Non-covalent interactions in the diastereoselective synthesis of cis-2,3-dihydrobenzofurans: experimental and computational studies.

The diastereoselective synthesis of 2,3-DHBs has been previously reported via an intramolecular Michael addition reaction using alkali bases such as Cs2CO3 and K2CO3. However, no systematic study has been performed to understand the possible role of bases in the mechanism of the reaction and factors behind the stereoselective outcome of the reaction. Herein, from experimental and theoretical points of view, we disclose the role of the cesium salt in the rate-determining step along the catalytic cycle and the key role of stabilizing non-covalent interactions in the stereoselective outcome of the reaction.

Mechanistic Insights into the DABCO-Catalyzed Cloke-Wilson Rearrangement: A DFT Perspective.

The mechanism and selectivity patterns of the DABCO-catalyzed Cloke-Wilson rearrangement were computationally studied in detail using density functional theory calculations. Our computations suggest that the process occurs stepwise involving the initial ring opening of the cyclopropane promoted by a DABCO molecule followed by a ring-closure reaction of the readily formed zwitterionic intermediate. The regioselectivity of the initial nucleophilic ring-opening step strongly depends on the nature of the substituent attached to the cyclopropane moiety. The physical factors governing the preference for the more sterically hindered C2 (tertiary) position have been quantitatively analyzed by applying the combined activation strain model-energy decomposition analysis method. In addition, our calculations revealed a new mechanism for the analogous transformation involving vinylcyclopropanes consisting of an initial SN2' ring-opening process followed by a 5-exo-trig cyclization step, which proceeds without facial selectivity.

A soil database from Queretaro, Mexico for assessment of crop and irrigation water requirements.

Several studies have assessed crop water requirements based on soil properties, but these have been on a small scale or on soils with similar textures. Here, a data base of soil measurements in the field and laboratory from sites across Irrigation District 023, San Juan del Rio, Queretaro, Mexico was sampled, collected, analyzed, and integrated. The data base, named, NaneSoil, contains information on 900 samples obtained from irrigated plots. NaneSoil cover 10 of the 12 textural classes with the following information: sand, silt, clay contents, bulk density, saturated volumetric water content, field capacity, permanent wilting point and saturated hydraulic conductivity. The aim of this work is to provide the scientific community with sufficient information to perform a large number of analyses, for example, development of pedotransfer functions, calculation of water requirements of plants in soils with similar characteristics, modeling of infiltration, optimal irrigation discharge calculation, among others. The dataset also promotes the scientific community to contribute their own measurements to further strengthen the knowledge of flow in the porous medium.

Selective Concurrence of the Long Non-Coding RNA MALAT1 and the Polycomb Repressive Complex 2 to Promoter Regions of Active Genes in MCF7 Breast Cancer Cells.

In cancer cells, the long non-coding RNA (lncRNA) MALAT1 has arisen as a key partner for the Polycomb Repressive Complex 2 (PRC2), an epigenetic modifier. However, it is unknown whether this partnership occurs genome-wide at the chromatin level, as most of the studies focus on single genes that are usually repressed. Due to the genomic binding properties of both macromolecules, we wondered whether there are binding sites shared by PRC2 and MALAT1. Using public genome-binding datasets for PRC2 and MALAT1 derived from independent ChIP- and CHART-seq experiments performed with the breast cancer cell line MCF7, we searched for regions containing PRC2 and MALAT1 overlapping peaks. Peak calls for each molecule were performed using MACS2 and then overlapping peaks were identified by bedtools intersect. Using this approach, we identified 1293 genomic sites where PRC2 and MALAT1 concur. Interestingly, 54.75% of those sites are within gene promoter regions (<3000 bases from the TSS). These analyses were also linked with the transcription profiles of MCF7 cells, obtained from public RNA-seq data. Hence, it is suggested that MALAT1 and PRC2 can concomitantly bind to promoters of actively-transcribed genes in MCF7 cells. Gene ontology analyses revealed an enrichment of genes related to categories including cancer malignancy and epigenetic regulation. Thus, by re-visiting occupancy and transcriptomic data, we identified a key gene subset controlled by the collaboration of MALAT1 and PRC2.

