Amine Fragment Research Articles

New flavonoid – N,N-dibenzyl(N-methyl)amine hybrids: Multi-target-directed agents for Alzheimer´s disease endowed with neurogenic properties

The design of multi-target directed ligands (MTDLs) is a valid approach for obtaining effective drugs for complex pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxic cascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking two privileged scaffolds with well-known activities in ND-targets, the flavonoid and the N,N-dibenzyl(N-methyl)amine (DBMA) fragments, new CNS-permeable flavonoid – DBMA hybrids (1–13) were obtained. They were subjected to biological evaluation in a battery of targets involved in Alzheimer’s disease (AD) and other NDs, namely human cholinesterases (hAChE/hBuChE), β-secretase (hBACE-1), monoamine oxidases (hMAO-A/B), lipoxygenase-5 (hLOX-5) and sigma receptors (σ1R/σ2R). After a funnel-type screening, 6,7-dimethoxychromone – DBMA (6) was highlighted due to its neurogenic properties and an interesting MTD-profile in hAChE, hLOX-5, hBACE-1 and σ1R. Molecular dynamic simulations showed the most relevant drug-protein interactions of hybrid 6, which could synergistically contribute to neuronal regeneration and block neurodegeneration.

Anion Recognition Via polarized –N-H Fragments

Hydrogen bonding interaction and or proton transfer assets of synthetic molecules in presence of anionic species is pretty fascinating in the field of supramolecular analytical chemistry. Not only amide or urea based derivatives have appeared in the highlights, rather from last few decades, polarized free amine fragments (-NH2) have been brought under the study with prompt signaling. In this report, I will be focusing on the basic aspects which trigger free amine group to decode rapid anion recognition not only under organic media, but also under aqueous conditions in diverse environments.

The impacts of regional shipping emissions on the chemical characteristics of coastal submicron aerosols near Houston, TX

Abstract. The air quality of the Texas Gulf Coast region historically has been influenced heavily by regional shipping emissions. However, the effects of the recently established North American Emissions Control Area on aerosol concentrations and properties in this region are presently unknown. In order to better understand the current sources and processing mechanisms influencing coastal aerosol near Houston, a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was deployed for 3 weeks at a coastal location during May–June 2016. Total mass loadings of organic and inorganic non-refractory aerosol components during onshore flow periods were similar to those published before establishment of the regulations. Based on estimated methanesulfonic acid (MSA) mass loadings and published biogenic MSA / non-sea-salt sulfate (nss-SO4) ratios, an average of over 75 % of the observed nss-SO4 was from anthropogenic sources, predominantly shipping emissions. Mass spectral analysis indicated that for periods with similar backward-trajectory-averaged meteorological conditions, air masses influenced by shipping emissions had an increased mass fraction of ions related to carboxylic acids and larger oxygen-to-carbon ratios than those that avoided shipping lanes, suggesting that shipping emissions increase marine organic aerosol (OA) oxidation state. Amine fragment mass loadings were correlated positively with anthropogenic nss-SO4 during onshore flow, implying anthropogenic–biogenic interaction in marine OA production. Model calculations also suggest that advection of shipping-derived aerosol may enhance inland aqueous-phase secondary OA production. These results imply a continuing role of shipping emissions on aerosol properties over the Gulf of Mexico and suggest that further regulation of shipping fuel sulfur content will reduce coastal submicron aerosol mass loadings near Houston.

Organic Aerosol Particle Chemical Properties Associated With Residential Burning and Fog in Wintertime San Joaquin Valley (Fresno) and With Vehicle and Firework Emissions in Summertime South Coast Air Basin (Fontana)

