Supramolecular chemistry in solution and solid-gas interfaces: synthesis and photophysical properties of monocolor and bicolor fluorescent sensors for barium tagging in neutrinoless double beta decay.

Translation of photophysical properties of fluorescent sensors from solution to solid-gas environments functionalized surfaces constitutes a challenge in chemistry. In this work, we report on the chemical synthesis, barium capture ability and photophysical properties of two families of monocolor and bicolor fluorescent sensors. These sensors were prepared to capture barium cations that can be produced in neutrinoless double beta decay of Xe-136.

Cycloaddition of Butadiene with Perfluoroethylene: Prediction of a Periselectivity Switch under Pressure.

Defying the common Diels-Alder reactivity, the thermal cycloaddition between butadiene and tetrafluoroethylene (TFE) yields exclusively a [2 + 2] cycloadduct via a stepwise diradical mechanism. Here, we study the possibility of reverting to the normal [4 + 2] reactivity in this reaction under high pressure. DFT calculations using the eXtreme Pressure Polarizable Continuum Model (XP-PCM) suggest a more negative activation volume for the concerted [4 + 2] mechanism than the stepwise [2 + 2] mechanism and predict a switch in periselectivity at 1.

Enantiopure [6]-Azairidahelicene by Dynamic Kinetic Resolution of a Configurationally Labile [4]-Helicene.

A pair of enantiopure [6]-azairidahelicenes incorporating chirality at the metal center and on the helicenic ligand were synthesized by dynamic kinetic resolution (dkr) of a configurationally labile [4]-helicenic ligand (4-(2-pyridyl)-benzo[g]phenanthrene, L1H) using bis-cyclometalated chiral-at-metal only iridium(III) precursors as chiral inductors. The origin of the observed dkr is attributed to the different conformation and stability of diastereomeric reaction intermediates formed during the cyclometalation process. The isolated enantiomers exhibited circularly polarized phosphorescence (CPP), with |g| values of 1.

Dehydration of alcohols catalyzed by copper(II) sulfate: type II dyotropic reactions and stepwise mechanisms.

Dehydration of alcohols in the presence of copper(II) sulfate has been analyzed computationally. Density functional theory (DFT) calculations on selected alcohols indicate that this reaction can take place two possible mechanisms: (a) concerted - although asynchronous - type II dyotropic reactions, or (b) stepwise E1-like processes, in which cleavage of the C-O bond occurs in the first step, followed by proton elimination. Our calculations show the relationship between the initial alcohol structure and the preferred mechanism, which is a type II dyotropic reaction for primary alcohols, whereas a stepwise process is the favored one when stable carbocation intermediates are energetically accessible.

Higher-Order Electrocyclizations in Biological and Synthetic Processes.

In general, electrocyclizations follow the Woodward-Hoffmann's rules of conservation of orbital symmetry. These rules have been extensively verified in low-order processes, both in thermal and photochemical reactions, up to eight π-electrons. However, when the number of π-electrons in the system increases, some deviations of that general rules can be found.

Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis.

Background: Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC.

Aromaticity: Quo Vadis.

Aromaticity is one of the most deeply rooted concepts in chemistry. But why, if two-thirds of existing compounds can be classified as aromatic, is there no consensus on what aromaticity is? σ-, π-, δ-, spherical, Möbius, or all-metal aromaticity… why are so many attributes needed to specify a property? Is aromaticity a dubious concept? This perspective aims to reflect where the aromaticity community is and where it is going.

VAI-B: a multicenter platform for the external validation of artificial intelligence algorithms in breast imaging.

Purpose: Multiple vendors are currently offering artificial intelligence (AI) computer-aided systems for triage detection, diagnosis, and risk prediction of breast cancer based on screening mammography. There is an imminent need to establish validation platforms that enable fair and transparent testing of these systems against external data.

Approach: We developed validation of artificial intelligence for breast imaging (VAI-B), a platform for independent validation of AI algorithms in breast imaging.

Selectivity in Cationic Cyclizations Involving Alkynes: A Computational Study on the Biomimetic Synthesis of Steroids.

Invited for the cover of this issue are Abel de Cózar, Ana Arrieta and Fernando P. Cossío at the University of the Basque Country. The image depicts the evolution of a reactive cation to the corresponding cyclic intermediate in the course of a regio- and stereocontrolled biomimetic cyclization.

