Lack Of Reactivity Research Articles

Gas-phase reactivity of sulfate esters and analogs: Why is the sulfur center unreactive?

Sulfate esters and analogs are important species in synthetic chemistry, in processes catalyzed by sulfatases and in atmospheric chemistry because of their role as precursors in the formation of aerosols. In order to understand the intrinsic reactivity of these systems toward simple nucleophiles and the lack of reactivity in the sulfur center, calculations were carried out for (MeO)2SO2, MeS(OMe)O2 and (MeO)2SO reacting with OH−, NH2−, SH−, F−, MeO− and EtO− at the B3LYP/6-311+G(3df,2p) level of theory. Our results are in agreement with previous experimental gas-phase studies that showed substitution at the C atom (SN2@C) and elimination promoted by abstraction of a proton followed by release of formaldehyde (ECO2) to be the main reaction channels for dimethyl sulfate and sulfite, and proton transfer (PT) for methyl methanesulfonate. Our calculations show that the barriers for substitution at the S atom (SN2@S) are comparable, and sometimes even lower in energy, than the barriers calculated for the SN2@C pathway for strong nucleophiles such as OH− and NH2−. Yet, SN2@S reactions are only observed in a few cases in dimethyl sulfite in reactions promoted by delocalized carbanions. Calculations that map out the energy profile of the nucleophile approaching the C and S center reveal a much more favorable energy pathway for reaction at the C center due to the electrostatic repulsion of the oxygens surrounding the S center. Therefore, reactivity at the S center in these systems is dictated by a delicate balance between the reaction dynamics and the thermochemistry of these systems and attack of strong nucleophiles at the S center, although thermochemically favorable, is dynamically hindered and thus promote crossing over to the C route pathway.

Au as an efficient promoter for electrocatalytic oxidation of formic acid and carbon monoxide: a comparison between Pt-on-Au and PtAu alloy catalysts

The absence of unpaired d-electrons of gold leads to its lack of reactivity and paucity of catalytic activity. Synergistic activity of bimetallic PtAu has been proved, and its structure greatly influences on the electrocatalytic activity toward formic acid and carbon monoxide oxidation. Here, a comparison between Pt-modified Au (designated as Pt-on-Au) and PtAu alloy catalysts has been studied. The Pt-on-Au catalyst was prepared by electrodeposition of Pt on the pre-prepared Au, while PtAu alloy was obtained by co-electrodeposition. As a whole, both types of PtAu catalysts were found to be more active toward formic acid electrooxidation compared to pure Pt, exhibiting maximum activity on Pt-on-Au catalyst with Pt to Au atomic ratio of 1:10.22. Moreover, the Pt/Au atomic ratio directly relates to the oxidation pathway of formic acid and carbon monoxide oxidation. The results may be ascribed to much less COads on the surface than single Pt catalyst due to the effect of Au nanoparticles. CO stripping voltammograms present the obvious variation between Pt-on-Au and PtAu alloy catalysts. Meanwhile, the electrocatalytic activities of bimetallic PtAu are evaluated by electrochemical impedance spectroscopy and Tafel analysis.

Facile B–H Bond Activation of Borane by Stable Carbenoid Species

Stable nucleophilic carbene compounds have recently been shown to be able to mimic in some instances the reactivity of metal fragments in the reaction of unactivated E-H bonds (E = H, R3Si, NH2, R2P). However, the insertion into a B-H bond of the strongly Lewis acidic BH3 molecule has never been observed at a single C atom or even at a metal fragment. Our results show that designed stable, highly electrophilic carbenoid fragments in compounds 4 and 6 can achieve this reactivity in a controlled manner. Density functional theory calculations corroborated the experimental results on the presently designed systems as well as the lack of reactivity on nucleophilic carbenes.

CCN1 expression in interleukin-6 deficient mouse kidney in experimental model of heart failure

