Electrochemical Synthesis of 3-(Sulfonyl)quinol-4-ones from -Alkynyl--(formyl)anilides and Sulfinates.

Electrolysis of -alkynyl--(formyl)anilides and sodium sulfinates on graphite electrodes delivers biologically sound 3-(sulfonyl)quinol-4-ones with moderate to good yields. The reaction is carried out in an undivided cell in the presence of silver(I) oxide with potassium iodide or sodium tetrafluoroborate as the supporting electrolyte. The reaction tolerates variously substituted anilides as well as aryl and alkyl sulfinates.

Nature-Inspired 1-Phenylpyrrolo[2,1-]isoquinoline Scaffold for Novel Antiproliferative Agents Circumventing P-Glycoprotein-Dependent Multidrug Resistance.

Previous studies have shown that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in some tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, several novel substituted 1-Ph-DHPIQ derivatives were synthesized which carry carboxylate groups (COOH, COOEt), nitrile (CN) and Mannich bases (namely, morpholinomethyl derivatives) in the C2 position, as replacements of the already reported aldehyde group. They were evaluated for antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and for the ability of selectively inhibiting P-gp-mediated MDR.

Concise and Free-Metal Access to Lactone-Annelated Pyrrolo[2,1-]isoquinoline Derivatives via a 1,2-Rearrangement Step.

Here, An efficient approach to obtaining previously unknown furo[2',3':2,3]pyrrolo[2,1-]isoquinoline derivatives from readily available 1-R-1-ethynyl-2-vinylisoquinolines is described. The reaction features a simple procedure, occurs in hexaflouroisopropanol and does not require elevated temperatures. It has been found that the addition of glacial acetic acid significantly increases the yields of the target spirolactone products.

Pseudo Four-Component Synthesis of 5,6-Dihydroindolo[2,1-]isoquinolines.

An easy synthesis of novel highly functionalized 5,6-dihydroindolo[2,1-]isoquinolines was developed via a pseudo four-component domino reaction of 1-aroyl-3,4-dihydroisoquinolines, terminal α,β-ynones, and malononitrile. The selective formation of this biologically relevant heterocyclic core was achieved using a one-pot approach under microwave irradiation. The formation of the same skeleton through the reaction of 5,6-dihydropyrrolo[2,1-]isoquinolines with malonic acid dinitrile supports the proposed mechanism, involving the intermediate product of the three-component reaction.

Oscillatory Responses to Tactile Stimuli of Different Intensity.

Tactile perception encompasses several submodalities that are realized with distinct sensory subsystems. The processing of those submodalities and their interactions remains understudied. We developed a paradigm consisting of three types of touch tuned in terms of their force and velocity for different submodalities: discriminative touch (haptics), affective touch (C-tactile touch), and knismesis (alerting tickle).

Development and Initial Validation of the Russian Version of the RAADS-14: A Self-Report Questionnaire to Assess Autistic Traits.

Autism is a relatively common neurodevelopmental condition that affects social communication and behavior, affecting the overall quality of life. The prevalence of autism is constantly increasing, but timely diagnosis allows for effective treatment. The aim of our research was to construct a Russian version of the RAADS-14, a brief self-report questionnaire originally designed for autism screening, and to perform its initial validation to provide a reference point in developing autism self-assessment tools for the Russian-speaking population.

Divergent and Nucleophile-Assisted Rearrangement in the Construction of Pyrrolo[2,1-b][3]benzazepine and Pyrido[2,1-a]isoquinoline Scaffolds.

Under microwave (MW) irradiation at 150 °C in toluene and in the presence of nucleophiles (DMAP, triphenylphosphine and tetrahydrothiophene) 1-substituted 1-ethynyl-2-vinyldi- and tetrahydroisoquinolines undergo [3,3]-sigmatropic rearrangement providing pyrrolo[2,1-b][3]benzazepines in good yields. The replacement of toluene with acetonitrile directs the rearrangement towards the formation of 7,11b-dihydro-6H-pyrido[2,1-a]isoquinolines.

Azo Coupling of Indoles Revisited: Synthesis of Biindolyl Photoswitches via the Azo-Coupling/C-H Functionalization Domino Approach.

When azo coupling of aryldiazonium salts with indoles was carried out in aprotic nonpolar solvent on air, a pseudo-three-component reaction has been discovered. Azo coupling is followed by a nucleophilic addition of a second indole unit to the indolium intermediate; aromatization and oxidation are achieved under air.

Salivary Oxytocin and Antioxidative Response to Robotic Touch in Adults with Autism Spectrum Disorder.

