Beyond classical sulfone chemistry: metal- and photocatalytic approaches for C-S bond functionalization of sulfones

The exceptional versatility of sulfones has been extensively exploited in organic synthesis across several decades. Since the first demonstration in 2005 that sulfones can participate in Pd-catalysed Suzuki-Miyaura type reactions, tremendous advances in catalytic desulfitative functionalizations have opened a new area of research with burgeoning activity in recent years. This emerging field is displaying sulfone derivatives as a new class of substrates enabling catalytic C-C and C-X bond construction. In this review, we will discuss new facets of sulfone reactivity toward further expanding the flexibility of C-S bonds, with an emphasis on key mechanistic features. The inherent challenges confronting the development of these strategies will be presented, along with the potential application of this chemistry for the synthesis of natural products. Taken together, this knowledge should stimulate impactful improvements on the use of sulfones in catalytic desulfitative C-C and C-X bond formation. A main goal of this article is to bring this technology to the mainstream catalysis practice and to serve as inspiration for new perspectives in catalytic transformation

DFT calculation, a practical tool to predict the electrochemical behaviour of organic electrolytes in aqueous redox flow batteries

Herein, a computational predictive tool for redox flow batteries based on NBO and ADCH charge distribution studies is presented and supported by experimental evidence. Using highly water soluble (>2 M) non-planar 2,2′ - bipyridinium salts as a case of study, this work presents a DFT protocol that successfully predicts the stability and forecasts their potential application as active materials for Aqueous Organic Redox Flow Batteries (AORFB). An initial theoretical-experimental characterization of selected bipyridines served to determine the effect of the ring size, geometry, and electron density on the physico-chemical properties of the materials. Nonetheless, the NBO and ADCH charge analyses were essential tools to understand the stability of the reduced species in terms of electronic delocalization and the importance of the molecular design on the stability of electrolyte for AORFB. Based on these results, the cell performance of seven-membered 2,2′ -bypiridinium salt, (2), and m-Me substituted homologous, (4), were compared. The significantly lower capacity decay rendered by compound 4 based electrolyte, (0.35%/cycle) compared with compound 2 based electrolyte, (0.71%/cycle) was in good agreement with the predicted stability. The aim of this work is to highlight the powerful synergy between DFT calculations and organic chemistry in predicting the behaviour of different negolytesThis work has been funded by the European Union under the HIGREEW project, Affordable High-performance Green Redox Flow batteries (Grant agreement no. 875613). H2020: LC-BAT-4-2019. A.C. Lopes acknowledges the Ramon y Cajal (RYC2021-032277-I) research fellowship, the financial support from Ministerio de Ciencia e Innovacion ´ / AEI /10.13039/501100011033 and from European Union NextGenerationEU/PRTR. We also thank the CCC-UAM (Graforr project) for allocation of computer tim

Design of New Dispersants Using Machine Learning and Visual Analytics

Artificial intelligence (AI) is an emerging technology that is revolutionizing the discovery of new materials. One key application of AI is virtual screening of chemical libraries, which enables the accelerated discovery of materials with desired properties. In this study, we developed computational models to predict the dispersancy efficiency of oil and lubricant additives, a critical property in their design that can be estimated through a quantity named blotter spot. We propose a comprehensive approach that combines machine learning techniques with visual analytics strategies in an interactive tool that supports domain experts’ decision-making. We evaluated the proposed models quantitatively and illustrated their benefits through a case study. Specifically, we analyzed a series of virtual polyisobutylene succinimide (PIBSI) molecules derived from a known reference substrate. Our best-performing probabilistic model was Bayesian Additive Regression Trees (BART), which achieved a mean absolute error of (Formula presented.) and a root mean square error of (Formula presented.), as estimated through 5-fold cross-validation. To facilitate future research, we have made the dataset, including the potential dispersants used for modeling, publicly available. Our approach can help accelerate the discovery of new oil and lubricant additives, and our interactive tool can aid domain experts in making informed decisions based on blotter spot and other key propertie

