Highly Efficient Production of Heteroarene Phosphonates by Dichromatic Photoredox Catalysis

[EN] A new strategy to achieve efficient aerobic phosphorylation of five-membered heteraroenes with excellent yields using dichromatic photoredox catalysis in a gel-based nanoreactor is described here. The procedure involves visible aerobic irradiation (cold white LEDs) of a mixture containing the heteroarene halide, trisubstituted phospite, N,N-diisopropylethylamine (DIPEA) as sacrificial agent, and catalytic amounts of 9,10-dicyanoanthracene (DCA) in the presence of an adequate gelator, which permits a faster process than at the homogeneous phase. The methodology, which operates by a consecutive photoinduced electron transfer (ConPET) mechanism, has been successfully applied to the straightforward and clean synthesis of a number of different heteroarene (furan, thiophene, selenophene, pyrrole, oxazole, or thioxazole) phosphonates, extending to the late-stage phosphonylation of the anticoagulant rivaroxaban. Strategically, employment of cold white light is critical since it provides both selective wavelengths for exciting first DCA (blue region) and subsequently its corresponding radical anion DCA(center dot-) (green region). The resultant strongly reducing excited agent DCA(center dot-)* is capable of even activate five-membered heteroarene halides (Br, Cl) with high reduction potentials (similar to-2.7 V) to effect the C(sp(2))-P bond formation. Spectroscopic and thermodynamic studies have supported the proposed reaction mechanism. Interestingly, the rate of product formation has been clearly enhanced in gel media because reactants can be presumably localized not only in the solvent pools but also through to the fibers of the viscoelastic gel network. This has been confirmed by field-emission scanning electron microscopy images where a marked densification of the network has been observed, modifying its fibrillary morphology. Finally, rheological measurements have shown the resistance of the gel network to the incorporation of the reactants and the formation of the desired products.Financial support from the Generalitat Valenciana (CIDEGENT/2018/044) and the Spanish Ministry of Science and Innovation (PID2019-105391GB-C21, PID2019-105391GBC22, BES-2017-080215, and BEAGAL18/00166) is gratefully acknowledged. D.D.D. thanks NANOTech., INTech, Cabildo de Tenerife, and ULL for laboratory facilities. We also thank the Electron Microscopy Service from the UPV.Herrera-Luna, JC.; Díaz Díaz, D.; Jiménez Molero, MC.; Pérez-Ruiz, R. (2021). Highly Efficient Production of Heteroarene Phosphonates by Dichromatic Photoredox Catalysis. ACS Applied Materials & Interfaces. 13(41):48784-48794. https://doi.org/10.1021/acsami.1c14497S4878448794134

Antiprotozoal and antimycobacterial activities of Persea americana seeds

BACKGROUND: Persea americana seeds are widely used in traditional Mexican medicine to treat rheumatism, asthma, infectious processes as well as diarrhea and dysentery caused by intestinal parasites. METHODS: The chloroformic and ethanolic extracts of P. americana seeds were prepared by maceration and their amoebicidal, giardicidal and trichomonicidal activity was evaluated. These extracts were also tested against Mycobacterium tuberculosis H37Rv, four mono-resistant and two multidrug resistant strains of M. tuberculosis as well as five non tuberculosis mycobacterium strains by MABA assay. RESULTS: The chloroformic and ethanolic extracts of P. americana seeds showed significant activity against E. histolytica, G. lamblia and T. vaginalis (IC(50) <0.634 μg/ml). The chloroformic extract inhibited the growth of M. tuberculosis H37Rv, M. tuberculosis MDR SIN 4 isolate, three M. tuberculosis H37Rv mono-resistant reference strains and four non tuberculosis mycobacteria (M. fortuitum, M. avium, M. smegmatis and M. absessus) showing MIC values ≤50 μg/ml. Contrariwise, the ethanolic extract affected only the growth of two mono-resistant strains of M. tuberculosis H37Rv and M. smegmatis (MIC ≤50 μg/ml). CONCLUSIONS: The CHCl(3) and EtOH seed extracts from P. americana showed amoebicidal and giardicidal activity. Importantly, the CHCl(3) extract inhibited the growth of a MDR M. tuberculosis isolate and three out of four mono-resistant reference strains of M. tuberculosis H37Rv, showing a MIC = 50 μg/ml. This extract was also active against the NTM strains, M. fortuitum, M. avium, M. smegmatis and M. abscessus, with MIC values <50 μg/ml