Selective reduction of nitroarenes using Ru/C and CaH2.

Herein, we report an efficient and highly selective method for the reduction of aromatic, heteroaromatic and halonitro compounds using the readily available and cost-effective Ru/C as a catalyst along with unconventional CaH2 as a source of hydride. In most cases the corresponding anilines can be obtained by simple filtration without further purification. The use of 2-MeTHF and the simple operational work-up constitute a valid alternative to previous methodologies.

Phenoxy- and Phenylamino-Heterocyclic Quinones: Synthesis and Preliminary Anti-Pancreatic Cancer Activity.

The successful application of fragment-based drug discovery strategy for the efficient synthesis of phenoxy- or phenylamino-2-phenyl-benzofuran, -benzoxazole and -benzothiazole quinones is described. Interestingly, in the final step of the synthesis of the target compounds, unusual results were observed on the regiochemistry of the reaction of bromoquinones with phenol and aniline. A theoretical study was carried out for better understanding the factors that control the regiochemistry of these reactions. The substituted heterocyclic quinones were evaluated in vitro to determine their cytotoxicity by the MTT method in three pancreatic cancer cell lines (MIA-PaCa-2, BxPC-3, and AsPC-1). Phenoxy benzothiazole quinone 26a showed potent cytotoxic activity against BxPC-3 cell lines, while phenylamino benzoxazole quinone 20 was the most potent on MIA-PaCa-2 cells. Finally, electrochemical properties of these quinones were determined to correlate with a potential mechanism of action. All these results, indicate that the phenoxy quinone fragment led to compounds with increased activity against pancreatic cancer cells.

Scissor Position of the Orthopedic Table for the Resolution of Intertrochanteric and Subtrochanteric Hip Fractures.

During the surgical resolution of intertrochanteric and subtrochanteric hip fractures on an orthopedic table, a fluoroscope needs to be used in orthogonal planes. This requires that the contralateral leg does not obstruct the radioscopic view, so patients are often placed in a hemilithotomy position. This position, also called the Lloyd-Davis position, involves hip flexion, hip abduction, hip external rotation, and knee flexion. However, rare complications, such as acute leg posterior compartment syndrome, have been described. In addition, patients with severe osteoarthritis and joint stiffness or a history of total hip arthroplasty may have difficulty achieving this position, and the well leg may be at risk of injury in a hemilithotomy position. A previously described position called the "scissor position" is, in our opinion, a safer and more efficient technique for placing the well leg on the orthopedic table, using only a pillow and a self-adhesive compression bandage. This simple position allows a lateral fluoroscopic view of the injured femur without overlapping or interference from the other limb.

Unraveling the Selectivity Patterns in Phosphine-Catalyzed Annulations of Azomethine Imines and Allenoates.

The mechanism and selectivity of phosphine-catalyzed [3 + 2] and [3 + 3] annulations of azomethine imines and allenoates have been computationally studied. Exploration of the potential energy surface reveals that the cyclization step is a key step controlling the selectivity of the process. This contrasts with previous studies on related transformations where the initial nucleophilic addition involving the activated allenoate was found to exclusively control the regioselectivity of the transformation. Among the possible reaction pathways, the energetically low-lying reaction channel involves an intramolecular Michael addition leading to the experimentally observed [3 + 2] product. The factors controlling the observed regioselectivity have been quantitatively rationalized by means of state-of-the-art computational methods, namely, the activation strain model of reactivity in combination with the energy decomposition analysis.

Reduction Over Condensation of Carbonyl Compounds Through a Transient Hemiaminal Intermediate Using Hydrazine.

Reduction of carbonyl moieties to the corresponding alcohol using simply hydrazine hydrate has been considerably unfeasible until now due to the well-known condensation reaction. However, herein, we report that using an excess of 20-fold equivalents, the reduction proceeds in excellent yields. 1H NMR study of the reaction and density functional theory (DFT) calculations indicate that the final fate of the hemiaminal intermediate is crucial to obtain the alcohol or the hydrazone.