Selectivity in Cationic Cyclizations Involving Alkynes: A Computational Study on the Biomimetic Synthesis of Steroids.

Computational studies on the electrophilic cyclization between alkynes and transient carbocations or Lewis-acid-activated epoxides show that the regiochemistry of the reaction depends on the terminal or internal position of the triple bond. Reactants possessing terminal alkynyl groups lead to six-membered rings, whereas internal alkynes yield five-membered rings through 6-endo-dig and 5-exo-dig electrophilic cyclizations, respectively. The regiochemistry of the reaction is not determined by two-electron interactions, but by the minimization of Pauli repulsion.

Synthesis of Bicyclic Hemiacetals Catalyzed by Unnatural Densely Substituted γ-Dipeptides.

The asymmetric synthesis of bicyclic highly substituted tetrahydropyrans is described. The reaction is catalyzed by unnatural γ-dipeptides based on densely substituted l- and d-proline derivatives. This organocatalytic one-pot reaction takes place among a ketone, a nitroalkene, and an aldehyde to yield an octahydro-2-chromene scaffold.

Role of imine isomerization in the stereocontrol of the Staudinger reaction between ketenes and imines.

Computational-experimental analysis has allowed determining that the stereochemistry of the Staudinger reaction between ketenes and imines is strongly associated with the nature of the imine, which affects the two steps of the reaction. The first step, namely the nucleophilic attack of the sp-hybridized nitrogen atom of the imine on the sp-hybridized carbon atom of the ketene, is affected by the energetically accessible isomerization patterns of the imine. The second step consists of a conrotatory electrocyclization of the zwitterionic intermediate formed in the previous step.

Phenanthrene-Extended Phenazine Dication: An Electrochromic Conformational Switch Presenting Dual Reactivity.

The synthesis and isolation of one of the few examples of a π-extended diamagnetic phenazine dication have been achieved by oxidizing a phenanthrene-based dihydrophenazine precursor. The resulting dication was isolated and fully characterized, highlighting an aromatic distorted structure, generated by the conformational change upon the oxidation of the dihydrophenazine precursor, which is also correlated with a marked electrochromic change in the UV-vis spectrum. The aromaticity of the dication has also been investigated theoretically, proving that the species is aromatic based on all major criteria (structural, magnetic, and energetic).

A Synthetic Analog of Resveratrol Inhibits the Proangiogenic Response of Liver Sinusoidal Cells during Hepatic Metastasis.

We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models.

Additive and Emergent Catalytic Properties of Dimeric Unnatural Amino Acid Derivatives: Aldol and Conjugate Additions.

Different densely substituted L- and D-proline esters were prepared by asymmetric (3+2) cycloaddition reactions catalyzed by conveniently selected EhuPhos chiral ligands. The γ-nitro-2-alkoxycarbonyl pyrrolidines thus obtained in either their endo or exo forms were functionalized and coupled to yield the corresponding γ-dipeptides. The catalytic properties of these latter dimers were examined using aldol and conjugate additions as case studies.

Bicolour fluorescent molecular sensors for cations: design and experimental validation.

Molecular entities whose fluorescence spectra are different when they bind metal cations are termed bicolour fluorescent molecular sensors. The basic design criteria of this kind of compound are presented and the different fluorescent responses are discussed in terms of their chemical behaviour and electronic features. These latter elements include intramolecular charge transfer (ICT), formation of intramolecular and intermolecular excimer/exciplex complexes and Förster resonance energy transfer (FRET).

Fluorescent Imidazo[1,2-a]pyrimidine Compounds as Biocompatible Organic Photosensitizers that Generate Singlet Oxygen: A Potential Tool for Phototheranostics.

Photodynamic therapy has been used to treat a variety of diseases, however, there is continuing search for new biocompatible photosensitizers. Herein, we demonstrate for the first time that imidazo[1,2-a]pyrimidine compounds are able to generate singlet oxygen species and can act as photosensitizers in the intracellular environment. Our results show that this class of compounds absorb and emit in the 400-500 nm region, present low cytotoxicity in the dark, are efficiently uptaken by cells, are fluorescent in intracellular medium, and generate singlet oxygen upon irradiation, killing cancer cells within 2 h at low concentration (2.