Aerobic Visible-Light-Driven Borylation of Heteroarenes in a Gel Nanoreactor

[EN] Heteroarene boronate esters constitute valuable intermediates in modern organic synthesis. As building blocks, they can be further applied to the synthesis of new materials, since they can be easily transformed into any other functional group. Efforts toward novel and efficient strategies for their preparation are clearly desirable. Here, we have achieved the borylation of commercially available heteroarene halides under very mild conditions in an easy-to-use gel nanoreactor. Its use of visible light as the energy source at room temperature in photocatalyst-free and aerobic conditions makes this protocol very attractive. The gel network provides an adequate stabilizing microenvironment to support wide substrate scope, including furan, thiophene, selenophene, and pyrrole boronate esters.Financial support from the Generalitat Valenciana (CIDEGENT/2018/044) and the Spanish Ministry of Science and Innovation (PID2019-105391GB-C21, PID2019-105391GBC22, BEAGAL18/00166, and BES-2017-080215) is gratefully acknowledged. We thank the Electron Microscopy Service from the UPV and Prof. Julia Perez-Prieto for spectroscopy facilities. D.D.D. also thanks NANOtec, INTech, Cabildo de Tenerife, and ULL for laboratory facilities.Herrera-Luna, JC.; Díaz Díaz, D.; Abramov, A.; Encinas Perea, S.; Jiménez Molero, MC.; Pérez-Ruiz, R. (2021). Aerobic Visible-Light-Driven Borylation of Heteroarenes in a Gel Nanoreactor. Organic Letters. 23(6):2320-2325. https://doi.org/10.1021/acs.orglett.1c004512320232523

Effective Formation of New C(sp2)-S Bonds via Photoactivation of Alkylamine-based Electron Donor-Acceptor Complexes

[EN] A novel visible light promoted formation of CAryl-S bonds through electron donor-acceptor (EDA) complexes of alkylamines with 5- and 6-membered (hetero)arene halides is presented. This represents the first EDA-based thiolation method not relying on pi-pi or a thiolate-anion-pi interactions and provides a facile access to heteroarene radicals, which can be suitably trapped by disulfide derivatives to form the corresponding versatile arylsulfides. Mechanistic investigations on the aspects of the whole process were conducted by spectroscopic measurements, demonstrating the hypothesized EDA complex formation. Moreover, the strength of this method has been proven by a gram-scale synthesis of thiolated products and the late-stage derivatization of an anticoagulant drug.Financial support from the Generalitat Valenciana (project CIDEGENT/2018/044), the Spanish Government (project PID2019-105391GB-C22 and fellowship BES-2017-080215 funded by MCIN/AEI/10.13039/501100011033) is gratefully acknowledged. The Deutsche Forschungsgemeinschaft (DFG, project GA1594/6-2) and the European Research Council (ERC-CG 724695) are also acknowledged for generous support.Herrera-Luna, JC.; Pérez-Aguilar, MC.; Gerken, L.; Garcia Mancheño, O.; Jiménez Molero, MC.; Pérez-Ruiz, R. (2023). Effective Formation of New C(sp2)-S Bonds via Photoactivation of Alkylamine-based Electron Donor-Acceptor Complexes. Chemistry - A European Journal. 29(6). https://doi.org/10.1002/chem.20220335329

Carcinoma neuroendocrino de tiroides calcitonina negativa: Reporte de caso y revisión de la literatura

Medullary thyroid carcinoma (MTC) is a relatively rare neuroendocrine tumor that originates in the parafollicular C cells of the thyroid gland. It is characterized by the synthesis and secretion of calcitonin. Usually, serum calcitonin is used as part of the diagnosis and follow-up of these patients. Few cases of MTC with negative calcitonin have been reported worldwide, whose diagnosis is a clinical challenge.El carcinoma medular de tiroides (MTC) es un tumor neuroendocrino relativamente raro que se origina en las células C para foliculares de la glándula tiroides. Se caracteriza por la síntesis y secreción de calcitonina. Por lo general, la calcitonina sérica se utiliza como parte del diagnóstico y seguimiento de estos pacientes. Se han notificado pocos casos de MTC con calcitonina negativa en todo el mundo, cuyo diagnóstico es un desafío clínico