Meisenheimer complexes as hidden intermediates in the aza-SNAr mechanism.

In this work we report a computational study about the aza-SNAr mechanism in fluorine- and chlorine-containing azines with the aim to unravel the physical factors that determine the reactivity patterns in these heterocycles towards propylamine. The nature of the reaction intermediate was analyzed in terms of its electronic structure based on a topological analysis framework in some non-stationary points along the reaction coordinate. The mechanistic dichotomy of a concerted or a stepwise pathway is interpreted in terms of the qualitative Diabatic Model of Intermediate Stabilization (DMIS) approach, providing a general mechanistic picture for the SNAr process involving both activated benzenes and nitrogen-containing heterocycles. With the information collected, a unified vision of the Meisenheimer complexes as transition state, hidden intermediate or real intermediate was proposed.

Influence of Non-Covalent Interactions in the Exo- and Regioselectivity of Aza-Diels-Alder Reactions: Experimental and DFT Calculations.

A systematic experimental and theoretical study of the intermolecular Aza-Diels-Alder reaction using 5-aminopyrrole as a building block shows that the commonly accepted endo selectivity, ruled by controversial secondary orbital interactions, are overcome by non-covalent interactions affording to the unusual exo adduct. Additionally, the regioselectivity is also influenced for such interactions. The starting materials are easily prepared, and the use of water as the solvent is a great achievement for the development of cleaner synthetic methodologies.

Burkholderia xenovorans LB400 possesses a functional polyhydroxyalkanoate anabolic pathway encoded by the pha genes and synthesizes poly(3-hydroxybutyrate) under nitrogen-limiting conditions.

Polyhydroxyalkanoates (PHAs) are biodegradable bioplastics that are synthesized by diverse bacteria. In this study, the synthesis of PHAs by the model aromatic-degrading strain Burkholderia xenovorans LB400 was analyzed. Twelve pha genes including three copies of phaC and five copies of the phasin-coding phaP genes are distributed among the three LB400 replicons. The phaC1ABR gene cluster that encodes the enzymes of the PHA anabolic pathway is located at chromosome 1 of strain LB400. During the growth of strain LB400 on glucose under nitrogen limitation, the expression of the phaC1, phaA, phaP1, phaR, and phaZ genes was induced. Under nitrogen limitation, PHA accumulation in LB400 cells was observed by fluorescence microscopy after Nile Red staining. GC-MS analyses revealed that the PHA accumulated under nitrogen limitation was poly(3-hydroxybutyrate) (PHB). LB400 cells grown on glucose as the sole carbon source under nitrogen limitation accumulated 40 ± 0.96% PHB of the cell dry weight, whereas no PHA was observed in cells grown in control medium. The functionality of the phaC1 gene from strain LB400 was further studied using heterologous expression in a Pseudomonas putida KT40C1ZC2 mutant strain derived from P. putida KT2440 that is unable to synthesize PHAs. Interestingly, KT40C1ZC2[pVNC1] cells that express the phaC1 gene from strain LB400 were able to synthesize PHB (33.5% dry weight). This study indicates that B. xenovorans LB400 possesses a functional PHA synthetic pathway that is encoded by the pha genes and is capable of synthesizing PHB.

Effect of dentin roughness on the adhesive performance in non-carious cervical lesions: A double-blind randomized clinical trial.