Fluorescent bicolour sensor for low-background neutrinoless double β decay experiments.

Observation of the neutrinoless double β decay is the only practical way to establish that neutrinos are their own antiparticles. Because of the small masses of neutrinos, the lifetime of neutrinoless double β decay is expected to be at least ten orders of magnitude greater than the typical lifetimes of natural radioactive chains, which can mimic the experimental signature of neutrinoless double β decay. The most robust identification of neutrinoless double β decay requires the definition of a signature signal-such as the observation of the daughter atom in the decay-that cannot be generated by radioactive backgrounds, as well as excellent energy resolution.

Towards a more precise therapy in cancer: Exploring epigenetic complexity.

A plethora of preclinical evidences suggests that pharmacological targeting of epigenetic dysregulation is a potent strategy to combat human diseases. Nevertheless, the implementation of epidrugs in clinical practice is very scarce and mainly limited to haematological malignancies. In this review, we discuss cutting-edge strategies to foster the chemical design, the biological rationale and the clinical trial development of epidrugs.

Synthetic Conjugates of Ursodeoxycholic Acid Inhibit Cystogenesis in Experimental Models of Polycystic Liver Disease.

Background And Aims: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of symptomatic biliary cysts. Current surgical and pharmacological approaches are ineffective, and liver transplantation represents the only curative option. Ursodeoxycholic acid (UDCA) and histone deacetylase 6 inhibitors (HDAC6is) have arisen as promising therapeutic strategies, but with partial benefits.

Stepwise Mechanism for the Bromination of Arenes by a Hypervalent Iodine Reagent.

A mild, metal-free bromination method of arenes has been developed using the combination of bis(trifluoroacetoxy)iodobencene and trimethylsilyl bromide. In situ-formed dibromo(phenyl)-λ3-iodane (PhIBr) is proposed as the reactive intermediate. This methodology using PIFA/TMSBr has been applied with success to a great number of substrates (25 examples).

Selective synthesis of trisubstituted pyrroles through the reactions of alkynyl Fischer carbene complexes with oxazolones.

An efficient and simple synthesis of novel trisubstituted 1H-pyrroles 4a-qvia 1,3-dipolar cycloaddition of Δ3-trifluoromethyloxazolones 2a-d with both chromium and tungsten alkynyl Fischer carbene complexes (1a-h) is described. An unexpected and unreported -CF3 group elimination process was observed in the pyrrole structure. Our experimental and theoretical data suggested that the metal fragment may be responsible for this phenomenon.

Discovering Biomolecules with Activity: Designed Repeat Proteins as Biocatalysts for (3 + 2) Cycloadditions.

Designed repeat proteins catalyze the 1,3-dipolar reaction between an imine and a π-deficient dipolarophile in THF solution to form unnatural nitroproline esters, a reaction that no enzyme can catalyze. NMR studies and mutation experiments show that both acidic and basic residues can catalyze the reaction. The diastereocontrol of the reaction depends on the flexibility of the protein and on the number and location of the active lysine and glutamate residues, which can participate independently or forming dyads that promote the formation of unusual diastereomeric cycloadducts.

Bio-inspired Total Synthesis of Twelve Securinega Alkaloids: Structural Reassignments of (+)-Virosine B and (-)-Episecurinol A.

The so-called Securinega alkaloids constitute a class of tetracyclic biologically active specialised metabolites isolated principally from subtropical plants belonging to the Phyllanthaceae family. Following a strategy based on alternative hypotheses for their biosynthesis, an easy and time-efficient divergent synthesis enabled access to twelve of those alkaloids featuring (neo)(nor)securinane skeletons. Moreover, this work permitted to reassign the absolute configurations of (+)-virosine B and (-)-episecurinol A.

Synthesis of Sultones from Chlorosulfates by a Complex Cascade Reaction Occurring under Mild Thermal Conditions.

Chlorosulfate derivatives are interesting reagents that have been traditionally used to get other sulfur-containing compounds by formal nucleophilic substitution of the chlorine atom. This work describes a different mode of reactivity of alkyne-containing chlorosulfates to get sultones, the sulfur analogues of lactones. The complex skeletal rearrangement observed in this transformation is comparable to those intricate processes promoted or catalyzed by organometallic compounds.