Chronic heart failure often leads to worsening of the renal function. Mediators of this process include inflammatory and neuroendocrine factors. CCN1 (Cyr 61), a member of growth factor-inducible immediate early genes, which modulates inflammation and fibrogenesis, is excreted with urine in the early phase of acute renal injury and may be involved in the pathogenesis of the cardiorenal syndrome. The aim of the study was to evaluate CCN1 protein abundance and localization in the kidney of IL-6-deficient C57BL/6J (IL-6 KO) mice and respective wild-type (WT) animals in basal conditions and in animals with chronic heart failure twelve weeks after myocardial infarction. Age- and sex-matched mice from both strains subjected to sham operation served as controls. One group of WT animals subjected to myocardial infarction was treated with antagonist of AT1 receptor telmisartan over 12 weeks. Abundance and localization of CCN1 protein in kidney were assessed with Western blotting and immunohistochemistry, respectively. In all groups the strongest immunohistochemical reaction for CCN1 was observed in distal convoluted tubules and in smaller arteries, however, the total expression of CCN1 protein was lower in IL-6 KO mice in comparison to WT animals. The main difference in CCN1 distribution between the examined genotypes was lack of reaction in internal renal medulla and very weak reaction in proximal convoluted tubules in IL-6 KO mice. Experimental heart failure only slightly attenuated the expression of CCN1 protein in the kidney of WT mice and had no effect in IL-6 KO mice. Although, blockade of AT1 receptor did not alter CCN1 protein expression in kidneys of WT mice after myocardial infarction, it significantly changed its CCN1 distribution in the renal tubular system.

Formation of an alkyne during degradation of metal–alkylidyne complexes

The compound [(Ot-Bu)3W≡Ct-Bu] (1) (t-Bu = C(CH3)3) decomposes upon contact with water and several organic products are formed, including di-tert-butylacetylene, t-BuC≡Ct-Bu. This process is reminiscent of the degradation of trinuclear metal-alkylidyne complexes in which free carbynes are ejected into solution, couple and form alkynes along with many other products. The reactivity pattern of the resulting t-BuC carbynes that includes extensive hydrogen abstraction, cleavage of alkynes and lack of reactivity towards alkenes is indicative of a quartet (S = 3/2) spin state. A similar spin state was assigned to other RC (R = alkyl) species that were produced by degrading M3-alkylidyne (M = transition metal) complexes in water. t-BuC≡Ct-Bu is also produced during thermal decomposition of solid 1. In 1977 Fischer and co-workers reported a very similar process in which solids of Br(CO)4Cr≡CR(1) and Br(CO)4Cr≡CR(2) were co-thermolyzed to produce R(1)C≡CR(2), R(1)C≡CR(1), and R(2)C≡CR(2). Fischer had considered the involvement of free carbynes in the making of the alkynes but later resorted to other explanations. The current results suggest that his original proposal is indeed valid.

Развитие двигательных нарушений у самцов мышей линии DBA/2J под влиянием повторного опыта агрессии

Changes in the behavior of DBA/2J mice after gaining repeated experience of aggression have been investigated. It was shown that the long-term experience of aggression led to development of hyperactivity estimated as increased motor activity in different tests: open field, elevated plus maze and during testing of reaction to a novelty. Symptoms of attention deficit estimated in the "partition" test as a reduction of the communicativeness and the lack of reaction to unfamiliar partner were noticed. Appearance of a large number of hyperkinesis manifested most often in the form of sudden involuntary head movements (jerks) was observed in the behavior of aggressive males during agonistic interactions. Most of the changes in the behavior of DBA/2J mice differed significantly from previously detected in the behavior of aggressive mice of C57BL/6J and CBA/Lac strains, suggesting a significant contribution of heredity that determines the features of behavioral disorders that occur under the influence of long-term experience of aggression. Similarity of symptomatics of movement disturbances in mice and in humans with some neurological diseases is discussed.

10 The montmorillonite-catalyzed synthesis of RNA dimer

A synthesis has been developed, providing nucleotide dimers comprising natural or unnatural nucleoside residues. A ribonucleoside 5′-phosphorimidazolide is added to a nucleoside adsorbed on montmorillonite at neutral pH with the absence of protecting groups. Approximately, 30% of the imidazolide is converted into each 2′-5′ dimer and 3′-5′ dimer with the rest hydrolyzed to the 5′-monophosphate. Experiments with many combinations have suggested the limits to which this method may be applied, including heterochiral and chimeric syntheses. This greener chemistry has enabled the synthesis of dimers from activated nucleotides themselves, activated nucleotides with nucleosides, and activated nucleotides with nucleotide 5′-monophosphates. Both homo- and heterochiral combinations of reagents have been tried. The montmorillonite-catalyzed oligomerization of 5′-activated nucleotides leads to oligomers up to 50 residues in length (Huang & Ferris, 2007) using the excellent catalyst Volclay®. However, all oligomers must necessarily begin as dimers, so we considered it important to study in detail the formation of these products under prebiotic conditions. Then, a meaningful comparison could be drawn between our syntheses and the formation of long oligomers that is part of our studies of the origins of life. In the synthesis of trimers from these dimers, we looked for alternative synthetic methods via a 5′-phosphate dimer with activated nucleotides as well as 5′-hydroxy nucleotide dimers with the same reactant. The method has shown promise in targeting trimer synthesis and the procedure lends itself to the development of combinatorial libraries. The use of enzymatic hydrolysis has played a crucial role in this work, facilitating product identity across the spectrum of products prepared. The yields of the corresponding homochiral and heterochiral dimers from A and U will require careful modeling of the reactants in their interactions with both the clay and one another to locate the source of the similarities and differences. The lack of reactivity of arabino- and xylo-nucleosides also poses interesting structural, modeling, and origins of life issues. Results with clays that catalyze long oligomer formation only poorly reveal that they too catalyze these dimer syntheses, albeit less well than Volclay.®