OBJECTIVE: This double-blind randomized clinical trial evaluates the influence of dentin roughening (RO) on the clinical behavior of a new universal multi-mode adhesive (Tetric N-Bond Universal; Ivoclar-Vivadent) applied as self-etch and as etch-and-rinse in non-carious cervical lesions (NCCLs). METHODS: A total of 192 restorations were randomly placed in 48 patients according to the following groups: ER - Etch-and-rinse (no preparation); SE - self-etch (no preparation); ER+RO and; SE+RO. The resin composite Empress Direct (Ivoclar-Vivadent) was placed incrementally. The restorations were evaluated after one week (baseline), 6 and 18 months, using the FDI and USPHS criteria. Statistical analyses were performed using appropriate tests (α=0.05). RESULTS: Fifteen restorations were lost at 18 months (3 for SE, 2 for ER, 5 for SE+RO and 5 for ER+RO) (p >0.05 between groups). Post-operative sensitivity wasn't observed in any of the recall periods. Eighty-four restorations were considered to have minor discrepancies in marginal adaptation at the 18-month recall using the FDI criteria (24 for SE, 18 for ER, 22 for SE+RO and 20 for ER+RO; p >0.05 between groups). Nineteen restorations were considered to have minor discrepancies in marginal discoloration at the 18-month recall (10 for SE, 03 for ER, 05 for SE+RO and 01 for ER+RO; p >0.05 between groups). CONCLUSION: The dentin roughening before application of Tetric N-Bond Universal as self-etch and etch-and-rinse didn't affect the clinical behavior of composite restorations placed in NCCLs.

From Rare to Dominant: a Fine-Tuned Soil Bacterial Bloom during Petroleum Hydrocarbon Bioremediation.

Hydrocarbons are worldwide-distributed pollutants that disturb various ecosystems. The aim of this study was to characterize the short-lapse dynamics of soil microbial communities in response to hydrocarbon pollution and different bioremediation treatments. Replicate diesel-spiked soil microcosms were inoculated with either a defined bacterial consortium or a hydrocarbonoclastic bacterial enrichment and incubated for 12 weeks. The microbial community dynamics was followed weekly in microcosms using Illumina 16S rRNA gene sequencing. Both the bacterial consortium and enrichment enhanced hydrocarbon degradation in diesel-polluted soils. A pronounced and rapid bloom of a native gammaproteobacterium was observed in all diesel-polluted soils. A unique operational taxonomic unit (OTU) related to the Alkanindiges genus represented ∼ 0.1% of the sequences in the original community but surprisingly reached >60% after 6 weeks. Despite this Alkanindiges-related bloom, inoculated strains were maintained in the community and may explain the differences in hydrocarbon degradation. This study shows the detailed dynamics of a soil bacterial bloom in response to hydrocarbon pollution, resembling microbial blooms observed in marine environments. Rare community members presumably act as a reservoir of ecological functions in high-diversity environments, such as soils. This rare-to-dominant bacterial shift illustrates the potential role of a rare biosphere facing drastic environmental disturbances. Additionally, it supports the concept of "conditionally rare taxa," in which rareness is a temporary state conditioned by environmental constraints.

Assessing environmental drivers of microbial communities in estuarine soils of the Aconcagua River in Central Chile.

Aconcagua River basin (Central Chile) harbors diverse economic activities such as agriculture, mining and a crude oil refinery. The aim of this study was to assess environmental drivers of microbial communities in Aconcagua River estuarine soils, which may be influenced by anthropogenic activities taking place upstream and by natural processes such as tides and flood runoffs. Physicochemical parameters were measured in floodplain soils along the estuary. Bacteria, Actinobacteria, Alphaproteobacteria, Betaproteobacteria, Pseudomonas, Bacillus and Fungi were studied by DGGE fingerprinting of 16S rRNA gene and ribosomal ITS-1 amplified from community DNA. Correlations between environment and communities were assessed by distance-based redundancy analysis. Mainly hydrocarbons, pH and the composed variable copper/arsenic/calcium but in less extent nitrogen and organic matter/phosphorous/magnesium correlated with community structures at different taxonomic levels. Aromatic hydrocarbons degradation potential by bacterial community was studied. Polycyclic aromatic hydrocarbon ring-hydroxylating dioxygenases genes were detected only at upstream sites. Naphthalene dioxygenase ndo genes were heterogeneously distributed along estuary, and related to Pseudomonas, Delftia, Comamonas and Ralstonia. IncP-1 plasmids were mainly present at downstream sites, whereas IncP-7 and IncP-9 plasmids showed a heterogeneous distribution. This study strongly suggests that pH, copper, arsenic and hydrocarbons are main drivers of microbial communities in Aconcagua River estuarine soils.

Mechanistic insights into the ANRORC-like rearrangement between methylhydrazine and 1,2,4-oxadiazole derivatives.

