Enzymic aromatization of 6-alkyl-substituted androgens, potent competitive and mechanism-based inhibitors of aromatase.

PubMed Central

Numazawa, M; Yoshimura, A; Oshibe, M

1998-01-01

To gain insight into the relationships between the aromatase inhibitory activity of 6-alkyl-substituted androgens, potent competitive inhibitors, and their ability to serve as a substrate of aromatase, we studied the aromatization of a series of 6alpha- and 6beta-alkyl (methyl, ethyl, n-propyl, n-pentyl and n-heptyl)-substituted androst-4-ene-3,17-diones (ADs) and their androsta-1,4-diene-3,17-dione (ADD) derivatives with human placental aromatase, by gas chromatography-mass spectrometry. Among the inhibitors examined, ADD and its 6alpha-alkyl derivatives with alkyl functions less than three carbons long, together with 6beta-methyl ADD, are suicide substrates of aromatase. All of the steroids, except for 6beta-n-pentyl ADD and its n-heptyl analogue as well as 6beta-n-heptyl AD, were found to be converted into the corresponding 6-alkyl oestrogens. The 6-methyl steroids were aromatized most efficiently in each series, and the aromatization rate essentially decreased in proportion to the length of the 6-alkyl chains in each series, where the 6alpha-alkyl androgens were more efficient substrates than the corresponding 6beta isomers. The Vmax of 6alpha-methyl ADD was approx. 2.5-fold that of the natural substrate AD and approx. 3-fold that of the parent ADD. On the basis of this, along with the facts that the rates of a mechanism-based inactivation of aromatase by ADD and its 6alpha-methyl derivative are similar, it is implied that alignment of 6alpha-methyl ADD in the active site could favour the pathway leading to oestrogen over the inactivation pathway, compared with that of ADD. The relative apparent Km values for the androgens obtained in this study are different from the relative Ki values obtained previously, indicating that there is a difference between the ability to serve as an inhibitor and the ability to serve as a substrate in the 6-alkyl androgen series. PMID:9405288

Direct N-alkylation of unprotected amino acids with alcohols

PubMed Central

Yan, Tao; Feringa, Ben L.; Barta, Katalin

2017-01-01

N-alkyl amino acids find widespread application as highly valuable, renewable building blocks. However, traditional synthesis methodologies to obtain these suffer from serious limitations, providing a major challenge to develop sustainable alternatives. We report the first powerful catalytic strategy for the direct N-alkylation of unprotected α-amino acids with alcohols. This method is highly selective, produces water as the only side product leading to a simple purification procedure, and a variety of α-amino acids are mono- or di-N-alkylated, in most cases with excellent retention of optical purity. The hydrophobicity of the products is tunable, and even simple peptides are selectively alkylated. An iron-catalyzed route to mono-N-alkyl amino acids using renewable fatty alcohols is also described that represents an ideal green transformation for obtaining fully bio-based surfactants. PMID:29226249

A Convenient Approach to Synthesizing Peptide C-Terminal N-Alkyl Amides

PubMed Central

Fang, Wei-Jie; Yakovleva, Tatyana; Aldrich, Jane V.

2014-01-01

Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptide C-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the PAL-PEG-PS (Peptide Amide Linker-polyethylene glycol-polystyrene) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides. PMID:22252422

Guanidinylated 3-gluconamidopropyl methacrylamide-s-3-aminopropyl methacrylamide copolymer as siRNA carriers for inhibiting human telomerase reverse transcriptase expression.

PubMed

Wu, Yang; Ji, Jinkai; Yang, Ran; Zhang, Xiaoqiang; Li, Yuanhui; Pu, Yuepu; Li, Xinsong

