Cyanoacetohydrazide as a Novel Derivatization Agent for the Determination of UHPLC-HRMS Steroids in Urine.

The possibility of cyanoacetohydrazide usage as a novel derivatizing agent is demonstrated in the presented article, and a comparison with hydroxylamine as the most commonly used reagent is provided. Optimal conditions for steroid derivatization with cyanoacetohydrazide are provided. According to the collected data, the maximum yield of derivatives was observed at pH 2.

From a humorous post to a detailed quantum-chemical study: isocyanate synthesis revisited.

Isocyanates play an essential role in modern manufacturing processes, especially in polyurethane production. There are numerous synthesis strategies for isocyanates both under industrial and laboratory conditions, which do not prevent searching for alternative highly efficient synthetic protocols. Here, we report a detailed theoretical investigation of the mechanism of sulfur dioxide-catalyzed rearrangement of phenylnitrile oxide into phenyl isocyanate, which was first reported in 1977.

6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies.

New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N'-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or via a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalondianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichloro- phenyl)-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was confirmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computational scheme.

Structure and Neuroprotector Properties of a Complex Compound of Lithium with Comenic Acid.

The structure, antioxidant and neuroprotective properties of lithium comenate (lithium 5-hydroxy-4-oxo-4H-pyran-2-carboxylate) were studied. Lithium comenate was obtained by reacting comenic acid (HCom) with lithium hydroxide in an aqueous solution. The structure of lithium comenate was confirmed via thermal analysis, mass spectrometry, IR, NMR and UV spectroscopy.

Study of the Magnesium Comenate Structure, Its Neuroprotective and Stress-Protective Activity.

The crystal structure and the biological activity of a new coordination compound of magnesium ions with comenic acid, magnesium comenate, was characterized and studied. Quantitative and qualitative analysis of the compound was investigated in detail using elemental X-ray fluorescent analysis, thermal analysis, IR-Fourier spectrometry, UV spectroscopy, NMR spectroscopy, and X-ray diffraction analysis. Based on experimental analytical data, the empirical formula of magnesium comenate [Mg(HCom)(HO)]·2HO was established.

New 6'-Amino-5'-cyano-2-oxo-1,2-dihydro-1'-spiro[indole-3,4'-pyridine]-3'-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity.

The purpose of this work was to prepare new isatin- and monothiomalondiamide-based indole derivatives, as well as to study the properties of the new compounds. The four-component reaction of 5-R-isatins (R = H, CH), malononitrile, monothiomalonamide (3-amino-3-thioxo- propanamide) and triethylamine in hot EtOH yields a mixture of isomeric triethylammonium 6'-amino-3'-(aminocarbonyl)-5'-cyano-2-oxo-1,2-dihydro-1'- and 6'-amino-3'-(aminocarbonyl)- 5'-cyano-2-oxo-1,2-dihydro-3'-spiro[indole-3,4'-pyridine]-2'-thiolates. The reactivity and structure of the products was studied.

Phthalylglycyl Chloride as a Derivatization Agent for UHPLC-MS/MS Determination of Adrenaline, Dopamine and Octopamine in Urine.

Dopamine, adrenaline and octopamine are small polar molecules that play a vital role in regulatory systems. In this paper, phthalylglycyl chloride was proposed as a derivatization agent for octopamine, adrenaline and dopamine determination in urine for the first time. The derivatization procedure facilitated the use of reversed-phase liquid chromatography with positive electrospray ionization-high-resolution mass spectrometry.

Alkyl 4-Aryl-6-amino-7- phenyl-3-(phenylimino)-4,7-dihydro- 3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxylates: Synthesis and Agrochemical Studies.

The reaction between dithiomalondianilide (N,N'-diphenyldithiomalondiamide) and alkyl 3-aryl-2-cyanoacrylates in the presence of morpholine in the air atmosphere leads to the formation of alkyl 6-amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]- pyridine-5-carboxylates in 37-72% yields. The same compounds were prepared in 23-65% yields by ternary condensation of aromatic aldehydes, ethyl(methyl) cyanoacetate and dithiomalondianilide. The reaction mechanism is discussed.

The Reactions of N,N'-Diphenyldithiomalondiamide with Arylmethylidene Meldrum's Acids.

The Michael addition reaction between dithiomalondianilide (N,N'-diphenyldithiomalondiamide) and arylmethylidene Meldrum's acids, accompanied by subsequent heterocyclization, was investigated along with factors affecting the mixture composition of the obtained products. The plausible mechanism includes the formation of stable Michael adducts which, under the studied conditions, undergo further transformations to yield corresponding N-methylmorpholinium 4-aryl-6-oxo-3-(N-phenylthio-carbamoyl)-1,4,5,6-tetrahydropyridin-2-thiolates and their oxidation derivatives, 4,5-dihydro-3H-[1,2]dithiolo[3,4-b]pyridin-6(7H)-ones. The structure of one such product, N-methylmorpholinium 2,2-dimethyl-5-(1-(2-nitrophenyl)-3-(phenylamino)-2-(N-phenylthiocarbamoyl)-3-thioxopropyl)-4-oxo-4H-1,3-dioxin-6-olate, was confirmed via X-ray crystallography.

2-Amino-4,5-dihydrothiophene-3-carbonitriles: A New Synthesis, Quantum Chemical Studies, and Mannich-Type Reactions Leading to New Hexahydrothieno[2,3-d]pyrimidines.