Phosphonic Esters and their Application of Protease Control

α-Aminoalkylphosphonate diaryl esters are potent, irreversible, and highly selective site-directed inhibitors of serine proteases. The structure of the phosphonate group resembles the transition state observed during a peptide bond hydrolysis and therefore phosphonates are referred as transition state analogues. They react with the hydroxyl group of the active site serine residue leading to formation of a stable enzyme-inhibitor complex. Moreover, incorporation of a peptidyl chain at the N-terminus as well as an introduction of electron withdrawing or electron donating substituents within the ester ring structure allows for a generation of specific inhibitors that react only with target serine protease. The great advantage of the aminophosphonate diaryl esters over other classes of inhibitors is their stability in aqueous solutions, no toxicity and lack of reactivity with cysteine, threonine, aspartyl and metalloproteinases. The above resulted in their application as convenient tools to study proteases function and activity using in vivo and in vitro assays of different pathological disorders (diabetes, cancer metastasis, pulmonary diseases or hypertension); to determine the cellular localization of the proteinases (activity based probes), to be used in proteomic approach or as the reactive antigens to develop a catalytic function within the antibodies binding site. Herein we present the development of α-aminoalkylphosphonate diaryl esters as inhibitors of several serine proteases including dipeptidyl peptidase IV, cathepsin G, human neutrophil elastase, mast cell chymase and urokinase-type plasminogen activator. We have provided a historical perspective as well as a comprehensive report of the most recent studies in this field.

Human Anti-Aβ IgGs Target Conformational Epitopes on Synthetic Dimer Assemblies and the AD Brain-Derived Peptide

Soluble non-fibrillar assemblies of amyloid-beta (Aβ) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer’s disease (AD). Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ’s conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody’s nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody’s lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted.

Fabrication and performances of all solid-state symmetric sodium battery based on NASICON-related compounds

The electrochemical performance of a novel all solid-state sodium-ion symmetrical battery with Na3Zr2Si2PO12 (NASICON) as a solid electrolyte and Na3V2(PO4)3 (NVP) as the active electrode material was examined. The all solid-state cell was fabricated by a combination of screen printing and hot pressing. The electrochemical characterization of the NVP active material in the metallic sodium half-cells at 80°C indicated that this NASICON-related phosphate undergoes reversible sodium extraction/insertion reactions at electrode potentials of 1.6 and 3.4V vs. Na. These insertion properties allowed the NVP to function successfully as the active material for both the positive and negative electrodes in a sodium-ion cell configuration. A charge–discharge cycling test of the fabricated symmetrical all solid-state cell was carried out at room temperature within the voltage range of 0.01 and 1.9V. It was found that the cell can work as a secondary battery and showed first discharge capacities of 68 and 32mAhg−1 at the current densities of 1.2 and 10μAcm−2, respectively. Furthermore, the lack of reactivity between the all-solid-state cell components during long-term cycling was confirmed.

Selectivity and Mechanisms Driven by Reaction Dynamics: The Case of the Gas-Phase OH– + CH3ONO2 Reaction

Well-established statistical approaches such as transition-state theory based on high-level calculated potential energy profiles are unable to account for the selectivity observed in the gas-phase OH(-) + CH(3)ONO(2) reaction. This reaction can undergo bimolecular nucleophilic displacement at either the carbon center (S(N)2@C) or the nitrogen center (S(N)2@N) as well as a proton abstraction followed by dissociation (E(CO)2) pathway. Direct dynamics simulations yield an S(N)2:E(CO)2 product ratio in close agreement with experiment and show that the lack of reactivity at the nitrogen atom is due to the highly negative electrostatic potential generated by the oxygen atoms in the ONO(2) group that scatters the incoming OH(-). In addition to these dynamical effects, the nonstatistical behavior of these reactions is attributed to the absence of equilibrated reactant complexes and to the large number of recrossings, which might be present in several ion-molecule gas-phase reactions.