2013-01-01

In this report, a series of well-defined glucose- and guanidine-based cationic copolymers as gene carriers were developed to inhibit human telomerase reverse transcriptase (hTERT) gene expression. First of all, guandinylated 3-gluconamidopropyl methacrylamide-s-3-aminopropyl methacrylamide copolymers (guanidinylated GAPMA-s-APMA, abbreviated as GGA) were prepared via aqueous reversible addition--fragmentation chain transfer polymerization (RAFT). Then, three target hTERT siRNA TERT-1, TERT-2 and TERT-3 were designed and combined with GGA copolymers to form siRNA/GGA polyplexes. The polyplexes were examined by dynamic light scattering and agarose gel electrophoresis. The results indicated that GGA copolymers can condense siRNA effectively to form particles with the diameter from 157 nm to 411 nm and zeta potential values in the range from +3.7 to +15.8 mV at various charge ratios (N/P). The MTT assay data of siRNA/GGA polyplexes on human hepatocellular liver carcinoma cells (HepG2) indicated that GGA copolymer had better cell viabilities than polyethylenimine (PEI). Furthermore, the transfection of siRNA/GGA polyplexes was detected by real-time quantitative PCR (RT-qPCR) in HepG2. It was found that siRNA/GGA polyplexes could effectively silence hTERT mRNA expression in serum-free media (p<0.01). In the presence of serum, the hTERT mRNA expression in HepG2 cells have significant difference (p<0.01) between siRNA/GGA3 polyplexes and blank. The results showed that the GAPMA component can reduce the aggregation of protein in serum media. Therefore, the enhancement of transfection may be attributed to the combination of guadino groups and glucose component. And, the guandinylated 3-gluconamidopropyl methacrylamide-s-3-aminopropyl methacrylamide copolymers might be promise in gene delivery.

The formation of [M-H]+ ions in N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione derivatives during atmospheric pressure photoionization mass spectrometry.

PubMed

Sioud, Salim; Kharbatia, Najeh; Amad, Maan H; Zhu, Zhiyong; Cabanetos, Clement; Lesimple, Alain; Beaujuge, Pierre

2014-11-30

The formation of ions during atmospheric pressure photoionization (APPI) mass spectrometry in the positive mode usually provides radical cations and/or protonated species. Intriguingly, during the analysis of some N-alkyl-substituted thieno[3,4-c]pyrrole-4,6-dione (TPD) derivatives synthesized in our laboratory, unusual [M-H](+) ion peaks were observed. In this work we investigate the formation of [M-H](+) ions observed under APPI conditions. Multiple experimental parameters, including the type of ionization source, the composition of the solvent, the type of dopant, the infusion flow rate, and the length of the alkyl side chain were investigated to determine their effects on the formation of [M-H](+) ions. In addition, a comparison study of the gas-phase tandem mass spectrometric (MS/MS) fragmentation of [M + H](+) vs [M-H](+) ions and computational approaches were used. [M-H](+) ions were observed under APPI conditions. The type of dopant and the length of the alkyl chain affected the formation of these ions. MS/MS fragmentation of [M-H](+) and [M + H](+) ions exhibited completely different patterns. Theoretical calculations revealed that the loss of hydrogen molecules from the [M + H](+) ions is the most favourable condition under which to form [M-H](+) ions. [M-H](+) ions were detected in all the TPD derivatives studied here under the special experimental conditions during APPI, using a halogenated benzene dopant, and TPD containing substituted N-alkyl side chains with a minimum of four carbon atoms. Density functional theory calculations showed that for [M-H](+) ions to be formed under these conditions, the loss of hydrogen molecules from the [M + H](+)  ions is proposed to be necessary. Copyright © 2014 John Wiley & Sons, Ltd.

40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...

40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...

Reevaluation of the effect of ellagic acid on N-methyl-N-nitrosourea DNA alkylation and mutagenicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lord, H.L.; Josephy, P.D.; Snieckus, V.A.

N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N{sup 7}, guanine O{sup 6}, and adenine N{sup 3}. Dixit and Gold ((1986) Proc. Natl, Acad. Sci. U.S.A. 83, 8039-8043) reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU in Salmonella typhimurium strain TA 100, inhibited salmon sperm DNA alkylation by ({sup 3}H)MNU, and also greatly reduced the ratio of guanine O{sup 6} to guanine N{sup 7} alkylation. We have examined the MNU-induced alkylation of calf thymus DNA and evaluated the effect of ellagic acid on this binding. Ellagic acidmore » had only a slight effect on total alkylation and did not alter the ratio of methylation at guanine-O{sup 6} and -N{sup 7} positions. In further experiments, ellagic acid did not significantly inhibit MNU mutagenicity. These findings do not support the potential use of ellagic acid as an inhibitor of biological damage induced by nitrosoureas.« less

Antimicrobial activity of N-alkoxycarbonylmethyl-N-alkyl-piperidinium chlorides.