We herein present the first in-depth theoretical study devoted to elucidate the mechanism of the reaction between 1,2,4-oxadiazole derivatives and methylhydrazine. For this purpose, the reaction between methylhydrazine and some polyfluoroaryl-1,2,4-oxadiazoles has been employed as a model reaction. The analysis of the potential energy surface (PES) indicates that the most favorable path involves an initial amine attack at the C(2') site of the aryl moiety to yield an aryl-hydrazine intermediate whose thermodynamic stability appears as the main determinant of the favored reaction path. Next, the cyclization step leading to a spiro intermediate through a favored 5-exo-trig process appears as the rate determining step. Additionally, this study highlights the relevance of the torsional strain effects on the favored ANRORC pathway. Finally, both the origins of the substituent effects on the regioselectivity patterns as well as the need of using a large excess of nucleophile to afford the favored ANRORC pathway are discussed.

Investigating a potential biological treatment to prevent pathological fractures caused by unicameral bone cysts in children under 8 years.

INTRODUCTION: There is no consensus on when and how to treat unicameral bone cysts (UBCs), partly because of a lack of knowledge of the aetiology. PURPOSE: To review the different treatment techniques for UBCs and to describe our results with a single injection of autogenous bone marrow (BM) mixed with demineralised bone matrix (DBM) in very young children. PATIENTS AND METHODS: We reviewed five patients under the age of 8 years with UBCs treated by percutaneous aspiration and a single injection of BM associated with DBM. The cyst was located in the proximal humerus in four patients and in the proximal femur in one patient. Assessment of the need for surgery was based on the clinical and radiographic suspicion of new pathological fractures. The administration of a second injection, when necessary, was based on the surgeon's judgement regarding the risk of fracture. The mean follow-up after first injection was 41 months. RESULTS: There were no complications related to the procedure, except a non-displaced fracture, which healed without problems. All patients were pain free and progressively resumed their activities without restriction until a new fracture occurred in two cases. According to Capanna's classification, only one case healed completely (grade 1), one lesion was classified as grade 2, and there were three recurrences at 11, 12 and 27 months after initial treatment (grade 3). The final outcome was treatment failure for three out of the five patients. Two patients were treated with a second injection and one patient is waiting for surgery. CONCLUSION: A single injection of aspirated autogenous BM mixed with DBM in very young children with active UBCs at risk of fracture is very simple, comfortable and safe. Nevertheless, the results seem to be unpredictable and are probably more dependent on the natural evolution of the cyst than on the treatment. Further comparative studies with larger sample numbers are needed.

Bioremediation of petroleum hydrocarbons: catabolic genes, microbial communities, and applications.

Bioremediation is an environmental sustainable and cost-effective technology for the cleanup of hydrocarbon-polluted soils and coasts. In spite of that longer times are usually required compared with physicochemical strategies, complete degradation of the pollutant can be achieved, and no further confinement of polluted matrix is needed. Microbial aerobic degradation is achieved by the incorporation of molecular oxygen into the inert hydrocarbon molecule and funneling intermediates into central catabolic pathways. Several families of alkane monooxygenases and ring hydroxylating dioxygenases are distributed mainly among Proteobacteria, Actinobacteria, Firmicutes and Fungi strains. Catabolic routes, regulatory networks, and tolerance/resistance mechanisms have been characterized in model hydrocarbon-degrading bacteria to understand and optimize their metabolic capabilities, providing the basis to enhance microbial fitness in order to improve hydrocarbon removal. However, microbial communities taken as a whole play a key role in hydrocarbon pollution events. Microbial community dynamics during biodegradation is crucial for understanding how they respond and adapt to pollution and remediation. Several strategies have been applied worldwide for the recovery of sites contaminated with persistent organic pollutants, such as polycyclic aromatic hydrocarbons and petroleum derivatives. Common strategies include controlling environmental variables (e.g., oxygen availability, hydrocarbon solubility, nutrient balance) and managing hydrocarbon-degrading microorganisms, in order to overcome the rate-limiting factors that slow down hydrocarbon biodegradation.