-2-Amino-4-aryl-5-benzoyl-4,5-dihydrothiophene-3-carbonitriles were prepared either by the reaction of 3-aryl-2-cyanothioacrylamides with α-thiocyanatoacetophenone or by the Michael-type addition of cyanothioacetamide to α-bromochalcones followed by intramolecular cyclization. The mechanism of the first reaction was studied using high-level quantum chemical calculations. Density functional theory (DFT) studies were carried out to determine the mechanism of the first reaction.

Recognition capabilities of a Hopfield model with auxiliary hidden neurons.

We study the recognition capabilities of the Hopfield model with auxiliary hidden layers, which emerge naturally upon a Hubbard-Stratonovich transformation. We show that the recognition capabilities of such a model at zero temperature outperform those of the original Hopfield model, due to a substantial increase of the storage capacity and the lack of a naturally defined basin of attraction. The modified model does not fall abruptly into the regime of complete confusion when memory load exceeds a sharp threshold.

Unusual Oxidative Dimerization in the 3-Aminothieno[2,3-]pyridine-2-carboxamide Series.

Noncatalyzed, regio- and stereoselective hypochlorite oxidation of 3-aminothieno[2,3-]pyridine-2-carboxamides is presented. Unexpectedly, the oxidation proceeded by different mechanistic pathways, and different products were formed, depending on the nature of solvents used. A possible mechanism, the structure of products, kinetics and dynamics of intramolecular processes, and biological activity of products are discussed.

Probing chemical space of tick-borne encephalitis virus reproduction inhibitors with organoselenium compounds.

Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is the leading cause of arboviral neuroinfections in Europe. Only a few classes of the nucleoside and non-nucleoside inhibitors were investigated against TBEV reproduction. Paving the way to previously unexplored areas of anti-TBEV chemical space, we assessed the inhibition of TBEV reproduction in the plaque reduction assay by various compounds derived from cyanothioacetamide and cyanoselenoacetamide.

Self-averaging in the random two-dimensional Ising ferromagnet.

We study sample-to-sample fluctuations in a critical two-dimensional Ising model with quenched random ferromagnetic couplings. Using replica calculations in the renormalization group framework we derive explicit expressions for the probability distribution function of the critical internal energy and for the specific heat fluctuations. It is shown that the disorder distribution of internal energies is Gaussian, and the typical sample-to-sample fluctuations as well as the average value scale with the system size L like ∼Llnln(L).

2,2,2-Trifluoroethyl-thiadiazines: a patent evaluation of WO2016023927.

The Alzheimer's disease (AD) is acknowledged as the most common type of dementia in aging adults. It is characterized by the formation of intracellular neurofibrillary tangles and extracellular amyloid plaques. The latter insoluble deposits mainly consist of β-amyloid peptides (Aβ), which are the derivatives of the amyloid precursor protein (APP).

Universal free-energy distribution in the critical point of a random Ising ferromagnet.

We discuss the non-self-averaging phenomena in the critical point of weakly disordered Ising ferromagnet. In terms of the renormalized replica Ginzburg-Landau Hamiltonian in dimensions D<4, we derive an explicit expression for the probability distribution function (PDF) of the critical free-energy fluctuations. In particular, using known fixed-point values for the renormalized coupling parameters, we obtain the universal curve for such PDF in the dimension D=3.

Design and synthesis of pyrido[2,1-b][1,3,5]thiadiazine library via uncatalyzed Mannich-type reaction.

This Research Article describes the synthesis of an over 700-member library of (8R/8S)-3-R-8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazin-9-carbonitriles by uncatalyzed Mannich-type reaction of N-methylmorpholinium (4R/4S)-4-aryl-3-cyano-6-oxo-1,4,5,6-tetrahydropyridin-2-thiolates with a set of primary amines and excessive HCHO. The scope and limitations of the reaction were studied. Starting thiolates were obtained in yields of 53-82% by multicomponent reaction of aromatic aldehydes, cyanothioacetamide, 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid), and N-methylmorpholine, followed by heterocyclization of the resulting Michael adducts.

Inhibitors of tick-borne flavivirus reproduction from structure-based virtual screening.

Flaviviruses form a large family of enveloped viruses affecting millions of people over the world. To date, no specific therapy was suggested for the infected people, making the treatment exclusively symptomatic. Several attempts were performed earlier for the design of fusion inhibitors for mosquito-borne flaviviruses, whereas for the tick-borne flaviviruses such design had not been performed.

Two-temperature Langevin dynamics in a parabolic potential.

We study a planar two-temperature diffusion of a Brownian particle in a parabolic potential. The diffusion process is defined in terms of two Langevin equations with two different effective temperatures in the X and the Y directions. In the stationary regime the system is described by a nontrivial particle position distribution, P(x,y), which we determine explicitly.

A chemical placebo: NaCl as an effective, cheapest, non-acidic and greener catalyst for Biginelli-type 3,4-dihydropyrimidin-2(1H)-ones (-thiones) synthesis.

Despite prior reports of several really effective catalytic and non-catalytic approaches towards Biginelli's 3,4-dihydropyrimidin-2(1H)-ones, an overwhelming number of new catalysts for the Biginelli reaction have been recently published. Most of the catalysts are somewhat exotic, expensive, harmful and even uneffective in the absence of acidic additives. Herein we reduce the "yet-another-one-catalyst" idea to absurdity by proposing NaCl promotes the reaction that actually requires no catalyst, neither rare nor expensive.