PubMed

Woźniak, Edyta; Mozrzymas, Anna; Czarny, Anna; Kocieba, Maja; Rózycka-Roszak, Bozenna; Dega-Szafran, Zofia; Dulewicz, Ewa; Petryna, Magdalena

2004-01-01

The aim of the study was to assay antibacterial and antifungal activity of newly synthesised N-alkoxycarbonylmethyl-N-alkyl-piperidinium chlorides. The compounds tested were found to inhibit the growth of some Gram-negative bacteria, Gram-positive strains and some representatives of yeast-type Candida. From microbiological experiments two of the compounds tested, N-dodecyloxycarbonylmethyl-N-methyl-piperidinium chloride (3) and N-dodecyl-N-ethoxycarbonylmethyl-piperidinium chloride (6), emerged as more active than the other compounds. Since the resistance of biofilms to biocides should be noted during the design and testing of new antimicrobial agents therefore, we have analysed antibacterial properties of the most active compounds towards biofilms. Our study focused on strains of Pseudomonas aeruginosa and Staphylococcus aureus that served as main model organisms for the biofilm studies.

Mass spectrometry of analytical derivatives. 1. Cyanide cations in the spectra of N-alkyl-N-perfluoroacyl-α-amino acids and their methyl esters

PubMed Central

Todua, Nino G.; Tretyakov, Kirill V.; Mikaia, Anzor I.

2016-01-01

The central mission for the development of the National Institute of Standards and Technology/National Institutes of Health/Environmental Protection Agency Mass Spectral Library is the acquisition of reference gas chromatography–mass spectrometry data for important compounds and their chemical modification products. The addition of reliable reference data of various derivatives of amino acids to The Library, and the study of their behavior under electron ionization conditions may be useful for their identification, structure elucidation, and a better understanding of the data obtained when the same derivatives are subjected to other ionization methods. N-Alkyl-N-perfluoroacyl derivatives of amino acids readily produce previously unreported alkylnitrilium cations of composition [HC≡N-alkyl]+. Homologous [HC≡N-aryl]+ cations are typical for corresponding N-aryl analogs. The formation of other ions characteristic for these derivatives involves oxygen rearrangement giving rise to ions [CnF2n+1–C≡N+–CnH2n+1] and [CnF2n+1–C≡N+-aryl]. The introduction of an N-benzyl substituent in a molecule favors a process producing benzylidene iminium cations. l-Threonine and l-cysteine derivatives exhibit more fragmentation pathways not typical for other α-amino acids; additionally, the Nω-amino group in l-lysine directs the dissociation process and provides structural information on the substitution at the amino functions in the molecule. PMID:26307698

Ultrasound promoted N-alkylation of pyrrole using potassium superoxide as base in crown ether.

PubMed

Yim, E S; Park, M K; Han, B H

1997-04-01

Ultrasound accelerates the N-alkylation of pyrrole by alkylating reagents using potassium superoxide as base in the presence of 18-crown-6. A much lower yield of N-alkylated pyrrole was realized in the absence of ultrasound. N-alkylating reagents employed for pyrrole are methyl iodide, ethyl bromide, benzyl bromide, as well as acrylonitrile allyl cyanide and methyl acrylate. In an extension of this work, we have found that ultrasound was not necessary for the N-alkylation of indole and alkyl amine, such as diphenyl amine and piperidine with alkyl halides using our reagents. In all cases we observed that the 18-crown-6 catalyzed N-alkylation reaction gives higher yields of N-alkylated products than that without crown ether, when potassium superoxide was used as base. These observations are probably due to the potassium-crown complex which can be released when the reaction goes to completion.

40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

Code of Federal Regulations, 2010 CFR

2010-07-01

... hydrocarbons. 721.840 Section 721.840 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.840 Alkyl substituted diaromatic hydrocarbons. (a) Chemical substance... alkyl substituted di-aro-matic hydrocarbons (PMN P-91-710) is subject to reporting under this section...

40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

Code of Federal Regulations, 2011 CFR

2011-07-01

... hydrocarbons. 721.840 Section 721.840 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.840 Alkyl substituted diaromatic hydrocarbons. (a) Chemical substance... alkyl substituted di-aro-matic hydrocarbons (PMN P-91-710) is subject to reporting under this section...

Thermodynamic Interactions between Polystyrene and Long-Chain Poly(n-Alkyl Acrylates) Derived from Plant Oils.

