS-on is 13.9 kcal mol-1 below the separated reagent. This 32CA, which takes place through a non-concerted one-step mechanism, presents a total ortho regio- and endo stereoselectivity, which is controlled by the formation of two intramolecular H… O hydrogen bonds. The design of spirooxindole-pyrrolidines engrafted thiochromene and pyrazole was tested for alpha-amylase inhibition and show a high efficacy in nanoscale range of reactivity. The key interaction between the most active hybrids and the receptor was studied by molecular docking. The physiochemical properties of the designed spirooxindole-pyrrolidines were carried out by in silico ADMET prediction. The newly synthesized most potent hybrid could be considered as a lead compound for drug discovery development for type 2 diabetes mellitus (T2DM).

A combined BET and IQA-REG study of the activation energy of non-polar zw-type [3+2] cycloaddition reactions.

A combined Bonding Evolution Theory (BET) and Interacting Quantum Atoms-Relative Energy Gradient (IQA-REG) study is carried out on a non-polar zw-type [3+2] cycloaddition (32CA) reaction. BET is the joint use of Catastrophe Theory and the topology of the Electron Localization Function (ELF) to characterise molecular mechanisms, while IQA is a quantum topological energy partitioning method and REG is a method to compute chemical insight at atomistic level, usually in connection with energy. This 32CA reaction involves the simplest nitrone with ethylene and has been studied here at B3LYP/6-311G(d,p) level within the context of Molecular Electron Density Theory (MEDT), which is based on the idea that changes in electron density, and not molecular orbital interactions, are responsible for chemical reactivity. We aim to determine the origin of the high activation energy of 32CA reactions involving zwitterionic three-atom-components. The BET study and IQA-REG method are applied to the overall activation energy path. While BET suggests that the barrier is mainly associated with the rupture of the nitrone CN double bond, IQA-REG indicates that it is mainly related to the rupture of the ethylene CC double bond. The present study shows that activation energies can be accurately and easily described by IQA-REG, and its complementary use with BET helps achieving a more detailed description of molecular mechanisms.

The role of the T-cell mediated immune response to Cytomegalovirus infection in intrauterine transmission.

INTRODUCTION: Prognostic markers for fetal transmission of Cytomegalovirus (CMV) infection during pregnancy are poorly understood. Maternal CMV-specific T-cell responses may help prevent fetal transmission and thus, we set out to assess whether this may be the case in pregnant women who develop a primary CMV infection. METHODS: A multicenter prospective study was carried out at 8 hospitals in Spain, from January 2017 to April 2020. Blood samples were collected from pregnant women at the time the primary CMV infection was diagnosed to assess the T-cell response. Quantitative analysis of interferon producing specific CMV-CD8+/CD4+ cells was performed by intracellular cytokine flow cytometry. RESULTS: In this study, 135 pregnant women with a suspected CMV infection were evaluated, 60 of whom had a primary CMV infection and samples available. Of these, 24 mothers transmitted the infection to the fetus and 36 did not. No association was found between the presence of specific CD4 or CD8 responses against CMV at the time maternal infection was diagnosed and the risk of fetal transmission. There was no transmission among women with an undetectable CMV viral load in blood at diagnosis. CONCLUSIONS: In this cohort of pregnant women with a primary CMV infection, no association was found between the presence of a CMV T-cell response at the time of maternal infection and the risk of intrauterine transmission. A detectable CMV viral load in the maternal blood at diagnosis of the primary maternal infection may represent a relevant biomarker associated with fetal transmission.

Unveiling the high reactivity of experimental pseudodiradical azomethine ylides within molecular electron density theory.

