Unveiling Intramolecular [3+2] Cycloaddition Reactions Leading to Functionalized Heterocycles in the Light of Molecular Electron Density Theory.

The relative reactivity and cis/trans selectivity of the intramolecular [3+2] cycloaddition (IM32CA) reactions of nitrile oxide (NO), azide (AZ), nitrile sulfide (NS) and nitrile ylide (NY), leading to functionalized heterocycles are studied within the Molecular Electron Density Theory. The kinetically controlled IM32CA reactions are predicted to be cis stereospecific, while the reaction feasibility follows the order NY>NS>NO>AZ with the respective activation Gibbs free energies of 13.7, 17.

An MEDT Study of the Reaction Mechanism and Selectivity of the Hetero-Diels-Alder Reaction Between 3-Methylene-2,4-Chromandione and Methyl Vinyl Ether.

The hetero-Diels-Alder (HDA) reaction between the ambident heterodiene 3-methylene-2,4-chromandione (MCDO) and non-symmetric methyl vinyl ether (MVE) is investigated using the molecular electron density theory (MEDT) at the B3LYP/6-311G(d,p) computational level. The aim of this study is to gain insight into its molecular mechanism and to elucidate the factors that control the selectivity found experimentally. DFT-based reactivity indices reveal that MCDO exhibits strong electrophilic characteristics, while MVE displays a strong nucleophilic character.

A molecular electron density theory study of the bimolecular nucleophilic substitution reactions on monosubstituted methyl compounds.

The nucleophilic substitution reactions involving methyl monosubstituted compounds have been studied within the Molecular Electron Density Theory (MEDT) at the B97X-D/6-311+G(d,p) computational level in DMSO. This study aims to characterize the electronic nature of the transition state structures (TSs) involved in the so-called S2 and Si reactions. Both electron localization function and atom-in-molecules topological analyses indicate that the TSs involved in these nucleophilic substitutions can be described as a central methyl CH carbocation, which is strongly stabilized by the presence of two neighbouring nucleophilic species through electron density transfer.

Understanding the Electronic Effects of Lewis Acid Catalysts in Accelerating Polar Diels-Alder Reactions.

The electronic effects of Lewis acid (LA) catalysts in reducing the activation energies of polar Diels-Alder (P-DA) reactions have been studied within Molecular Electron Density Theory. To this end, a quantum topological energy partitioning scheme, namely, the Relative Interacting Atomic Energy (RIAE) analysis, is applied to the transition state structures (TSs) and the ground state of the reagents of two different LA-catalyzed P-DA reactions. Analyses of the ξ total energies of the two interacting frameworks (X) show that the electronic energy stabilization of the electrophilic frameworks, resulting from the global electron density transfer (GEDT), is the cause of an effective decrease of the activation energies.

MEDT analysis of mechanism and selectivities in non-catalyzed and lewis acid-catalyzed diels-alder reactions between R-carvone and isoprene.

Within the context of Molecular Electronic Density Theory (MEDT), this study investigates the Diels-Alder reaction among isoprene (2) and R-carvone (1R) applying DFT simulations, with and without Lewis acid (LA) catalysis. The results show that carvone (1R) acts as an electrophile and isoprene (2) as a nucleophile in a polar process. LA catalysis increases the electrophilicity of carvone, thereby improving the reactivity and selectivity of the reaction by reducing the activation Gibbs free energy.

Synthesis, Molecular Electron Density Theory Study, Molecular Docking, and Pharmacological Evaluation of New Coumarin-Sulfonamide-Nitroindazolyl-Triazole Hybrids as Monoamine Oxidase Inhibitors.

Inhibitors of monoamine oxidases (MAOs) are of interest for the treatment of neurodegenerative disorders and other human pathologies. In this frame, the present work describes different synthetic strategies to obtain MAO inhibitors via the coupling of the aminocoumarin core with arylsulfonyl chlorides followed by copper azide-alkyne cycloaddition, leading to coumarin-sulfonamide-nitroindazolyl-triazole hybrids. The nitration position on the coumarin moiety was confirmed through nuclear magnetic resonance spectroscopy and molecular electron density theory in order to elucidate the molecular mechanism and selectivity of the electrophilic aromatic substitution reaction.

Using reservoir computing to construct scarred wave functions.

Scar theory is one of the fundamental pillars in the field of quantum chaos, and scarred functions are a superb tool to carry out studies in it. Several methods, usually semiclassical, have been described to cope with these two phenomena. In this paper, we present an alternative method, based on the novel machine learning algorithm known as reservoir computing, to calculate such scarred wave functions together with the associated eigenstates of the system.

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.

Activation of p53 signaling and regression of breast and prostate carcinoma cells by spirooxindole-benzimidazole small molecules.

This study discusses the synthesis and use of a new library of spirooxindole-benzimidazole compounds as inhibitors of the signal transducer and activator of p53, a protein involved in regulating cell growth and cancer prevention. The text includes the scientific details of the [3 + 2] cycloaddition (32CA) reaction between azomethine ylide and ethylene within the framework of Molecular Electron Density Theory. The mechanism of the 32CA reaction proceeds through a process, with emphasis on the highly asynchronous transition state structure.

Effect of comorbidity and multimorbidity on adherence to follow-up recommendations among long-term breast cancer survivors.

Objectives: To study the impact of comorbidities, multimorbidity, and multimorbidity clusters on adherence to recommended follow-up guidelines among long-term breast cancer survivors.