PubMed

Wang, Shu; Robertson, Megan L

2015-06-10

Vegetable oils and their fatty acids are promising sources for the derivation of polymers. Long-chain poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) are readily derived from fatty acids through conversion of the carboxylic acid end-group to an acrylate or methacrylate group. The resulting polymers contain long alkyl side-chains with around 10-22 carbon atoms. Regardless of the monomer source, the presence of alkyl side-chains in poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) provides a convenient mechanism for tuning their physical properties. The development of structured multicomponent materials, including block copolymers and blends, containing poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) requires knowledge of the thermodynamic interactions governing their self-assembly, typically described by the Flory-Huggins interaction parameter χ. We have investigated the χ parameter between polystyrene and long-chain poly(n-alkyl acrylate) homopolymers and copolymers: specifically we have included poly(stearyl acrylate), poly(lauryl acrylate), and their random copolymers. Lauryl and stearyl acrylate were chosen as model alkyl acrylates derived from vegetable oils and have alkyl side-chain lengths of 12 and 18 carbon atoms, respectively. Polystyrene is included in this study as a model petroleum-sourced polymer, which has wide applicability in commercially relevant multicomponent polymeric materials. Two independent methods were employed to measure the χ parameter: cloud point measurements on binary blends and characterization of the order-disorder transition of triblock copolymers, which were in relatively good agreement with one another. The χ parameter was found to be independent of the alkyl side-chain length (n) for large values of n (i.e., n > 10). This behavior is in stark contrast to the n-dependence of the χ parameter predicted from solubility parameter theory. Our study complements prior work investigating the interactions between

Influence of N-alkylation on organ distribution of radioiodinated amphetamines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Machulla, H.J.; Schmidt, U.; Mehdorn, H.M.

1985-05-01

In spite of numerous animal data and the widespread clinical application of p-(I-123)-N-isopropyl-amphetamine, questions remain open about the role of N-alkylation. Therefore, amphetamine (AP), N-methyl- (MeAP), and N-isopropyl-amphetamine (IsAP) were radioiodinated in the para position and the organ distribution was determined in male mice (Freiburg tribe) 10 weeks of age. In the lungs, all derivatives showed principally the same kinetics. In brain, the maximum uptake was reached after 30 min with 12%/g for AP and MeAP, and 10.5%/g for IsAP. In liver, the radioactivity similarly increased during the first 15 min to approx. 12%/g; afterwards, AP clearly decreased but MeAPmore » remained almost constant up to 120 min and, even more, IsAP increased to a maximum of 18%/g at 30 min. The same brain uptake kinetics for all 3 substances exclude the importance of lipophilicity increased by the N-alkylation. Furthermore, the differences in the liver kinetics of AP and both MeAP and IsAP indicate the importance of liver metabolism on the alkylated amphetamines. The results support the hypothesis that the first important metabolite of the N-alkylated derivatives is the amphetamine which accumulates in the brain as do MeAP and IsAP. On the basis of these findings, AP was applied clinically showing the same efficient brain uptake and distribution in SPECT as IsAP.« less

Cyclopropylamines from N,N-dialkylcarboxamides and Grignard reagents in the presence of titanium tetraisopropoxide or methyltitanium triisopropoxide.

PubMed

de Meijere, Armin; Chaplinski, Vladimir; Winsel, Harald; Kordes, Markus; Stecker, Björn; Gazizova, Vesta; Savchenko, Andrei I; Boese, Roland; Schill, Farina

2010-12-10

Thirty-three different N,N-dialkyl- and N-alkyl-N-phosphorylalkyl-substituted carboxamides 9-17 were treated with unsubstituted as well as with 2-alkyl-, 2,2-dialkyl-, and 3-alkenyl-substituted ethylmagnesium bromides 6 in the presence of stoichiometric amounts of titanium tetraisopropoxide or methyltitanium triisopropoxide to furnish substituted cyclopropylamines 20-25 in 20-98% yield, depending on the substituents with no (1:1) to excellent (>25:1) diastereoselectivities. Generally higher yields (up to 98%) of the cyclopropylamines 20-28 without loss of the diastereoselectivity were obtained with methyltitanium triisopropoxide as the titanium mediator. Under these conditions, even dioxolane-protected ketones and halogen-substituted and chiral as well as achiral alkyloxyalkyl-substituted carboxamides could be converted to the correspondingly substituted cyclopropylamines with unsubstituted as well as phenyl- and a variety of alkyl-substituted ethylmagnesium bromides in addition to numerous heteroatom-containing (e.g., halogen-, trityloxy-, tetrahydropyranyloxy-substituted) Grignard reagents (62 examples altogether). The transformation of N,N-diformylalkylamines 54 with ethylmagnesium bromide in the presence of methyltitanium triisopropoxide to N,N-dicyclopropyl-N-alkylamines 55 can be brought about in up to 82% yield (6 examples). An asymmetric variant of the titanium-mediated cyclopropanation of N,N-dialkylcarboxamides has been developed by applying chiral titanium mediators generated from stoichiometric amounts of titanium tetraisopropoxide and chiral diamino or diol ligands, respectively. The most efficient chiral mediators turned out to be titanium bistaddolates that provided the corresponding cyclopropylamines with enantiomeric excesses (ee) of up to 84%. Evaluation of several silyl-based additives revealed that the reaction can also efficiently be carried out with substoichiometric amounts (down to 25 mol%) of the titanium reagent, as long as 2-aryl- or 2