The [3+2] cycloaddition (32CA) reactions of N-methyl azomethine ylide (AY) with styrene, benzaldehyde and methyl 2-formyl-benzoate (MFB) were studied within molecular electron density theory (MEDT), at the ωB97X-D/6-311G(d) computational level, in order to characterize the reactivity of an experimental pseudodiradical TAC for the first time. ELF topological analysis indicates that AY presents a pseudodiradical structure. Analysis of CDFT reactivity indices allows classifying AY as a supernucleophile; while styrene is classified as a moderate electrophile, benzaldehyde and MFB are classified as strong electrophiles. The 32CA reaction with MFB is the most favorable one with a relatively low activation Gibbs free energy of 6.9 kcal mol-1, being irreversible and completely endo stereo- and chemo-selective towards the carbonyl group, a behavior predicted by the analysis of the Parr functions. The bonding evolution theory (BET) study indicates that while the 32CA reaction of AY with styrene is characterized as a pdr-type 32CA reaction, the one involving benzaldehyde follows a pmr-type mechanism prompted by the presence of the carbonyl group. The present MEDT study describes in detail the tunable high reactivity of one of the few experimentally available pseudodiradical TACs, showing that the mechanism of 32CA reactions can be modified not only by changing the electronic structure of TACs through proper substitution but also by the nature of their opposing ethylene derivative.

Unveiling the non-polar [3+2] cycloaddition reactions of cyclic nitrones with strained alkylidene cyclopropanes within a molecular electron density theory study.

The role of cyclopropane substitution on the ethylene in zw-type [3+2] cycloaddition (32CA) reactions of cyclic nitrones has been studied within Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) computational level. Electron Localization Function (ELF) analysis of the ethylenes shows that the presence the cyclopropane only slightly increases the electron density in the C-C bonding region. Analysis of the Conceptual DFT reactivity indices indicates that the presence of the cyclopropane does not produce any remarkable change in the reactivity of these strained ethylenes. The marginal electrophilic character of ethylene makes the zw-type 32CA reactions of non-polar character. The presence of the cyclopropane in the ethylene decreases the activation enthalpy of the 32CA reactions by only 1.7 and 2.6 kcal mol-1, and also decreases the ortho regioselectivity. The loss of the strain present in the cyclopropane is responsible for the reduction of the activation enthalpy and the increase of the reaction enthalpy in these non-polar 32CA reactions. The presence of the cyclopropane does not cause any change, neither in the transition state structure (TS) geometries nor in their electronic structure. The very low global electron density transfer (GEDT) computed at the TSs confirms the non-polar character of these 32CA reactions. The ortho regioselectivity experimentally observed in these non-polar 32CA reactions is determined by the most favorable two-center interaction between the less electronegative C1 carbon of nitrone and the non-substituted methylene C5 carbon of the ethylenes.

A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of an Azomethine Ylide with an Electrophilic Ethylene Linked to Triazole and Ferrocene Units.

The [3+2] cycloaddition (32CA) reaction of an azomethine ylide (AY) with an electrophilic ethylene linked to triazole and ferrocene units has been studied within the Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) level. The topology of the electron localization function (ELF) of this AY allows classifying it as a pseudo(mono)radical species characterized by the presence of two monosynaptic basins, integrating a total of 0.76 e, at the C1 carbon. While the ferrocene ethylene has a strong electrophilic character, the AY is a supernucleophile, suggesting that the corresponding 32CA reaction has a high polar character and a low activation energy. The most favorable ortho/endo reaction path presents an activation enthalpy of 8.7 kcal·mol-1, with the 32CA reaction being exergonic by -42.1 kcal·mol-1. This reaction presents a total endo stereoselectivity and a total ortho regioselectivity. Analysis of the global electron density transfer (GEDT) at the most favorable TS-on (0.23 e) accounts for the high polar character of this 32CA reaction, classified as forward electron density flux (FEDF). The formation of two intermolecular hydrogen bonds between the two interacting frameworks at the most favorable TS-on accounts for the unexpected ortho regioselectivity experimentally observed.

A Comprehensive Experimental and Theoretical Study on the [{(η5-C5H5)2Zr[P(µ-PNEt2)2P(NEt2)2P]}]2O Crystalline System.