Magnesium analogues of aluminosilicate inorganic polymers (geopolymers) from magnesium minerals

Attempts to synthesise magnesium-containing analogues of aluminosilicate geopolymers from the 1:1 and 2:1 layer magnesiosilicate minerals chrysotile and talc, as well as the magnesium mineral sepiolite are reported. The effect of pre-treating these starting minerals by grinding and/or dehydroxylation was also investigated by XRD, 29Si and natural-abundance 25Mg solid-state magic angle spinning (MAS) NMR spectroscopy. The products from sepiolite most closely resembled an aluminosilicate geopolymer, setting at 40 °C to an X-ray amorphous product containing a broad characteristic 29Si MAS NMR resonance at −90 ppm. The 25Mg MAS NMR spectrum of this product also showed evidence that some of the Mg was located in tetrahedral sites, as expected for a conventional geopolymer. A similar 25Mg MAS NMR result was obtained for chrysotile, but talc proved to be extremely resistant to geopolymer synthesis, requiring treatment at 120 °C for 3 days to set to a friable material retaining the XRD and NMR characteristics of the original talc or its crystalline dehydroxylation products. This lack of reactivity may be related to the 2:1 layer-lattice talc structure, or to the fact that a suitably reactive amorphous product is not formed upon dehydroxylation.

Palladium-Catalyzed Allylic Fluorination of Cinnamyl Phosphorothioate Esters

A highly regioselective, Pd-catalyzed allylic fluorination of phosphorothioate esters is reported. This chemistry addresses several limitations of previously reported methods in which elimination and lack of reactivity were problematic. Preliminary mechanistic investigations reveal that these reactions are stereospecific and provide fluorinated products with net retention of stereochemical configuration. In analogy to other Pd-catalyzed allylic substitution reactions, this process likely proceeds through a palladium π-allyl intermediate.

The bovine CD1D gene has an unusual gene structure and is expressed but cannot present α-galactosylceramide with a C26 fatty acid

Although CD1d and NKT cells have been proposed to have highly conserved functions in mammals, data on functions of CD1d and NKT cells in species other than humans and rodents are lacking. Upon stimulation with the CD1d-presented synthetic antigen α-galactosylceramide, human and rodent type I invariant NKT cells release large amounts of cytokines. The two bovine CD1D (boCD1D) genes have structural features that suggest that they cannot be translated into functional proteins expressed on the cell surface. Here we provide evidence that despite an intron-exon structure and signal peptide that are different from all other known CD1 genes, boCD1D can be translated into a protein that is expressed on the cell surface. However, in vivo treatment of cattle (Bos taurus) with 0.1, 1, or 10 µg kg⁻¹ of the most commonly used α-galactosylceramide, which has a C26 fatty acid, did not lead to an increase in body temperature and serum cytokine levels of the animals. This lack of reactivity is not due to a complete inability of boCD1d to present glycosphingolipids because α-galactosylceramide variants with shorter fatty acids could be presented by boCD1d to human NKT cells in vitro. This suggests that the natural ligands of boCD1d are smaller lipids.

Fibrillary glomerulonephritis complicated by membranous nephropathy in a patient with tuberculosis

Fibrillary glomerulonephritis (FGN) is a morphologically defined entity characterized by glomerular accumulations of non-branching, randomly arranged fibrils; these differ from amyloid fibrils by their larger size and lack of reactivity with Congo red and other amyloid-specific dyes. FGN is a rare disease and may mimic membranous nephropathy under routine light microscopy and immunohistochemistry. However, electron microscopy shows the fibrillary nature of these glomerular deposits. We report a rare case of membranous nephropathy complicated by fibrillary deposits in a 60-year-old man with a history of bone tuberculosis.