Extensive reprogramming of the genetic code for genetically encoded synthesis of highly N-alkylated polycyclic peptidomimetics.

PubMed

Kawakami, Takashi; Ishizawa, Takahiro; Murakami, Hiroshi

2013-08-21

Cyclic structures can increase the proteolytic stability and conformational rigidity of peptides, and N-alkylation of the peptide backbone can make peptides more cell-permeable and resistant to proteolysis. Therefore, cyclic N-alkyl amino acids are expected to be useful building blocks to increase simultaneously these pharmacological properties of peptides. In this study, we screened various cyclic N-alkyl amino acids for their ribosomal incorporation into peptides and identified cyclic N-alkyl amino acids that can be efficiently and successively incorporated. We also demonstrated genetic code reprogramming for reassigning 16 NNU codons to 16 different cyclic N-alkyl amino acids with high fidelity to synthesize highly N-alkylated polycyclic peptidomimetics and an mRNA-displayed library of completely N-alkylated polycyclic peptidomimetics by using our recently developed TRAP (transcription/translation coupled with association of puromycin linker) display. In vitro selection from a highly diverse library of such completely N-alkylated polycyclic peptidomimetics could become a powerful means to discover small-molecule ligands such as drug candidates that can be targeted to biomolecules inside living cells.

40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Halogenated-N-(2-propenyl)-N... New Uses for Specific Chemical Substances § 721.275 Halogenated-N-(2-propenyl)-N-(substituted phenyl... identified generically as halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide (P-83-1085) is subject...

40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Halogenated-N-(2-propenyl)-N... New Uses for Specific Chemical Substances § 721.275 Halogenated-N-(2-propenyl)-N-(substituted phenyl... identified generically as halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide (P-83-1085) is subject...

Self-Assembled Hydrogels from Poly[N-(2-hydroxypropyl)methacrylamide] Grafted with β-Sheet Peptides

PubMed Central

Radu-Wu, Larisa C.; Yang, Jiyuan; Wu, Kuangshi; Kopeček, Jindřich

2009-01-01

A new hybrid hydrogel based on poly[N-(2-hydroxypropyl)methacrylamide] grafted with a β-sheet peptide, Beta11, was designed. Circular dichroism spectroscopy indicated that the folding ability of β-sheet peptide was retained in the hybrid system, whereas the sensitivity of the peptide towards temperature and pH variations was hindered. The polymer backbone also prevented the twisting of the fibrils that resulted from the antiparallel arrangement of the β-strands, as proved by Fourier transform infrared spectroscopy. Thioflavin T binding experiments and transmission electron microscopy showed fibril formation with minimal lateral aggregation. As a consequence, the graft copolymer self-assembled into a hydrogel in aqueous environment. This process was mediated by association of β-sheet domains. Scanning electron microscopy revealed a particular morphology of the network, characterized by long-range order and uniformly aligned lamellae. Microrheology results confirmed that concentration-dependent gelation occurred. PMID:19591463

N-alkyl functionalised expanded ring N-heterocyclic carbene complexes of rhodium(I) and iridium(I): structural investigations and preliminary catalytic evaluation.