Recent applications of biphotonic processes in organic synthesis

Currently, evolution of chemical transformations by visible light irradiation is highly desirable from cost, safety, availability, and environmental friendliness points of view. Besides, activation of less reactive substrates under very mild conditions becomes one of the most challenging tasks in organic synthesis. However, the insufficient energy provided by one photon of visible light for their activation definitely makes necessary the development of new protocols together with the design of new photocatalytic systems to overcome this limitation. In this context, the implementation of biphotonic processes has been found to be a solution for these drawbacks. This new mechanistic paradigm which combines light upconversion processes with energy/electron transfers holds great potential for high energy demanding bond activations, expanding the accessible reactivity window. Here, we wish to highlight the recent applications of biphotonic processes in organic synthesis.Generalitat ValencianaGobierno de Españ

Comparison of Night, Day and 24 h Motor Activity Data for the Classification of Depressive Episodes

Major Depression Disease has been increasing in the last few years, affecting around 7 percent of the world population, but nowadays techniques to diagnose it are outdated and inefficient. Motor activity data in the last decade is presented as a better way to diagnose, treat and monitor patients suffering from this illness, this is achieved through the use of machine learning algorithms. Disturbances in the circadian rhythm of mental illness patients increase the effectiveness of the data mining process. In this paper, a comparison of motor activity data from the night, day and full day is carried out through a data mining process using the Random Forest classifier to identified depressive and non-depressive episodes. Data from Depressjon dataset is split into three different subsets and 24 features in time and frequency domain are extracted to select the best model to be used in the classification of depression episodes. The results showed that the best dataset and model to realize the classification of depressive episodes is the night motor activity data with 99.37% of sensitivity and 99.91% of specificity

Persistence of COVID-19 Symptoms after Recovery in Mexican Population

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease (COVID-19), a highly contagious infectious disease that has caused many deaths worldwide. Despite global efforts, it continues to cause great losses, and leaving multiple unknowns that we must resolve in order to face the pandemic more effectively. One of the questions that has arisen recently is what happens, after recovering from COVID-19. For this reason, the objective of this study is to identify the risk of presenting persistent symptoms in recovered from COVID-19. This case-control study was conducted in one state of Mexico. Initially the data were obtained from the participants, through a questionnaire about symptoms that they had at the moment of the interview. Initially were captured the collected data, to make a dataset. After the pre-processed using the R project tool to eliminate outliers or missing data. Obtained finally a total of 219 participants, 141 recovered and 78 controls. It was used confidence level of 90% and a margin of error of 7%. From results it was obtained that all symptoms have an associated risk in those recovered. The relative risk of the selected symptoms in the recovered patients goes from 3 to 22 times, being infinite for the case of dyspnea, due to the fact that there is no control that presents this symptom at the moment of the interview, followed by the nausea and the anosmia with a RR of 8.5. Therefore, public health strategies must be rethought, to treat or rehabilitate, avoiding chronic problems in patients recovered from COVID-19

Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status

Background: Early prognosis in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is unreliable, especially in patients undergoing mild hypothermia. We aimed at developing a reliable risk-score to enable early prediction of cerebral performance and survival. Methods: Sixty-one out of 239 consecutive patients undergoing mild hypothermia after cardiac arrest, with eventual return of spontaneous circulation (ROSC), and comatose status on admission fulfilled the inclusion criteria. Background clinical variables, VF time and frequency domain fundamental variables were considered. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (n = 32; September 2006 September 2011, 48.5 ± 10.5 months of follow-up) and further validated in a prospective cohort (n = 29; October 2011 July 2013, 5 ± 1.8 months of follow-up). Results: FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p &lt; 0.001). Retrospective multivariate analysis provided a prediction model (sensitivity = 0.94, specificity = 1) that included spectral dominant frequency, derived power density and peak ratios between high and low frequency bands, and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity = 0.88 and specificity = 0.91. A model-derived risk-score properly predicted 93% of FNP. Testing the model on follow-up showed a c-statistic &#8805; 0.89. Conclusions: A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors undergoing mild hypothermia after cardiac arrest.the CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation.Filgueiras-Rama, D.; Calvo Saiz, CJ.; Salvador-Montañés, Ó.; Cádenas, R.; Ruiz-Cantador, J.; Armada, E.; Rey, JR.... (2015). Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status. International Journal of Cardiology. 186:250-258. doi:10.1016/j.ijcard.2015.03.074S25025818