The structure of tetraphosphetane zirconium complex C52H100N8OP10Zr21 was determined by single crystal X-ray diffraction analysis. The crystal belongs to the monoclinic system, space group P21/c, with a = 19.6452(14), b = 17.8701(12), c = 20.7963(14)Å, α = γ = 90°, ß = 112.953(7)°, V = 6722.7(8)Å3, Z = 4. The electronic structure of the organometallic complex has been characterized within the framework of Quantum Chemical Topology. The topology of the Electron Localization Function (ELF) and the electron density according to the Quantum Theory of Atoms in Molecules (QTAIM) show no covalent bonds involving the Zr atom, but rather dative, coordinate interactions between the metal and the ligands. This is the first reported case of a Zr complex stabilized by an oxide anion, anionic cyclopentadienyl ligands and rare tetraphosphetane anions.

The Participation of 3,3,3-Trichloro-1-nitroprop-1-ene in the [3 + 2] Cycloaddition Reaction with Selected Nitrile N-Oxides in the Light of the Experimental and MEDT Quantum Chemical Study.

The regioselective zw-type [3 + 2] cycloaddition (32CA) reactions of a series of aryl-substituted nitrile N-oxides (NOs) with trichloronitropropene (TNP) have been both experimentally and theoretically studied within the Molecular Electron Density Theory (MEDT). Zwitterionic NOs behave as moderate nucleophiles while TNP acts as a very strong electrophile in these polar 32CA reactions of forward electron density flux, which present moderate activation Gibbs free energies of 22.8-25.6 kcal·mol-1 and an exergonic character of 28.4 kcal·mol-1 that makes them irreversible and kinetically controlled. The most favorable reaction is that involving the most nucleophilic MeO-substituted NO. Despite Parr functions correctly predicting the experimental regioselectivity with the most favorable O-CCCl3 interaction, these reactions follow a two-stage one-step mechanism in which formation of the O-C(CCl3) bond takes place once the C-C(NO2) bond is already formed. The present MEDT concludes that the reactivity differences in the series of NOs come from their different nucleophilic activation and polar character of the reactions, rather than any mechanistic feature.

The catalytic effects of a thiazolium salt in the oxa-Diels-Alder reaction between benzaldehyde and Danishefsky's diene: a molecular electron density theory study.

The oxa-Diels-Alder (ODA) reaction of benzaldehyde with Danishefsky's diene in the presence of a [thiazolium][Cl] salt, as a model of an ionic liquid, has been studied within Molecular Electron Density Theory (MEDT) at the M06-2X/6-311G(d,p) computational level. The formation of two hydrogen bonds (HBs) between the thiazolium cation and the carbonyl oxygen of benzaldehyde modifies neither the electrophilic character of benzaldehyde nor its electronic structure substantially but accelerates the reaction considerably. This ODA reaction presents an activation energy of 4.5 kcal mol-1; the formation of the only observed dihydropyranone is strongly exothermic by -28.8 kcal mol-1. The presence of the [thiazolium][Cl] salt decreases the Gibbs free energy of activation of the ODA reaction between benzaldehyde and Danishefsky's diene by 5.9 kcal mol-1. This ODA reaction presents total para regioselectivity and high endo stereoselectivity. This ODA reaction takes place through a highly asynchronous polar transition state structure (TS) associated with a non-concerted two-stage one-step mechanism. ELF analysis of para/endo TSs associated with the ODA reactions in the absence and presence of the [thiazolium][Cl] salt shows that the formation of the HBs at the TSs does not modify their electronic structure substantially. This MEDT study makes it possible to conclude that the acceleration found in the ODA reaction of benzaldehyde with Danishefsky's diene in ILs is a consequence of an increase of the global electron density transfer at TS3-pn, resulting from HB formation, and the greater strength of the HBs at the polar TS3-pn compared to that at the benzaldehyde : [thiazolium][Cl] complex, and that the strength in the HB formed is more relevant that than an increase of the electrophilic character of the interaction between reagent.

Effects of Non-thermal Ultrasound on a Fibroblast Monolayer Culture: Influence of Pulse Number and Pulse Repetition Frequency.