PubMed

Dunsford, Jay J; Tromp, Dorette S; Cavell, Kingsley J; Elsevier, Cornelis J; Kariuki, Benson M

2013-05-28

A series of new N-alkyl functionalised 6- and 7-membered expanded ring N-heterocyclic carbene (NHC) pro-ligands 3-6 and their corresponding complexes of rhodium(I) and iridium(I), [M(NHC)(COD)Cl] 7-14 and [M(NHC)(CO)2Cl] 15-22 are described. The complexes have been characterised by (1)H and (13)C{(1)H} NMR, mass spectrometry, IR and X-ray diffraction. It is noted from X-ray diffraction studies that the N-alkyl substituents are found to orientate themselves away from the metal centre due to unfavourable steric interactions resulting in low percent buried volume (%V(bur)) values in the solid state. The heterocycle ring size is also found to dictate the spatial orientation of the N-alkyl substituents in the neopentyl functionalised derivatives 10 and 14. The 7-membered derivative 14 allows for a conformational 'twist' of the heterocycle ring with the N-alkyl substituents adopting a mutually trans configuration with respect to each other, while the more rigid 6-membered system 10 does not allow for this conformational 'twist' and consequently the N-alkyl substituents adopt a mutually cis configuration. The σ-donor function of this new class of expanded ring NHC ligand has also been probed by measured IR stretching frequencies of the [M(NHC)(CO)2Cl] complexes 15-22. A preliminary catalytic survey of the hydrogenation of functionalised alkenes with molecular hydrogen under mild conditions has also been undertaken with complex , affording an insight into the application of large ring NHC ancillary ligands bearing N-alkyl substituents in hydrogenation transformations.

40 CFR 721.10711 - Alkyl substituted catechol (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10711 Alkyl substituted catechol (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl...

Effect of the alkyl chain length on the rotational dynamics of nonpolar and dipolar solutes in a series of N-alkyl-N-methylmorpholinium ionic liquids.

PubMed

Khara, Dinesh Chandra; Kumar, Jaini Praveen; Mondal, Navendu; Samanta, Anunay

2013-05-02

Rotational dynamics of two dipolar solutes, 4-aminophthalimide (AP) and 6-propionyl-2-dimethylaminonaphthalene (PRODAN), and a nonpolar solute, anthracene, have been studied in N-alkyl-N-methylmorpholinium (alkyl = ethyl, butyl, hexyl, and octyl) bis(trifluoromethansulfonyl)imide (Tf2N) ionic liquids as a function of temperature and excitation wavelength to probe the microheterogeneous nature of these ionic liquids, which are recently reported to be more structured than the imidazolium ionic liquids (Khara and Samanta, J. Phys. Chem. B2012, 116, 13430-13438). Analysis of the measured rotational time constants of the solutes in terms of the Stokes-Einstein-Debye (SED) hydrodynamic theory reveals that with increase in the alkyl chain length attached to the cationic component of the ionic liquids, AP shows stick to superstick behavior, PRODAN rotation lies between stick and slip boundary conditions, whereas anthracene exhibits slip to sub slip behavior. The contrasting rotational dynamics of these probe molecules is a reflection of their location in distinct environments of the ionic liquids thus demonstrating the heterogeneity of these ionic liquids. The microheterogeneity of these media, in particular, those with the long alkyl chain, is further evidence from the excitation wavelength dependence study of the rotational diffusion of the dipolar probe molecules.

[The biochemical mechanisms of the action of N-alkyl-N-nitrosoureas. The possible reasons for drug resistance to these compounds].

PubMed

Syrkin, A B; Gorbacheva, L B

1996-01-01

N-alkyl-N-nitrosoureas exhibit a wide spectrum of antitumor activity. They react as alkylating agents at nucleophilic sites in purine and pyrimidine moieties of DNA. The predominant site of this alkylation is N7 of guanine, which is followed by the site N3 of adenine and 06 of guanine. The formation and persistence of 0(6)-alkylguanine (0(6)-AG) may be of primary importance in cytotoxicity of the nitrosoureas. 0(6)-AG adducts of DNA of the tumor cells are repaired by protein 0(6)-alkylguanine-DNA transferase (0(6)-AGT) which transfers the alkyl group to internal cysteine residue being the acceptor protein for the alkyl group in an irreversible transfer reaction. 0(6)-AGT can protect the tumor cells against 0(6)-AG adducts by the way of inhibiting the formation of the DNA interstrand cross-links 0(6)-AGT plays an important role in the drug resistance because it repairs the DNA alkyl adducts at the 0(6) position of guanine. The 0(6)-AGT activity inversely correlates with the cytotoxic effect of the nitrosoureas. The agents like 0(6)-methylguanosine, 0(6)-methyl-2'-deoxyguanosine, and some 0(6)-benzylated guanine derivatives are effective inactivators of 0(6)-AGT, and thus can be used to enhance the cytotoxicity of N-nitrosoureas. The activation of 0(6)-AGT and other repairing enzymes such as alpha and beta DNA-polymerases as well as an increase in the level of reduced glutathione may be used in developing the resistance to the nitrosoureas.

