Unstable Compounds Research Articles

Nitrosamine impurities: from raw materials to final drug product.

Nitrosamine impurities: from raw materials to final drug product.

Water-soluble vitamins in honeys of various botanical origin and their change during storage of honey

The richest chemical composition of honey determines its extremely high biological activity. The composition and concentration of bioactive compounds of honey largely depend on its botanical origin, i.e. they are determined by nectar and the pollen chemical composition of the nectariferous plant, on the soil on which they grow, as well as on climate and weather conditions. Along with enzymes and minerals, vitamins are found in honey in small but measurable amounts. Vitamins of honey are mainly represented by B-group vitamins. The content of vitamins in honey varies according to its botanical origin. The following types of honey were used for the study: acacia, sunflower, chestnut, linden, buckwheat. The quantitative determination of water-soluble B-group vitamins (thiamine, riboflavin, pyridoxine, pantothenic acid, nicotinic acid) in honey of various botanical origin was carried out in the accredited laboratory of the direction of chemical and biological research of beekeeping products of the Federal Research Center of Beekeeping by the method of capillary electrophoresis. It was revealed that chestnut and buckwheat honey present the highest levels of water-soluble vitamins content; that confirms the prospects of their use as a source of vitamins. Vitamins are unstable compounds that can be easily destroyed by various factors. Under the impact of daylight, the studied water-soluble vitamins contained in honey are destroyed during storage. The dynamics of changes in the vitamins content was traced during the storage of honey for 12 months in a dark place and in the light. Riboflavin andnicotinic acid, which is significantly reduced, is caracterized by a higher sensitivity to the action of daylight during storage of honey.

Study of Stability and Reactivity of Cyclopolic Acid Compounds and Their Derivatives Using Semi-empirical Methods AM1 and PM3

The semi-empirical method is a method can be selected in computational chemistry. This method can be used to study the stability and reactivity of cyclopolic acid compounds and their derivatives. This method is simple method in optimizing a compound in calculating the parameters possessed by the atom. Cyclopolic acid is an organic compound that can be found in corn and beans. Analysis using two methods on HyperChem Professional application are AM1 and PM3. Analysis Result has shown the that total energy and gradient of each compound do not have significant differences in calculations. As in the structure of 2-formyl-3-(hydroxymethyl)-6-methoxy-5-methylterephthalic acid has a total energy of -80608.1868567 (kcal/mol) and a gradient of 0.0898817 (kcal/mol/Ang) with the AM1 method and total energy of -74935.9180118 (kcal/mol) and a gradient of 0.0874369 (kcal/mol/Ang) with the PM3 method. The stable structure is in the structure of the 2-formyl-3-(hydroxymethyl)-6-methoxy-5-methylterephthalic acid based on the calculation of the total energy and gradient. Meanwhile, according to the calculation of the difference between LUMO-HOMO, it has different results. Where according to the calculation of the energy difference between LUMO-HOMO, the most stable compound structure is the structure of 2-formyl-3-(hydroxymethyl)-4-isocyano-6-metoxy-5-methylbenzoic acid but is not reactive. Likewise, the 2-formyl-4-hidroxy-3-(hydroxymethyl)-6-methoxy-5-methylbenzoic acid, 2-formyl-3-(hydroxymethyl)-6-methoxy-5-methyl-4-(oxo-λ6-methyl)benzoic acid and 2-formyl-3-(hydroxymethyl)-6-methoxy-5-methylterephthalic acid are reactive but unstable compound structure.

Геохимия тяжелых металлов почв урбанизированных ландшафтов зон воздействия металлургических предприятий

The results of studies on the gross content and fractional composition of heavy metals in loamy soils of agro-settlement landscapes, soils of floodplain landscapes of the Voronezh River, as well as sandy soils on sandy terraces of forest and parkland landscapes in the zones affected by Lipetsk metallurgical complexes. It has been established that the bulk of iron in the soils of urban landscapes is represented by sparingly soluble compounds (80–96 %). A significant amount of total cadmium (15–22 %) is connected to the fraction of easily replaced and unstable compounds which determines the element high migration activity. Areas of environmental risk with increased concentrations of heavy metals have been identified which include the flood area of the Voronezh floodplain (Zn, Pb) and the pine forest park landscapes on sandy soils in the affected zone by the Novolipetsk Metallurgical Plant (Zn, Pb, Cd).