San Adrian: un nuevo yacimiento de la Edad del Bronce en el Norte de la Peninsula Iberica

Bronze Age studies carried out in the Cantabrian Region have traditionally focused on prestige goods and funerary contexts. As a result of this, the lack of information about daily activities, subsistence strategies, and human settlement on a regional scale is evident in the state of art. However, current research has achieved new discoveries in recent years, allowing a reconstruction of some aspects of the economic structure, settlements, material culture and the palaeoenvironment during the Bronze Age. Indeed, besides the funerary practices discovered in 1983 in San Adrian (Parztuergo Nagusia, Gipuzkoa), research has now revealed the presence of Upper Palaeolithic and Early Bronze Age occupations. This paper presents a first characterization of the retrieved evidence and a preliminary evaluation of the archaeological site and its environment. San Adrian is a tunnel-shaped cave located at 1,000 meters a.s.l. in the Aizkorri mountain range, opening a passage beneath the Atlantic-Mediterranean watershed in northern Iberia. The strategic character of this mountain site is demonstrated by the presence of Upper Palaeolithic and Bronze Age occupations, and by the construction of a road passing through it and the fortification of both its entrances in the Middle Ages. The aim of the archaeological survey started in 2008 was to identify, describe and evaluate the heritage potential of the cave, because previous fieldwork had only managed to make surface finds in the side galleries, including a medieval hoard and Bronze Age human remains. The work carried out by our research group at San Adrian includes a series of test pits and the excavation of an area nine square metres in size following stratigraphic criteria. In the current state, we identified at least two contexts corresponding to Late Upper Palaeolithic and Bronze Age occupations in the cave. Fieldwork included the sieving and flotation of sediment and the collection of samples for different types of analysis: palynology, carpology, sedimentology, and radiocarbon dating. The evidence is being studied by a multidisciplinary team according to expertise requirements for each topic: palaeobotany and environment, archaeozoology, sedimentology, geology, physical anthropology, prehistoric industries (lithics, pottery and bone) and archaeological and historical documentation. Because of its recent discovery, Upper Palaeolithic evidence remains still under study, but first results on Bronze Age layers can be presented. The ongoing archaeobotanical and archaeozoological studies reveal the exploitation of domestic plants and fauna complemented by hunting and foraging of wild species. At the same time, the archaeological artefacts and their production sequences show the exploitation of nearby resources on both sides of the mountain range, while prestige goods are absent. This evidence is also used to estimate the regularity of cave occupations and to propose a model of seasonal exploitation of the mountain environment. The results obtained reveal the exploitation of resources from both the Mediterranean and Atlantic basins, and contribute towards an understanding of the daily activities of Bronze Age societies. In addition, the evidence shows the exchange and circulation of quotidian products between the Cantabrian region and inland Iberia in other networks than those of prestige goods

Dementia care in times of COVID-19: Experience at Fundació ACE in Barcelona, Spain

Background: Fundació ACE is a non-profit organization providing care based on a holistic model to persons with cognitive disorders and their families for 25 years in Barcelona, Spain. Delivering care to this vulnerable population amidst the COVID-19 pandemic has represented a major challenge to our institution. Objective: To share our experience in adapting our model of care to the new situation to ensure continuity of care. Methods: We detail the sequence of events and the actions taken within Fundació ACE to swiftly adapt our face-to-face model of care to one based on telemedicine consultations. We characterize individuals under follow-up by the Memory Unit from 2017 to 2019 and compare the number of weekly visits in 2020 performed before and after the lockdown was imposed. Results: The total number of individuals being actively followed by Fundació ACE Memory Unit grew from 6,928 in 2017 to 8,147 in 2019. Among those newly diagnosed in 2019, most patients had mild cognitive impairment or mild dementia (42% and 25%, respectively). Weekly visits dropped by 60% following the suspension of face-to-face activity. However, by April 24 we were able to perform 78% of the visits we averaged in the weeks before confinement began. Discussion: We have shown that Fundació ACE model of care has been able to successfully adapt to a health and social critical situation as COVID-19 pandemic. Overall, we were able to guarantee the continuity of care while preserving the safety of patients, families, and professionals. We also seized the opportunity to improve our model of care