AbstractOrganic aerosol mass (OM) components were investigated at Fresno in winter and at Fontana in summer by positive matrix factorization of high‐resolution time‐of‐flight aerosol mass spectra and of Fourier Transform infrared spectra, as well as by k‐means clustering of light‐scattering (LS) aerosol single‐particle spectra. The results were comparable for all three methods at both sites, showing different contributions of primary and secondary organic aerosol sources to PM1. At Fresno biomass burning organic aerosol contributed 27% of OM on low‐fog days, and nitrate‐related oxidized OA (NOOA) accounted for 47% of OM on high‐fog days, whereas at Fontana very oxygenated organic aerosol (VOOA) components contributed 58–69% of OM. Amine and organosulfate fragment concentrations were between 2 and 3 times higher on high‐fog days than on low‐fog days at Fresno, indicating increased formation from fog‐related processes. NOOA and biomass burning organic aerosol components were largely on different particles than the VOOA components in Fresno, but in Fontana both NOOA and VOOA components were distributed on most particle types, consistent with a longer time for and a larger contribution from gas‐phase photochemical secondary organic aerosol formation in summer Fontana than winter Fresno. Uncommon trace organic fragments, elevated inorganic, and alcohol group submicron mass concentrations persisted at Fontana for more than 5 days after 4 July fireworks. These unique aerosol chemical compositions at Fresno and Fontana show substantial and extended air‐quality impacts from residential burning and fireworks.

Coumarin based fluorescent dye for monitoring of siliceous structures in living organisms

Fluorescence dyes capable to specific interactions with definite substances are applied in biology for visualization of organelles and tracking of single molecules. The dyes which bear basic moieties are capable to stain acidic vesicles, including lysosomes and silica deposition vesicles in diatom algae. A new coumarin based fluorescent dye Q-N2 which contains amine fragment was synthesized. The new dye shows blue fluorescence which spectrum in water solutions does not depend on pH value but a green fluorescence appears when the dye is aggregated with siliceous surfaces or is entrapped into siliceous materials, e.g. valves of diatom algae. This effect allows to use Q-N2 dye for tracking silicification and biosilicification processes. Cultivation of diatom algae Ulnaria ferefusiformis (M.Kulikovskiy & H.Lange-Bertalot, 2016) in the presence of Q-N2 shows presence of condensed siliceous particles in the cell cytoplasm in several seconds after beginning of silicic acid consumption from the environment. This observation affords a basis to suppose formation of condensed siliceous structures (oligosilicates) during transportation of silicic acid through the cell membrane.

A short and efficient total synthesis of the bromotyrosine-derived alkaloid psammaplysene A.

Psammaplysene A, an inhibitor of FOXO1a-mediated nuclear export, has been synthesized by a concise and improved route from tyrosine-derived acid and amine fragments which were easily constructed using commercially available p-hydroxybenzaldehyde and tyramine as starting material, respectively. The strategy provides an efficient access of psammaplysene analogues that can be explored for potential pharmaceutical or biological activities.

In vitro and in vivo antiproliferative activity of organo-nickel SCS-pincer complexes on estrogen responsive MCF7 and MC4L2 breast cancer cells. Effects of amine fragment substitutions on BSA binding and cytotoxicity.

A family of organonickel complexes has been prepared, fully characterized, and tested for their antiproliferative activity against estrogen-responsive human breast cancer cells (MCF7). The three SCS-type pincer ligands HL1, HL2, and HL3 and their corresponding Ni(ii) complexes NiL1, NiL2, and NiL3 have been synthesized and fully characterized, including by single crystal diffraction studies for the complexes. The complexes possess square planar geometry with two symmetrical 5-membered nickellacycles. Fluorescence spectroscopy, circular dichroism measurements, molecular modeling, colorimetric based assay and tumor transplantation studies were used to evaluate the protein binding and antiproliferative activities of these organometallic complexes both in vitro and in vivo. Fluorescence quenching was used to investigate bovine serum albumin (BSA) interaction at different temperatures (293, 303 and 313 K), and the results were analyzed using the classical Stern-Volmer equation, allowing us to propose a dynamic quenching mechanism. Studies in vitro on the antiproliferative activity of the three organonickel complexes against estrogen-responsive human breast cancer cells (MCF7) showed promising antitumor activity for NiL1 containing pyrrolidine fragments. In vivo administration of this compound significantly inhibits tumor growth in estrogen-dependent MC4L2 cancer cells in female BALB/c mice.