Application of sulfoxonium ylide in transition-metal-catalyzed C-H bond activation and functionalization reactions

Sulfoxonium ylides are carbene precursors and safer alternatives for highly reactive and unstable diazo compounds, and they are used extensively in the field of C-H activation. The current review is a collection of recent advancements in transition-metal-catalyzed C(sp2)-H activation using sulfoxonium ylides as precursors. The review emphasizes the use of sulfoxonium ylides as coupling partners for acylmethylation of arenes and heteroarenes. Also, it accounts for the construction of heterocycles employing sulfoxonium ylide as a coupling partner with non-innocent directing groups by C-H activation, acylmethylation followed by intramolecular cyclization in one pot or domino fashion. The review also highlights recent advances in C-H activation reactions using sulfoxonium ylide as a carbenoid-based directing group to construct carbocyclic rings. The review focuses on using sulfoxonium ylide as a coupling partner and directing group, followed by the mode of transformation, scope of the reaction, and the possible mechanistic aspect.

C,C- and C,N-Chelated Organocopper Compounds.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds could advance the rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize unstable organocopper compounds. Bidentate ligands can chelate to the same copper atom via η2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via η1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via μ2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure–reactivity relationships.

2,6-Dimethoxybenzyl Bromide

The unstable title compound has been characterized for the first time. Its melting point, UV, IR, 1H and 13C-NMR and high-resolution mass spectra are presented. The X-ray structure has also been determined and shows a rather long C–Br bond perpendicular to the otherwise planar molecule.

Structure enhancement of energetic materials: A theoretical study of the arylamines to arylpentazoles transformation

A theoretical study of the effect of amines-to-pentazoles transformation on the detonation performance is reported in this paper. A quantitative description of the latter is performed for the general case according to our recently developed compositional criterion evaluation algorithm. It is shown that increments of crystal density and enthalpy of formation are both positive meaning a higher detonation performance of the resulting pentazoles. Since the known arylpentazoles are thermally unstable compounds, a simple descriptor of the thermal stability was revealed (R2 = 0.98), which allowed modeling of new pentazoles with expected thermal stability up to 77 °C. Five the most thermally stable structures were then analyzed using high-level first-principles calculations, which provided negative values of the detonation energy for all ionic compounds; this may allow proposing them as safe gas-forming agents. Meanwhile, the relative gain in detonation energy caused by the studied reaction is always positive and can reach 600%. Thus, we have shown that amines-to-pentazoles transformation is an effective tool for enhancing detonation properties when the resulting compound satisfies the thermal stability criterion. Also, we have demonstrated that aromatic/heterocyclic pentazoles may be considered as self-sufficient materials without further modifications by detachment of the aromatic ring.

Synthesis and Applications of Cyclopropanones and Their Equivalents as Three-Carbon Building Blocks in Organic Synthesis

AbstractCyclopropanone derivatives constitute highly strained cycloalkanones with promising applications as three-carbon building blocks in organic synthesis. Due to the presence of a ketone in such a small ring system, all C–C bonds and the carbonyl group are considered to be labile in suitable conditions, leading to a wide variety of synthetic disconnections, including nucleophilic addition, ring expansion, ring-opening, and (formal) cycloaddition. Despite their synthetic potential, the widespread adoption of cyclopropanones as substrates has been considerably hampered by the difficulties associated with the preparation and storage of such unstable compounds, prompting the development of cyclopropanone surrogates that can equilibrate to the parent ketone in situ via elimination. This review summarizes the syntheses and applications of cyclopropanone derivatives and their equivalents, and offers a perspective of the state of the field as well as its expected future directions.1 Introduction2 Preparation of Cyclopropanones and Their Equivalents2.1 Carbenoid Chemistry2.2 Allene Oxide Rearrangement2.3 Ring Closure by Dehydrohalogenation or Dehalogenation2.4 Photolytic Processes2.5 Miscellaneous Formation of Cyclopropanones2.6 Cyclopropanone Equivalents3 Synthetic Applications of Cyclopropanones and Their Equivalents3.1 Nucleophilic Addition to the Carbonyl Group3.2 Ring Expansion3.3 Ring-Opening3.4 Cycloaddition and Formal Cycloaddition4 Conclusion and Outlook

Effect of alkali additives on desulfurization of syngas during supercritical water gasification of sewage sludge.