Despite the use of therapeutic ultrasound in the treatment of soft tissue pathologies, there remains some controversy regarding its efficacy. In order to develop new treatment protocols, it is a common practice to carry out in vitro studies in cell cultures before conducting animal tests. The lack of reproducibility of the experimental results observed in the literature concerning in vitro experiments motivated us to establish a methodology for characterizing the acoustic field in culture plate wells. In this work, such acoustic fields are fully characterized in a real experimental configuration, with the transducer being placed in contact with the surface of a standard 12-well culture plate. To study the non-thermal effects of ultrasound on fibroblasts, two different treatment protocols are proposed: long pulse (200 cycles) signals, which give rise to a standing wave in the well with the presence of cavitation (ISPTP max = 19.25 W/cm2), and a short pulse (five cycles) of high acoustic pressure, which produces a number of echoes in the cavity (ISPTP = 33.1 W/cm2, with Pmax = 1.01 MPa). The influence of the acoustic intensity, the number of pulses, and the pulse repetition frequency was studied. We further analyzed the correlation of these acoustic parameters with cell viability, population, occupied surface, and cell morphology. Lytic effects when cavitation was present, as well as mechanotransduction reactions, were observed.

Understanding the Participation of Fluorinated Azomethine Ylides in Carbenoid-Type [3 + 2] Cycloaddition Reactions with Ynal Systems: A Molecular Electron Density Theory Study.

The carbenoid-type (cb-type) 32CA reaction of 1,1-difluoroated azomethine ylide (DFAY) with phenylpropynal has been studied using the molecular electron density theory (MEDT). Electron localization function (ELF) characterizes DFAY as a carbenoid species participating in cb-type 32CA reactions. The supernucleophilic character of DFAY and the strong electrophilic character of the ynal cause this polar 32CA reaction to have an unappreciable barrier; the reaction, which is highly exothermic, presents total chemo- and regioselectivity. ELF topological analysis of the bonding changes along the reaction establishes its non-concerted two-stage one-step mechanism, in which the nucleophilic attack of the carbenoid carbon of DFAY on the electrophilic carbonyl carbon of the ynal characterizes the cb-type reactivity of this three-atom component (TAC). The presence of two fluorines at DFAY modifies the pseudodiradical structure and reactivity of the simplest azomethine ylide to that of a carbenoid TAC participating in cb-type 32CA reactions toward electrophilic ethylenes.

Unveiling the Ionic Diels-Alder Reactions within the Molecular Electron Density Theory.

The ionic Diels-Alder (I-DA) reactions of a series of six iminium cations with cyclopentadiene have been studied within the Molecular Electron Density Theory (MEDT). The superelectrophilic character of iminium cations, ω > 8.20 eV, accounts for the high reactivity of these species participating in I-DA reactions. The activation energies are found to be between 13 and 20 kcal·mol-1 lower in energy than those associated with the corresponding Diels-Alder (DA) reactions of neutral imines. These reactions are low endo selective as a consequence of the cationic character of the TSs, but highly regioselective. Solvents have poor effects on the relative energies, and an unappreciable effect on the geometries. In acetonitrile, the activation energies increase slightly as a consequence of the better solvation of the iminium cations than the cationic TSs. Electron localization function (ELF) topological analysis of the bonding changes along the I-DA reactions shows that they are very similar to those in polar DA reactions. The present MEDT study establishes that the global electron density transfer (GEDT) taking place at the TSs of I-DA reactions, and not steric (Pauli) repulsions such as have been recently proposed, are responsible for the features of these types of DA reactions.

A New Multiplatform Model for Outpatient Prenatal and Postpartum Care in a Cohort of COVID-19-Affected Obstetric Patients.

Spain was one of the epicenters of the first wave of the COVID-19 pandemic. We describe in this article the design and results of a new telephone-and-telematic multiplatform model of systematic prenatal and postpartum follow-up for COVID-19-affected women implemented in a tertiary reference hospital in Madrid. We included patients with RT-PCR-confirmed COVID-19 during pregnancy or delivery from 10 March 2020 to 15 December 2020. We had a total of 211 obstetric patients: 148 (70.1%) were tested at the onset of suspicious clinical manifestations and 62 (29.4%) were tested in the context of routine screening. Of all the patients, 60 women (28.4%) were asymptomatic and 97 (46%) presented mild symptoms. Fifty-one women (24.2%) were admitted to our hospital for specific treatment because of moderate or severe symptoms. We had no missed cases and a good adherence. The mean number of calls per patient was 2.3. We performed 55 in-person visits. We analyzed the complexity of our program over time, showing a two-wave-like pattern. One patient was identified as needing hospitalization and we did not record major morbidity. Telemedicine programs are a strong and reproducible tool to reach to pregnant population affected by COVID-19, to assess its symptoms and severity, and to record for pregnancy-related symptoms both in an outpatient regime and after discharge from hospital.