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Nuevas reacciones de sulfonas a, B- insaturadas mediadas por metales de transición : arilación catalizada por paladio y adición enantioselectiva catalizada por rodio

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura 29-11-200

E/Z Photoisomerization of Olefins as an Emergent Strategy for the Control of Stereodivergence in Catalysis

The stereoselective photoisomerization of olefins via Energy Transfer (EnT) sensitization bears significant potential in the context of rational design of catalytic stereodivergent methodologies. Whereas approaches for controlling the access to E- and Z- isomers depend highly on the nature of the catalyst – and therefore are not easily implemented as a general strategy – EnT catalysis has emerged in recent years as an increasingly powerful tool for olefin geometry control in a nearly perfect step-economic fashion. Moreover, this approach presents both high functional group tolerance and, most notably, has demonstrated ample multicatalytic compatibility. This feature has enabled the development of tandem stereodivergent catalytic strategies, which are the focus of this Review. (Figure presented.)We thank the Ministerio de Ciencia e Innovación (MICINN) and Fondo Europeo de Desarrollo Regional (FEDER, UE) for financial support (Agencia Estatal de Investigación/project PGC2018-098660-B-I00). J. C. thanks the Ministerio de Educación, Cultura y Deportes for a FPU fellowship. We thank Inés Manjón for helpful suggestions. We thank Maria T. Quirós for the design and creation of the TOC graphic of this review. We also thank the referees of this review for their comments, which helped improve the quality of the manuscrip

One-Metal/Two-Ligand for Dual Activation Tandem Catalysis: Photoinduced Cu-Catalyzed Anti-hydroboration of Alkynes

A dual catalyst system based on ligand exchange of two diphosphine ligands possessing different properties in a copper complex has been devised to merge metal- and photocatalytic activation modes. This strategy has been applied to the formal anti-hydroboration of activated internal alkynes via a tandem sequence in which Cu/Xantphos catalyzes the B2pin2-syn-hydroboration of the alkyne whereas Cu/BINAP serves as a photocatalyst for visible light-mediated isomerization of the resulting alkenyl boronic ester. Photochemical studies by means of UV-vis absorption, steady-state and time-resolved fluorescence, and transient absorption spectroscopy have allowed characterizing the photoactive Cu/BINAP species in the isomerization reaction and its interaction with the intermediate syn-alkenyl boronic ester through energy transfer from the triplet excited state of the copper catalyst. In addition, mechanistic studies shed light into catalyst speciation and the interplay between the two catalytic cycles as critical success factorsWe thank the Ministerio de Ciencia e Innovación (MICINN) and Fondo Europeo de Desarrollo Regional (FEDER, UE) for financial support (Agencia Estatal de Investigación/Project PGC2018-098660-B-I00). J.C.C. thanks MECD for a FPU fellowship. This research was also funded by the European Union’s Horizon 2020 research and innovation program under European Research Council (ERC) through the HyMAP project, grant agreement no. 648319. Financial support was received from AEI-MICINN/FEDER, UE through the Nympha Project (PID2019-106315RB-I00

Usefulness of peripapillary nerve fiber layer thickness assessed by optical coherence tomography as a biomarker for Alzheimer’s disease

Abstract The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer’s Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer’s disease’s (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 µm, MCI group: 98,54 ± 14,43 µm and AD group: 96,61 ± 15,27 µm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119), nasal (p = 0,151), superior (p = 0,435) or inferior (p = 0,825) quadrants between AD, MCI and control groups. These results do not support the usefulness of peripapillary RNFL analysis as a marker of cognitive impairment or in discriminating between cognitive groups. The analysis of other OCT measurements in other retinal areas and layers as biomarkers for AD should be tested further