1,2‐Oxazine N‐Oxides as Catalyst Resting States in Michael Additions of Aldehydes to Nitro Olefins Organocatalyzed by α,α‐Diphenylprolinol Trimethylsilyl Ether

AbstractBy combining enamines, derived from aldehydes and diphenylprolinol trimethylsilyl ether (the Hayashi catalyst), with nitroethenes ((D6)benzene, 4‐Å molecular sieves, room temperature) intermediates of the corresponding catalytic Michael‐addition cycles were formed and characterized (IR, NMR, X‐ray analysis; Schemes 3–6 and Fig. 1–3). Besides cyclobutanes 2, 1,2‐oxazine N‐oxide derivatives 3–6 and 8 have been identified for the first time, some of which are very stable compounds. It may not be a lack of reactivity (between the intermediate enamines and nitro olefins) that leads to failure of the catalytic reactions (Schemes 3–5) but the high stability of catalyst resting states. The central role zwitterions play in these processes is discussed (Schemes 1 and 2).

ChemInform Abstract: Selective Alkylation of (Hetero)Aromatic Amines with Alcohols Catalyzed by a Ruthenium Pincer Complex.

AbstractThe lack of reactivity concerning aliphatic amines prevents polyalkylation, i.e.

Mammary invasive micropapillary carcinoma in a male cat: Immunohistochemical description and clinical follow-up

We describe the case of a 14-year-old Domestic Short Hair male cat that presented with a single mammary tumour one centimetre in diameter, classified as invasive micropapillary carcinoma. Histology and immunohistochemistry revealed a high mitotic index, a KI-67 index of 10%, a lack of reactivity to myoepithelial markers, and a dense infiltration with T and B lymphocytes at the periphery of the tumour. Micrometastases were detected in the regional lymph node at the time of surgery. Overall survival time was 10 months with a disease-free interval of 7.5 months. Distant metastases in the sublumbar lymph nodes confirmed the aggressiveness of this tumour, which has recently been subtyped in female cats. This is the first case reported in male cats with a complete follow-up, highlighting the importance of prompt and aggressive treatment in the presence of mammary tumours in male cats.

Primary oligodendrocyte death does not elicit anti-CNS immunity

Anti-myelin immunity is commonly thought to drive multiple sclerosis, yet the initial trigger of this autoreactivity remains elusive. One of the proposed factors for initiating this disease is the primary death of oligodendrocytes. To specifically test such oligodendrocyte death as a trigger for anti-CNS immunity, we inducibly killed oligodendrocytes in an in vivo mouse model. Strong microglia-macrophage activation followed oligodendrocyte death, and myelin components in draining lymph nodes made CNS antigens available to lymphocytes. However, even conditions favoring autoimmunity-bystander activation, removal of regulatory T cells, presence of myelin-reactive T cells and application of demyelinating antibodies-did not result in the development of CNS inflammation after oligodendrocyte death. In addition, this lack of reactivity was not mediated by enhanced myelin-specific tolerance. Thus, in contrast with previously reported impairments of oligodendrocyte physiology, diffuse oligodendrocyte death alone or in conjunction with immune activation does not trigger anti-CNS immunity.

Specificity and sensitivity of INI-1 labeling in epithelioid sarcoma. Loss of INI1 expression as a frequent immunohistochemical event in synovial sarcoma Loss of INI1 expression as a frequent immunohistochemical event in synovial sarcoma

INI1 antigen is a product of the INI-1/SMARCB1 gene localized on chromosome 22q. It is well known that INI1 gene inactivation or loss of INI1 antigen expression is observed in epithelioid sarcomas; however, there are only few reports concerning specificity and sensitivity of immunohistochemical INI1 labeling as a marker of this neoplasm. That is why we decided to test 99 soft tissue sarcomas for the presence of the INI1 gene product. More specifically, the analyzed group consisted of 33 synovial sarcomas, 14 fibrosarcomas, 8 desmoid tumors, 8 DFSPs, 5 MPNSTs, 9 epithelioid sarcomas, 11 Ewing sarcomas/PNETs, 9 rhabdomyosarcomas and 2 clear cell sarcomas. Additionally, 7 malignant melanomas and 9 adenocarcinomas were included into the study. Positive staining with an antibody against the INI-1 gene product was observed in all studied cases of MPNST, Ewing sarcoma/PNET, rhabdomyosarcoma, malignant melanoma, clear cell sarcoma, and adenocarcinoma. On the contrary, none of 9 epithelioid sarcomas was labeled. The loss of INI1 expression was also detected in 7 (21.2%) synovial sarcomas, confirmed cytogenetically or by FISH. Considering the lack of reaction with INI-1 antibody as a diagnostic test for epithelioid sarcoma we estimated that its sensitivity reached 100% and specificity - 83.5% (p < 0.0001).