Study Design: Retrospective cohort study based on 2078 women diagnosed with breast cancer from 2000 to 2006 and followed up from 2012 to 2016.

Main Outcome Measures: Adherence to breast cancer follow-up recommendations (annual medical visit and imaging) was determined.

New spiro-indeno[1,2-]quinoxalines clubbed with benzimidazole scaffold as CDK2 inhibitors for halting non-small cell lung cancer; stereoselective synthesis, molecular dynamics and structural insights.

Despite the crucial role of CDK2 in tumorigenesis, few inhibitors reached clinical trials for managing lung cancer, the leading cause of cancer death. Herein, we report combinatorial stereoselective synthesis of rationally designed spiroindeno[1,2-]quinoxaline-based CDK2 inhibitors for NSCLC therapy. The design relied on merging pharmacophoric motifs and biomimetic scaffold hopping into this privileged skeleton cost-effective one-pot multicomponent [3 + 2] cycloaddition reaction.

Binding affinity predictions with hybrid quantum-classical convolutional neural networks.

Central in drug design is the identification of biomolecules that uniquely and robustly bind to a target protein, while minimizing their interactions with others. Accordingly, precise binding affinity prediction, enabling the accurate selection of suitable candidates from an extensive pool of potential compounds, can greatly reduce the expenses associated to practical experimental protocols. In this respect, recent advances revealed that deep learning methods show superior performance compared to other traditional computational methods, especially with the advent of large datasets.

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

The reaction of -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 position of the -phenyl substituent of iminoborane; and (iii) a formal 1,3-hydrogen shift yielding the final fused aromatic compound.

Taking advantage of noise in quantum reservoir computing.

The biggest challenge that quantum computing and quantum machine learning are currently facing is the presence of noise in quantum devices. As a result, big efforts have been put into correcting or mitigating the induced errors. But, can these two fields benefit from noise? Surprisingly, we demonstrate that under some circumstances, quantum noise can be used to improve the performance of quantum reservoir computing, a prominent and recent quantum machine learning algorithm.

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.

A qualitative exploration of patient safety in a hospital setting in Spain: Policy and practice recommendations on patients' and companions' participation.

Introduction: Patients' and companions' participation in healthcare could help prevent adverse events, which are a significant cause of disease and disability. Before designing interventions to increase participation, it is first necessary to identify attitudes to patient safety. This study aimed to explore patients' and companions' perceptions, attitudes and experiences of patient safety, taking into account contextual factors, such as cultural background, which are not usually captured in the literature.

Novel use of riociguat in infants with severe pulmonary arterial hypertension unable to wean from inhaled nitric oxide.

Introduction: Riociguat, an oral soluble guanylate cyclase stimulator, has been approved for use in adults with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension. However, there is limited data on its therapeutic use in children.

Case Presentation: We report the case of two infants with severe suprasystemic pulmonary hypertension who were successfully treated with riociguat after failure to wean off inhaled nitric oxide (iNO) despite combination PAH therapy.

Drug-related problems in patients admitted for SARS-CoV-2 infection during the COVID-19 pandemic.

Drug-related problems (DRP) are events or circumstances in which drug therapy does or could interfere with desired health outcomes. In December 2019, a new coronavirus, SARS-CoV-2, appeared. Little knowledge about this type of infection resulted in the administration of various drugs with limited use in other pathologies.

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

The [3+2] cycloaddition (32CA) reactions of -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.

Dysphagia in hospitalized patients: Prevalence, related factors and impact on aspiration pneumonia and mortality.

Background: Oropharyngeal dysphagia can be highly concerning in hospitalized patients, increasing morbidity and mortality, making its early identification essential. We aimed to characterize dysphagia and its association with aspiration pneumonia and mortality in a tertiary hospital in Barcelona, Spain.

Methods: Using data from all hospital discharges during the period 2018-2021, we identified the characteristics of patients with dysphagia and their distribution among hospital departments through the minimum data set, which codifies patients' diagnoses according to the International Classification of Diseases 10th Revision (ICD-10).

Optimal quantum reservoir computing for the noisy intermediate-scale quantum era.

Universal fault-tolerant quantum computers require millions of qubits with low error rates. Since this technology is years ahead, noisy intermediate-scale quantum (NISQ) computation is receiving tremendous interest. In this setup, quantum reservoir computing is a relevant machine learning algorithm.

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 B97X-D/6-311G(d,p) level. The topology of the electron localization function (ELF) of this AY allows classifying it as a species characterized by the presence of two monosynaptic basins, integrating a total of 0.76 e, at the C1 carbon.

Design, Synthesis and In Vitro Evaluation of Spirooxindole-Based Phenylsulfonyl Moiety as a Candidate Anti-SAR-CoV-2 and MERS-CoV-2 with the Implementation of Combination Studies.

The search for an effective anti-viral to inhibit COVID-19 is a challenge for the specialized scientific research community. This work investigated the anti-coronavirus activity for spirooxindole-based phenylsulfone cycloadducts in a single and combination protocols. The newly designed anti-SARS-CoV-2 therapeutics spirooxindoles synthesized by [3 + 2] cycloaddition reactions represent an efficient approach.

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 [3+2] cycloaddition (32CA) reactions of cyclic nitrones has been studied within Molecular Electron Density Theory (MEDT) at the B97X-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.