Individuals with ASD are known to have a tendency to have tactile sensory processing issues that could be associated with their impairment as regards social communication. The alterations in tactile processing in autistic subjects are usually accompanied by hypersensitivity and other unpleasant emotions induced by tactile contact. In our study, we investigated the impact of the velocity and the force of a tactile stroke received impersonally by a custom-built robotic device.

Domino Approach for the Synthesis of Pyridinium Salts and 1,2,3,8-Tetrahydroimidazo[1,2-]pyridines from 2-Imidazolines and Propiolic Acid Esters.

Adducts of 1-alkyl-2-imidazolines and two molecules of alkyl propiolate, possessing an -propargyl-β-enaminoester fragment, easily undergo a domino reaction to form pyridinium salts with β-(alkylammonio)ethyl group at the nitrogen atom in the presence of 2 equiv of a protic acid. Treatment of the above reaction mixture with a base gives 1,2,3,8-tetrahydroimidazo[1,2-]pyridines. Reaction of the latter compounds with acid chlorides affords pyridinium salts with β-(alkylamido)ethyl moiety at the nitrogen atom.

Investigating the Underutilization of Uterine Fibroid Embolization by Surveying Practice Preferences of Obstetricians/Gynecologists.

This study aimed to survey the practice preferences of obstetricians/gynecologists (OB/GYNs) that may be contributing to the underutilization of uterine fibroid embolization (UFE) in the treatment of symptomatic uterine fibroids (SUFs). A 22-question survey was created using the Qualtrics XM software and distributed to an obstetrics/gynecology-specific social media group of resident or attending OB/GYNs practicing in the United States. One hundred twelve responses met the inclusion criteria.

Photoredox-Catalyzed Chlorotrifluoromethylation of Arylallenes: Synthesis of a Trifluoromethyl Building Block.

A new class of trifluoromethyl building blocks─2-trifluoromethyl allyl chlorides─have been obtained through a photoredox-catalyzed chlorotrifluoromethylation of aryl allenes. The reaction proceeded in a regio- and stereoselective manner. A trifluoromethylated analog of the flunarizine drug was synthesized.

Electrochemical Decarbonylative Aminosulfonylation of Alkynes with Sulfinates and -(Formyl)anilides.

An unprecedented electrochemical three-component reaction of phenylacetylene, sulfinate, and -(formyl)anilide was discovered. The transformation occurs in an undivided cell with a graphite anode and cathode in DMF in the presence of tetrabutylammonium iodide as an electrolyte. The addition of silver(I) oxide and catalytic amounts of iodine facilitated the reaction significantly.

Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity.

Transformations of 1-methoxymethylethynyl substituted isoquinolines triggered by terminal alkynes in alcohols were studied and new 3-benzazecine-containing compounds synthesized, such as 6-methoxymethyl-3-benzazecines incorporating an endocyclic C6-C8 allene fragment and the -ylidene derivatives 6-methoxymethylene-3-benzazecines. The reaction mechanisms were investigated and a preliminary in vitro screening of their potential inhibitory activities against human acetyl- and butyrylcholinesterases (AChE and BChE) and monoamine oxidases A and B (MAO-A and MAO-B) showed that the allene compounds were more potent than the corresponding -ylidene ones as selective AChE inhibitors. Among the allenes, (R = CHOMe) was found to be a competitive AChE inhibitor with a low micromolar inhibition constant value ( = 4.

Chemoselective Divergent Transformations of -(Propargyl)indole-2-carbonitriles with Nitrogen Nucleophiles: Alkyne Hydroamination or Domino Cyclizations.

Interactions of -(propargyl)indole-2-carbonitriles with nitrogen nucleophiles were studied. It was found that lithium hexamethyldisilazane (LiHMDS)-promoted reactions give mixtures of two product types, originating from an initial attack onto carbon-carbon or carbon-nitrogen triple bonds. Performing the reaction at reduced temperature and in the presence of catalytic amounts of LiHMDS delivered alkyne hydroamination products exclusively.

Assembly of 1,2,3,4-Tetrahydropyrrolo[1,2-]pyrazines via the Domino Reaction of 2-Imidazolines and Terminal Electron-Deficient Alkynes.

The transformation of 2-imidazolines into 1,2,3,4-tetrahydropyrrolo[1,2-]pyrazines has been realized. A pseudo-three-component reaction of 2-imidazolines with terminal electron-deficient alkynes (2 equiv) first generates imidazolidines, containing an -vinylpropargylamine fragment. The latter can then undergo a base-catalyzed domino aza-Claisen rearrangement/cyclization reaction sequence, simultaneously constructing pyrrole and pyrazine rings.