Copper, cobalt, and nickel complexes of azomethine compounds containing phenylazo group in the amine fragment: Syntheses, structures, and magnetic properties

The Cu, Ni, and Со complexes based on the following new azomethine compounds containing azobenzene groups in the ortho- or para-positions of the amine fragment are synthesized: 2-allyl-6-[(E)-[4-(E)-phenylazophenyl]iminomethyl]phenol (HL1), 2-allyl-6-[(E)-[4-methyl-2-[(E)-phenylazo]-p-tolylazo] iminomethyl]phenol (HL2), 5-methoxy-2-[(E)-[4-[(E)-phenylazo]phenyl]iminoethyl]phenol (HL3), and 5-methoxy-2-[(E)-[4-methyl-2-[(E)-p-tolylazo]phenyl]iminomethyl]phenol (HL4). The structures of the complexes are determined by the data of IR and 1Н NMR spectroscopy (for the azomethine compounds), X-ray absorption spectroscopy, and magnetochemistry. The coordination centers of all Cu complexes have a distorted square structure. A direct dependence of the geometry of the coordination polyhedron on the position of azobenzene groups in the amine fragments of the ligands is found for the Ni and Co complexes. The octahedral environment of the nickel and cobalt ions takes place in the case of the ortho-position of the amine fragment, whereas the square environment for the Ni complexes or the tetrahedral environment for the Co complexes is observed at the para-position. The molecular structures of two azomethines HL1 and HL4 are determined by X-ray diffraction analysis (CIF files CCDC nos. 1552836 (HL1) and 1552837 (HL4)).

Solvation Structure of Surface-Supported Amine Fragments: A Molecular Dynamics Study

Amine-grafted silica gel is an efficient heterogeneous catalyst for the Knoevenagel condensation and draws much attention in green chemistry for applications like heavy metal adsorption and CO2 fixation. Despite its successful usage in diverse areas, fundamental questions remain on how the silica substrate affects the local chemical environment of the tethered amines. In this work, we use all-atom molecular dynamics simulation to investigate the solvation structures of two primary amines tethered onto a silica surface at different pHs of aqueous solutions. The atomic density profiles in the solvation shell are analyzed with a spherical harmonics expansion method for both isolated and silica-supported amines in different aqueous environments. The simulation results provide direct evidence for the strong influence of the silica surface on the hydration structure that is often ignored in the theoretical analysis of surface reactions. The surface effect becomes less prominent on the tethered amine as the alky...

Unusual visible-light photolytic cleavage of tertiary amides during the synthesis of cyclolignans related to podophyllotoxin

During the attempted photochemical cyclization of 2,3-bisbenzylidene-γ-hydroxybutyric acid cyclic amide ester, it was observed that a γ-butyrolactone ring was formed, which was concurrent with the release of the amine fragment from the amide. The process occurs with high yield giving rise to the formation of β-apopicropodophyllin and its regioisomer. Additional experiments confirmed the photochemical nature of this transformation, and that it is independent from the photocyclization of the benzylidene groups – a typical reactivity for the members of the fulgide family. In contrast to the latter UV-driven cyclization, the photochemical cleavage of the amide was proven to proceed under irradiation with visible light.

Palladium(II) complexes bearing di-(2-picolyl)amine functionalized chrysin fragments. An experimental and theoretical study

A new series of chrysin derivatives containing the di-(2-picolyl)amine (2a–d) moiety have been designed, synthesized, and treated with PdCl2·2CH3CN allowing the preparation of new cationic Palladium(II) complexes (3a–d). Solution-phase studies by 1H NMR spectroscopy of 3a–d revealed that the protons of the methylene groups of the di(2-picolyl)amine fragment are diasterotopic. GIAO/DFT studies were performed to predict the molecular structures of 3a–d by comparing the experimental and theoretical 1H-NMR chemical shifts. The molecular structure of 3c was determined by X-ray crystallographic analysis revealing that di-(2-picolyl)amine fragment is coordinated to the palladium center in a κ3-N,N,N-tridentate fashion in an overall square-planar geometry completed with a chloride atom.

2-Cyano-2-indolylpropanoic acid as a chiral derivatizing agent for the absolute configuration assignment of secondary alcohols and primary amines by 1H NMR and VCD

A convenient approach for the absolute configuration assignment of secondary alcohols in the (8R,1′R,2′S,5′R)-15,25, (8S,1′R,2′S,5′R)-15,25, (8R,1′R)-21–24, and (8S,1′R)-21–24 ester series, and of primary amines in the (8R,1′R)-32–37 and (8S,1′R)-32–37 amide series, by means of 1H NMR and VCD spectroscopy, using 2-cyano-2-indolylpropanoic acid as a chiral derivatizing agent is presented. DFT calculations were carried out to demonstrate the anisotropic effect of the indole skeleton on the chiral alcohol or the amine fragment. Vibrational circular dichroism (VCD) measurements of the above series indicated a VCD bisignated couplet resulting from the interaction of the ester carbonyl group and the CN group. The absolute configuration assignments were further tested by X-ray diffraction analysis.