40 CFR 721.3812 - Substituted phenols and formaldehyde polymer, alkylated (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... polymer, alkylated (generic). 721.3812 Section 721.3812 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.3812 Substituted phenols and formaldehyde polymer... substance identified generically as substituted phenols and formaldehyde polymer, alkylated (PMN P-00-0542...

40 CFR 721.3812 - Substituted phenols and formaldehyde polymer, alkylated (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... polymer, alkylated (generic). 721.3812 Section 721.3812 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.3812 Substituted phenols and formaldehyde polymer... substance identified generically as substituted phenols and formaldehyde polymer, alkylated (PMN P-00-0542...

40 CFR 721.3812 - Substituted phenols and formaldehyde polymer, alkylated (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... polymer, alkylated (generic). 721.3812 Section 721.3812 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.3812 Substituted phenols and formaldehyde polymer... substance identified generically as substituted phenols and formaldehyde polymer, alkylated (PMN P-00-0542...

40 CFR 721.3812 - Substituted phenols and formaldehyde polymer, alkylated (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... polymer, alkylated (generic). 721.3812 Section 721.3812 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.3812 Substituted phenols and formaldehyde polymer... substance identified generically as substituted phenols and formaldehyde polymer, alkylated (PMN P-00-0542...

40 CFR 721.3812 - Substituted phenols and formaldehyde polymer, alkylated (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... polymer, alkylated (generic). 721.3812 Section 721.3812 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.3812 Substituted phenols and formaldehyde polymer... substance identified generically as substituted phenols and formaldehyde polymer, alkylated (PMN P-00-0542...

40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 2-Chloro-N-methyl-N-substituted... Specific Chemical Substances § 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance 2-chloro-N...

40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 2-Chloro-N-methyl-N-substituted... Specific Chemical Substances § 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance 2-chloro-N...

Tribology of monolayer films: comparison between n-alkanethiols on gold and n-alkyl trichlorosilanes on silicon.

PubMed

Booth, Brandon D; Vilt, Steven G; McCabe, Clare; Jennings, G Kane

2009-09-01

This Article presents a quantitative comparison of the frictional performance for monolayers derived from n-alkanethiolates on gold and n-alkyl trichlorosilanes on silicon. Monolayers were characterized by pin-on-disk tribometry, contact angle analysis, ellipsometry, and electrochemical impedance spectroscopy (EIS). Pin-on-disk microtribometry provided frictional analysis at applied normal loads from 10 to 1000 mN at a speed of 0.1 mm/s. At low loads (10 mN), methyl-terminated n-alkanethiolate self-assembled monolayers (SAMs) exhibited a 3-fold improvement in coefficient of friction over SAMs with hydroxyl- or carboxylic-acid-terminated surfaces. For monolayers prepared from both n-alkanethiols on gold and n-alkyl trichlorosilanes on silicon, a critical chain length of at least eight carbons is required for beneficial tribological performance at an applied load of 9.8 mN. Evidence for disruption of chemisorbed alkanethiolate SAMs with chain lengths n n-octadecyl dimethylchlorosilane and n-octadecyl trichlorosilane withstood normal loads at least 30 times larger than those that damaged octadecanethiolate SAMs. Collectively, our results show that the tribological properties of monolayer films are dependent on their internal stabilities, which are influenced by cohesive chain interactions (van der Waals) and the adsorbate-substrate bond.