Amount of H2S and SO2 were generated during the SCWG of sewage sludge. It is essential to reduce the sulfur concentration in syngas for depth utilization of syngas from SCWG of sewage sludge. The syngas desulfurization ability of five additives (KOH, K2CO3, NaOH, Na2CO3, AC) were tested and the result indicated that K2CO3 had the best syngas desulfurization effect while KOH could significantly promote the yield of syngas at 450°C and 4% loading. Increasing KOH and K2CO3 loading to 12% could reduce around 90% of sulfur in syngas comparing to no additives. The XPS analysis results indicated that alkali additives promoted the cyclization and oxidation of unstable sulfur compounds in raw sludge, which can convert it into stable sulfur compounds such as thiophene, sulfone and sulfate. The sulfur in liquid was mainly in the forms of sulfate, and the effect of alkali and AC additive on sulfur in liquid was relatively weak.

Analogs of the Dopamine Metabolite 5,6-Dihydroxyindole Bind Directly to and Activate the Nuclear Receptor Nurr1.

The nuclear receptor-related 1 protein, Nurr1, is a transcription factor critical for the development and maintenance of dopamine-producing neurons in the substantia nigra pars compacta, a cell population that progressively loses the ability to make dopamine and degenerates in Parkinson's disease. Recently, we demonstrated that Nurr1 binds directly to and is regulated by the endogenous dopamine metabolite 5,6-dihydroxyindole (DHI). Unfortunately, DHI is an unstable compound, and thus a poor tool for studying Nurr1 function. Here, we report that 5-chloroindole, an unreactive analog of DHI, binds directly to the Nurr1 ligand binding domain with micromolar affinity and stimulates the activity of Nurr1, including the transcription of genes governing the synthesis and packaging of dopamine.

Research progress on polysaccharide/protein hydrogels: Preparation method, functional property and application as delivery systems for bioactive ingredients

Some bioactive ingredients in foods are unstable and easily degraded during processing, storage, transportation and digestion. To enhance the stability and bioavailability, some food hydrogels have been developed to encapsulate these unstable compounds. In this paper, the preparation methods, formation mechanisms, physicochemical and functional properties of some protein hydrogels, polysaccharide hydrogels and protein-polysaccharide composite hydrogels were comprehensively summarized. Since the hydrogels have the ability to control the release and enhance the bioavailability of bioactive ingredients, the encapsulation and release mechanisms of polyphenols, flavonoids, carotenoids, vitamins and probiotics by hydrogels were further discussed. This review will provide a comprehensive reference for the deep application of polysaccharide/protein hydrogels in food industry.

Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics.

We show the synthesis of an in vivo stable mercury compound with functionality suitable for radiopharmaceuticals. The designed cyclic bisarylmercury was based on the water tolerance of organomercurials, higher bond dissociation energy of Hg−Ph to Hg−S, and the experimental evidence that acyclic structures suffer significant cleavage of one of the Hg−R bonds. The bispidine motif was chosen for its in vivo stability, chemical accessibility, and functionalization properties. Radionuclide production results in 197(m)HgCl2(aq), so the desired mercury compound was formed via a water‐tolerant organotin transmetallation. The Hg‐bispidine compound showed high chemical stability in tests with an excess of sulfur‐containing competitors and high in vivo stability, without any observable protein interaction by human serum assay, and good organ clearance demonstrated by biodistribution and SPECT studies in rats. In particular, no retention in the kidneys was observed, typical of unstable mercury compounds. The natHg analogue allowed full characterization by NMR and HRMS.

Isolated Cricoid Fracture and Thyroid Hematoma in Blunt Injury of the Neck.

Introduction Blunt trauma to the neck may result in life threatening injuries due to airway compromise. Thyroid Injury in a previously normal gland is rare, so is Isolated Cricoid Fracture. The expanding thyroid hematoma and an unstable larynx compound the effects of compression and lead to sudden deterioration of the patient. Case Report We report the case of young male, who sustained a blunt injury in front of the neck. He developed a swelling in the front of his neck and suddenly deteriorated, needing intubation and airway management. Computed Tomographic imaging of the neck showed thyroid hematoma and fracture of the cricoid ring requiring an emergency hemi thyroidectomy and fixation of the cricoid fracture. Discussion This case brings forth the occurrence of two rare entities, Thyroid hematoma and Isolated Cricoid fracture in the same patient needing expert airway management and exploration.