A Three-Component Synthesis of 3-Functionally Substituted 5,6-Dihydropyrrolo[2,1-a]isoquinolines.

Synthesis of novel C3-substituted 5,6-dihydropyrrolo[2,1-a]isoquinolines via a three-component domino reaction of 1-aroyl-3,4-dihydroisoquinolines, terminal alkynes and CH-acids under microwave irradiation in dry acetonitrile is described. The method developed enables the obtainment of highly functionalized compounds with pharmacophore groups, which are potentially biologically active.

Synthesis of 8-phenyl substituted 3-benzazecines with allene moiety, their thermal rearrangement and evaluation as acetylcholinesterase inhibitors.

Various 4'-R-substituted phenyl azacyclic allenes were synthesized in good yields, and their thermal transformations were studied. For the first time, the obtained rearrangement products-new N-bridged cyclopenta[a]indenes, and the corresponding parent allenes were evaluated as potential inhibitors of acetyl- and butyrylcholinesterase. Among the tested compounds, the allene derivative 2g proved to competitively inhibit human AChE with inhibition constant value (K) in the low micromolar range.

Two-Stage Seebeck Effect in Charged Colloidal Suspensions.

We discuss the peculiarities of the Seebeck effect in stabilized electrolytes containing the colloidal particles. Its unusual feature is the two stage character, with the linear increase of differential thermopower as the function of colloidal particles concentration n⊙ during the first stage ("initial state") and dramatic drop of it at small n⊙ during the second one ("steady state"). We show that the properties of the initial state are governed by the thermo-diffusion flows of the mobile ions of the stabilizing electrolyte medium itself and how the colloidal particles participate in the formation of the electric field in the bulk of the suspension.

Homobivalent Lamellarin-Like Schiff Bases: In Vitro Evaluation of Their Cancer Cell Cytotoxicity and Multitargeting Anti-Alzheimer's Disease Potential.

Marine alkaloids belonging to the lamellarins family, which incorporate a 5,6-dihydro-1-phenylpyrrolo[2,1-]isoquinoline (DHPPIQ) moiety, possess various biological activities, spanning from antiviral and antibiotic activities to cytotoxicity against tumor cells and the reversal of multidrug resistance. Expanding a series of previously reported imino adducts of DHPPIQ 2-carbaldehyde, novel aliphatic and aromatic Schiff bases were synthesized and evaluated herein for their cytotoxicity in five diverse tumor cell lines. Most of the newly synthesized compounds were found noncytotoxic in the low micromolar range (<30 μM).

Away from Flatness: Unprecedented Nitrogen-Bridged Cyclopenta[]indene Derivatives as Novel Anti-Alzheimer Multitarget Agents.

Nature-inspired, bridged polycyclic molecules share low similarity with currently available drugs, containing preferentially planar and/or achiral moieties. This "Escape from Flatland" scenario, aimed at exploring pharmacological properties of atypical molecular scaffolds, finds interest in synthetic routes leading to tridimensional-shaped molecules. Herein we report on the synthesis of -bridged cyclopenta[]indene derivatives, achieved through microwave-assisted thermal rearrangement of allene 3-benzazecines with high diastereoselectivity.

The Ohm Law as an Alternative for the Entropy Origin Nonlinearities in Conductivity of Dilute Colloidal Polyelectrolytes.

We discuss the peculiarities of the Ohm law in dilute polyelectrolytes containing a relatively low concentration n ⊙ of multiply charged colloidal particles. It is demonstrated that in these conditions, the effective conductivity of polyelectrolyte is the linear function of n ⊙ . This happens due to the change of the electric field in the polyelectrolyte under the effect of colloidal particle polarization.

Proposed Model of the Giant Thermal Hall Effect in Two-Dimensional Superconductors: An Extension to the Superconducting Fluctuation Regime.

We extend the thermodynamic approach for the description of the thermal Hall effect in two-dimensional superconductors above the critical temperature, where fluctuation Cooper pairs contribute to the conductivity, as well as in disordered normal metals where the particle-particle channel is important. We express the Hall heat conductivity in terms of the product of temperature derivatives of the chemical potential and of the magnetization of the system. Based on this general expression, we derive the analytical formalism that qualitatively reproduces the superlinear increase of the thermal Hall conductivity with the decrease of temperature observed in a large variety of experimentally studied systems [Grissonnanche et al.