A Modular Strategy for the Direct Catalytic Asymmetric α-Amination of Carbonyl Compounds

Summary Direct catalytic methods for the stereoselective introduction of various non-protected amines at the carbon atom adjacent to a carbonyl group remain elusive in synthetic chemistry, even though they offer the most straightforward entry to chiral α-aminocarbonyl compounds. Here, we demonstrate that the in situ activation of hydroxylamines with trichloroacetonitrile enables direct transfer of their amine moieties to the C-3 position of oxindoles with rigorous enantiocontrol under the catalysis of chiral 1,2,3-triazolium salts. This protocol provides a powerful and practical means of accessing optically active 3-aminooxindoles with a wide array of alkyl and aryl substituents on nitrogen. Other carbonyl compounds, such as β-ketoesters and α-cyanoesters, can also be directly transformed into the corresponding α-aminocarbonyls with high enantioselectivity.

Synthesis of 3,5-disubstituted 1,2,4-triazoles containing an amino group

3,5-Disubstituted 1,2,4-triazoles containing linear and cyclic amine fragments have been synthesized by thermal cyclization of N′-(1-iminoalkyl) hydrazides prepared by condensation of imido esters with carboxylic acid hydrazides. The initial imido esters have been synthesized by the Pinner reaction, as well as by reaction of nitriles with methanol in the presence of a catalytic amount of sodium methoxide. A procedure has been developed for the synthesis of 5-substituted 3-(3-nitrophenyl)-1,2,4-triazoles which have been converted to 3-aminophenyl derivatives by reduction with hydrazine hydrate over Raney nickel.

New neurogenic lipoic-based hybrids as innovative Alzheimer's drugs with σ-1 agonism and β-secretase inhibition.

Neurogenic agents emerge as innovative drugs for the treatment of Alzheimer's disease (AD), whose pathological complexity suggests strengthening research in the multi-target directed ligands strategy. By combining the lipoic acid structure with N-benzylpiperidine or N,N-dibenzyl(N-methyl)amine fragments, new multi-target directed ligands were obtained that act at three relevant targets in AD: σ-1 receptor (σ1R), β-secretase-1 (BACE1) and acetylcholinesterase (AChE). Moreover, they show potent neurogenic properties, good antioxidant capacity and favorable CNS permeability. Molecular modeling studies on AChE, σ1R and BACE1 highlight relevant drug-protein interactions that may contribute to the development of new disease-modifying drugs. New lipoic-based σ1 agonists endowed with neurogenic, antioxidant, cholinergic and amyloid β-peptide-reducing properties have been discovered for the potential treatment of AD.

Effect of azodicarbonamide on microstructure, cure kinetics and physical properties of natural rubber foam

The effect of azodicarbonamide as chemical blowing agent on the morphology, cure kinetics and physical properties of natural rubber foam is investigated. From the morphology, when the amount of chemical blowing agent increases from 3 to 4 phr, the bubble size in the rubber matrix slightly decreases due to the increase of vulcanization reaction rate from the presence of amine fragment species as by-products from the decomposition of azodicarbonamide. The coalescence between bubbles is observed in the specimen with 5 and 6 phr of azodicarbonamide owing to high gas content in the rubber matrix. Moreover, the scorch time slightly reduces and cure rate increases as a function of azodicarbonamide content. The autocatalytic model can be used to explain the curing reaction and mechanism of this natural rubber foam. Furthermore, the activation energy (Ea) directly relates to the bubble size and microvoid structure of natural rubber foam. When compared with the vulcanized natural rubber without adding chemical blowing agent, it is found that the bulk density of natural rubber foam significantly decreases and the volumetric expansion ratio of natural rubber foam increases at high content of chemical blowing agent. Moreover, natural rubber foam at 4 phr of azodicarbonamide exhibits the lowest thermal expansion coefficient due to the smallest bubble size with less coalescence.