Understanding the different reactivity of (Z)- and (E)-ß-nitrostyrenes in [3+2] cycloaddition reactions. An MEDT study.

The experimental reactivity of isomeric (Z)- and (E)-ß-nitrostyrenes participating in [3+2] cycloaddition (32CA) reactions has been analysed on the basis of molecular electron density theory (MEDT) at the HF/6-311G(d,p), B3LYP/6-311G(d,p) and ωB97X-D/6-311G(d,p) computational levels. It was found that the polar zw-type 32CA reactions with 5,5-dimethylpyrroline-N-oxide proceed via a one-step mechanism, characterised by the attack of the nucleophilic oxygen centre of the nitrone on the electrophilically activated ß-position of these nitrostyrenes. This behaviour is completely understood by means of the analysis of the conceptual DFT reactivity indices. These 32CA reactions present low activation enthalpies of 4.4 (Z) and 5.0 (E) kcal mol-1, and are exo (Z) and endo (E) stereoselective (B3LYP), as well as completely meta regioselective (ωB97X-D, B3LYP). The less stable (Z)-ß-nitrostyrene is more reactive than the (E)-one (HF). ELF and AIM topological analyses of the reagents and TSs show the great similitude between their electronic structures. Finally, NCI allows explaining the exo stereoselectivity found in the reaction of (Z)-ß-nitrostyrene. The present MEDT study explains the different reactivity, selectivity and competitiveness in the title reactions.

Divulging the various chemical reactivity of trifluoromethyl-4-vinyl-benzene as well as methyl-4-vinyl-benzene in [3+2] cycloaddition reactions.

In the present paper, an investigation about the [3 + 2]cycloaddition (32 C A) reactions of benzonitrile oxide with 1-trifluoromethyl-4-vinyl-benzene, and with 1-methyl-4-vinyl-benzene, using the Molecular Electron Density Theory (MEDT) through DFT/B3LYP/6-311++G (d,p), is performed. A deep mechanistic study beside an accurate electronic description of different stationary points along the IRC paths of the two 32 C A reactions have performed by examining the two competitive regioisomericortho/metareaction pathways, and providing the mechanism associated with them. The presence of the CF3 group reduces the activation energy, which makes it possible to increase the experimental yield of the reaction in good agreement with the experimental results. Addition of solvent (THF) does not affected the regioselectivity of the studied reactions. Evaluation of the ELF of selected structures of the IRC related with the formation of C-O and C-C single bonds designates that these 32 C A reactions take place through a one-step, two-stage mechanism.

Development of Biocomposite Polymeric Systems Loaded with Antibacterial Nanoparticles for the Coating of Polypropylene Biomaterials.

The development of a biocomposite polymeric system for the antibacterial coating of polypropylene mesh materials for hernia repair is reported. Coatings were constituted by a film of chitosan containing randomly dispersed poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with chlorhexidine or rifampicin. The chlorhexidine-loaded system exhibited a burst release during the first day reaching the release of the loaded drug in three or four days, whereas rifampicin was gradually released for at least 11 days. Both antibacterial coated meshes were highly active against Staphylococcus aureus and Staphylococcus epidermidis (106 CFU/mL), displaying zones of inhibition that lasted for 7 days (chlorhexidine) or 14 days (rifampicin). Apparently, both systems inhibited bacterial growth in the surrounding environment, as well as avoided bacterial adhesion to the mesh surface. These polymeric coatings loaded with biodegradable nanoparticles containing antimicrobials effectively precluded bacterial colonization of the biomaterial. Both biocomposites showed adequate performance and thus could have potential application in the design of antimicrobial coatings for the prophylactic coating of polypropylene materials for hernia repair.