Revisão sobre cromatografia líquida acoplada à espectrometria de massas aplicada à análise toxicológica de alimentos

A cromatografia líquida de alta eficiência (HPLC) acoplada à espectrometria de massas (EM) constitui-se como uma das mais importantes técnicas analíticas utilizadas na determinação de compostos não voláteis ou instáveis termicamente. A combinação de ambas une a excelência da separação do analito de interesse na matriz através da técnica da cromatografia líquida de alto desempenho, juntamente com a técnica da espectrometria de massas que confirma a identificação química. Dentre as alternativas disponíveis, a espectrometria de massas é a que melhor fornece as informações estruturais necessárias. O acoplamento entre estas duas técnicas dá origem a uma ferramenta analítica robusta, versátil e de grande potencial na análise qualitativa e quantitativa em toxicologia de alimentos. O presente artigo apresenta uma revisão de literatura que tem o objetivo de apresentar os fundamentos da aplicação do acoplamento da Cromatografia Líquida e Espectrometria de Massas na área de análise de alimentos.

A Validated LC-MS/MS Assay for the Simultaneous Quantification of the FDA-Approved Anticancer Mixture (Encorafenib and Binimetinib): Metabolic Stability Estimation.

The concurrent use of oral encorafenib (Braftovi, ENF) and binimetinib (Mektovi, BNB) is a combination anticancer therapy approved by the United States Food and Drug Administration (USFDA) for patients with BRAFV600E/V600K mutations suffering from metastatic or unresectable melanoma. Metabolism is considered one of the main pathways of drug elimination from the body (responsible for elimination of about 75% of known drugs), it is important to understand and study drug metabolic stability. Metabolically unstable compounds are not good as they required repetitive dosages during therapy, while very stable drugs may result in increasing the risk of adverse drug reactions. Metabolic stability of compounds could be examined using in vitro or in silico experiments. First, in silico metabolic vulnerability for ENF and BNB was investigated using the StarDrop WhichP450 module to confirm the lability of the drugs under study to liver metabolism. Second, we established an LC–MS/MS method for the simultaneous quantification of ENF and BNB applied to metabolic stability assessment. Third, in silico toxicity assessment of ENF and BNB was performed using the StarDrop DEREK module. Chromatographic separation of ENF, BNB, and avitinib (an internal standard) was achieved using an isocratic mobile phase on a Hypersil BDS C18 column. The linear range for ENF and BNB in the human liver microsome (HLM) matrix was 5–500 ng/mL (R2 ≥ 0.999). The metabolic stabilities were calculated using intrinsic clearance and in vitro half-life. Furthermore, ENF and BNB did not significantly influence each other’s metabolic stability or metabolic disposition when used concurrently. These results indicate that ENF and BNB will slowly bioaccumulate after multiple doses.

Mineralogical-geochemical study of the anionic competition effect on the octacalcium phosphate reaction into fluorapatite

The unstable compound octacalcium phosphate (OCP) is one of the crystalline precursors of the apatite mineral series composed by hydroxyapatite, fluorapatite and chlorapatite. The feature of OCP to react into apatite, depending on the media conditions, has been mainly exploited for biomedical applications as bone and tooth substitute material. Recently, some important applications of OCP have been documented: e.g. as electrode material for supercapacitors and as fluoride remover reagent for environmental purposes. With the aim of deepening the property of OCP to be the crystalline precursor of apatite and assessing if and how the anionic competition can influence the formation of the different apatite end-members, the OCP → apatite reaction has been here investigated placing 0.223 mmol of OCP in 50 mL aqueous solution with 0.368 mmol of dissolved fluoride, chloride, hydroxyl and carbonate anions (fluoride alone, fluoride with each of the other anions, and all the anions together) at room temperature. The post-experiment analyses of solid and liquid phases, conducted by using XRD, ESEM and ICP-OES, show that fluoride is always the main anion removed from solution during the OCP transformation reaction. The precise mineralogical characterization of solid phases formed, performed using the Rietveld algorithm, shows that fluorapatite is always the main resulting apatitic phase, followed by hydroxyapatite. Taking into account the different application fields of OCP, these results could be significant in better defining the OCP → apatite reaction in aqueous solutions where different competing anions are involved.