New cinnamic – N-benzylpiperidine and cinnamic – N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties

Here we describe new families of multi-target directed ligands obtained by linking antioxidant cinnamic-related structures with N-benzylpiperidine (NBP) or N,N-dibenzyl(N-methyl)amine (DBMA) fragments. Resulting hybrids, in addition to their antioxidant and neuroprotective properties against mitochondrial oxidative stress, are active at relevant molecular targets in Alzheimer’s disease, such as cholinesterases (hAChE and hBuChE) and monoamine oxidases (hMAO-A and hMAO-B). Hybrids derived from umbellic – NBP (8), caffeic – NBP (9), and ferulic – DBMA (12) displayed balanced biological profiles, with IC50s in the low-micromolar and submicromolar range for hChEs and hMAOs, and an antioxidant potency comparable to vitamin E. Moreover, the caffeic – NBP hybrid 9 is able to improve the differentiation of adult SGZ-derived neural stem cells into a neuronal phenotype in vitro.

Tandem high-resolution electrospray ionization mass spectrometry of fluorinated thevinols and 18,19-dihydrothevinols

Fragmentation of fluorinated 18,19-dihydrothevinols and thevinols under electrospray ionization with collisionally activated dissociation accompanied by the elimination of an amine fragment from the cycle and the subsequent loss of H2O and CH3OH have been studied. For thevinol derivatives with a double bond at C18=C19, the [M + H]+ ions undergo the retro-Diels–Alder fragmentation, the abundance of which depends on substituents at the nitrogen and C20 atoms. The retro-Diels–Alder fragmentation of the [M + H]+ ions of thevinols bearing–CH3,–CH2CH=CH2, and $$ - C{H_2} - \triangleleft $$ groups at the nitrogen atom occurs due to the formation of a protonated diene molecule, whereas the elimination of a neutral diene in thevinols with hydrogen at the nitrogen atom has been observed.

Enhancement of the gas barrier property of polypropylene by introducing plasma-treated silane coating with SiOx-modified top-surface

Abstract Polypropylene (PP) is a widely used packaging polymer due to its high transparency and high thermal durability. It is, however, also known to possess a relatively low gas barrier property. To solve the gas barrier problem of PP, a surface modification method by a silane coating was introduced: 3-aminopropyltrimethoxysilane (APTMS) was coated onto PP substrate (APTMS/PP) and treated by oxygen plasma. It was found that, after 60 s of the oxygen plasma treatment, the oxygen transmission rate (OTR) of the APTMS/PP was reduced by a factor of 15 as compared with that of pure PP. The free volume size analyzed by the monoenergetic positron beam significantly decreased at the surface of APTMS observed through the plasma-treatment time. The results indicated that the amount of the free volume of APTMS, through which the gas molecules permeated, was significantly decreased, eventually causing a considerable reduction in the OTR of the APTMS/PP. From the X-ray photoelectron spectroscopy (XPS), it was found that the plasma treatment of APTMS notably reduced both the carbon and the nitrogen atom fractions, simultaneously generating additional Si–O bonding to generate SiOx-like structures at the surface. The formation of the SiOx-like structure at the top surface of the APTMS/PP was considered as the major reason for the enhancement of the oxygen barrier property. In fact, the drastic decrease in the OTR was actually observed at a certain ratio of C/Si. The time of flight secondary ion mass spectroscopy (ToF-SIMS) also revealed that the side-chain scission from the APTMS molecules could generate amine and amide fragments, which could hinder the polymerization of the SiOx. Thus the removal of the fragments would promote the efficient formation of SiOx networks at the top surface of APTMS. Additional plasma treatment could introduce more polymerized SiOx networks in APTMS, resulting in the smaller size of the free volume and hence the higher gas barrier property of APTMS/PP.

Chemical and electrochemical synthesis, local atomic structure, and properties of copper(II), cobalt(II), and nickel(II) complexes with azo compounds containing an additional azo group in the para or ortho position of the amine fragment

New copper(II), cobalt(II), and nickel(II) complexes with 1-[4-(phenydiazenyl)phenyldiazenyl]-naphthalen-2-ol and 1-[4-methyl-2-(4-methylphenyldiazenyl)phenyldiazenyl]naphthalen-2-ol have been synthesized by chemical and electrochemical methods and characterized by IR, 1H NMR, and X-ray absorption spectroscopy, as well as by magnetochemistry and quantum chemical calculations. Coordination of the nitrogen atom in the additional azo group to the metal ion is determined by its position (ortho or para) and metal nature.