Compositional variation of atranorin-related components of lichen Myelochroa leucotyliza dependent on extraction solvent and their quantitative analysis by qHNMR.

Quantitative nuclear magnetic resonance (qNMR) is one of the effective and reliable quantification tools for natural product research. Myelochroa leucotyliza belongs to the genus Myelochroa, a common foliose lichen genus found in the Korean Peninsula, and has not been quantitatively analysed using NMR. Previous chemical studies on M. leucotyliza have been limited to the main components by traditional thin-layer chromatography (TLC) experiments. We explored the stability of atranorin, a major component of M. leucotyliza, in methanol and acetone using NMR and characterised the changes in the chemical profiles of the lichen extracts in methanol and acetone using qNMR. Atranorin transformation in the presence of methanol was analysed using time-dependent proton (1 H)-NMR analysis (600 MHz NMR spectrometer). A 1 H qNMR (qHNMR) method was established using dimethyl sulfone as the internal standard for quantifying the selected components isolated from M. leucotyliza. Homogenous mixtures of the samples were dissolved in deuterated chloroform. Time-dependent 1 H-NMR experiments revealed that atranorin (5) from lichen M. leucotyliza decomposed into atraric acid (1) and methyl haemmatommate (2) in methanol. Four components were identified from M. leucotyliza: 1, 2, usnic acid (4), and 5, and their respective contents were determined using qHNMR. The percentages (w/w) of 1, 2, and 4 in the methanol extract were calculated as 5.66%, 0.69%, and 0.90%, while those of 1, 4, and 5 in the acetone extract were 1.70%, 1.68%, and 19.11%, respectively. We used qHNMR to effectively analyse quantitative compositional variations in two different M. leucotyliza extracts and reliably determined the chemical conversion of the unstable compound atranorin.

Extractive deasphalting as a method of obtaining asphalt binders and low-viscosity deasphalted hydrocarbon feedstock from natural bitumen

The peculiarities of the composition of natural bitumen from Russian Federation deposits give rise to further processing and transportation problems due to necessity of construction of processing units close to their production areas. In order to solve this problem, a method of pretreatment of natural bitumen was proposed, as a result, potential asphalt binders and low-viscosity deasphalted oil suitable for transportation to refineries are produced. Based on experimental data, the optimal conditions for the process were selected. It was recommended to carry out the first stage of crude preparation, namely thermomechanical dehydration of bitumen, with an end-point for distillation of 150 °C. This solved the problem of stable water-hydrocarbon emulsions and further dewatering of bitumen, and excluded the possibility of destruction reactions resulting in more unstable hydrocarbon compounds. At the next stage, it was proposed to carry out the process of deasphalting of bitumen with acetone at a solvent:crude ratio of 3:1. Therefore, production of deasphalted oil, with viscosity close to that of natural crude oil, and asphalt, as a feedstock for the production of universal road bitumen, intended for both summer and winter operating conditions, was shown.

Effects of low temperature on blood-to-plasma ratio measurement.

The blood-to-plasma ratio (Rb ) is an important property of drug candidates. Rb is applied widely in drug discovery to convert plasma pharmacokinetic parameters to the respective parameters in blood and to develop in vitro-in vivo correlations. Some compounds such as prodrugs, soft drugs, and peptide mimetics are unstable in blood, making accurate in vitro Rb measurement challenging, but necessary. Low temperature often reduces the rate of enzymatic and chemical reactions and increases the stability of labile compounds in biomatrices. In this study, the effects of 4°C on Rb measurement were evaluated using a set of structurally diverse compounds with various binding and red blood cell (RBC) transport mechanisms. The results indicate that a 4°C Rb method provides comparable Rb values to the 37°C method for most compounds and can therefore be applied to measure the Rb of unstable compounds in drug discovery. In some rare cases, when compounds have a high affinity to specific RBC components (e.g., carbonic anhydrase), the 4°C method may underestimate Rb. In these specific cases, the use of appropriate inhibitors to stabilize unstable compounds is recommended.