Additive In Vitro Antiplasmodial Effect of N-Alkyl and N-Benzyl-1,10-Phenanthroline Derivatives and Cysteine Protease Inhibitor E64

PubMed Central

Wijayanti, Mahardika Agus; Sholikhah, Eti Nurwening; Hadanu, Ruslin; Jumina, Jumina; Supargiyono, Supargiyono; Mustofa, Mustofa

2010-01-01

Potential new targets for antimalarial chemotherapy include parasite proteases, which are required for several cellular functions during the Plasmodium falciparum life cycle. Four new derivatives of N-alkyl and N-benzyl-1,10-phenanthroline have been synthesized. Those are (1)-N-methyl-1,10-phenanthrolinium sulfate, (1)-N-ethyl-1,10-phenanthrolinium sulfate, (1)-N-benzyl-1,10-phenanthrolinium chloride, and (1)-N-benzyl-1,10-phenanthrolinium iodide. Those compounds had potential antiplasmodial activity with IC50 values from 260.42 to 465.38 nM. Cysteine proteinase inhibitor E64 was used to investigate the mechanism of action of N-alkyl and N-benzyl-1,10-phenanthroline derivatives. A modified fixed-ratio isobologram method was used to study the in vitro interactions between the new compounds with either E64 or chloroquine. The interaction between N-alkyl and N-benzyl-1,10-phenanthroline derivatives and E64 was additive as well as their interactions with chloroquine were also additive. Antimalarial mechanism of chloroquine is mainly on the inhibition of hemozoin formation. As the interaction of chloroquine and E64 was additive, the results indicated that these new compounds had a mechanism of action by inhibiting Plasmodium proteases. PMID:22332022

Alkylation of deoxyribonucleic acid by carcinogens dimethyl sulphate, ethyl methanesulphonate, N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea. Relative reactivity of the phosphodiester site thymidylyl(3'-5')thymidine.

PubMed Central

Swenson, D H; Lawley, P D

1978-01-01

1. The ethyl phosphotriester of thymidylyl(3'-5')thymidine, dTp(Et)dT, was identified as a product from reaction of DNA with N-ethyl-N-nitrosourea, by procedures parallel to those reported previously for the methyl homologue produced by N-methyl-N-nitrosourea. 2. Enzymic degradation to yield alkyl phosphotriesters from DNA alkylated by these carcinogens and by dimethyl sulphate and ethyl methanesulphonate was studied quantitatively, and the relative yields of the triesters dTp(Alk)dT were determined. The relative reactivity of the phosphodiester group dTpdT to each of the four carcinogens was thus obtained, and compared with that of DNA overall, or with that of the N-7 atom of guanine in DNA. Relative reactivity of the phosphodiester group was lowest towards dimethyl sulphate, the least electrophilic of the reagents used, and was highest towards N-ethyl-N-nitrosourea, the most electrophilic reagent. 3. The nature of the alkyl group transferred also influenced reactivity of the phosphodiester site, since this site was relatively more reactive towards ethylation than would be predicted simply from the known Swain-Scott s values of the alkylating agents. It was therefore suggested that the steric accessibility of the weakly nucleophilic phosphodiester group on the outside of the DNA macromolecule favours its reaction with ethylating, as opposed to methylating, reagents. 4. Taking a value of the Swain-Scott nucleophilicity (n) of 2.5 for an average DNA nucleotide unit [Walles & Ehrenberg (1969) Acta Chem. Scand. 23, 1080-1084], a value of n of about 1 for the phosphodiester group was deduced, and this value was found to be 2-3 units less than that for the N-7 atom of guanine in DNA. 5. The reactivity of DNA overall was markedly high towards the alkylnitrosoureas, despite their relatively low s values. This was ascribed to an electrostatic factor that favoured reaction of the negatively charged polymer with alkyldiazonium cation intermediates. PMID:208508

Design of a Photoredox Catalyst that Enables the Direct Synthesis of Carbamate-Protected Primary Amines via Photoinduced, Copper-Catalyzed N-Alkylation Reactions of Unactivated Secondary Halides.

PubMed

Ahn, Jun Myun; Peters, Jonas C; Fu, Gregory C

2017-12-13

Despite the long history of S N 2 reactions between nitrogen nucleophiles and alkyl electrophiles, many such substitution reactions remain out of reach. In recent years, efforts to develop transition-metal catalysts to address this deficiency have begun to emerge. In this report, we address the challenge of coupling a carbamate nucleophile with an unactivated secondary alkyl electrophile to generate a substituted carbamate, a process that has not been achieved effectively in the absence of a catalyst; the product carbamates can serve as useful intermediates in organic synthesis as well as bioactive compounds in their own right. Through the design and synthesis of a new copper-based photoredox catalyst, bearing a tridentate carbazolide/bisphosphine ligand, that can be activated upon irradiation by blue-LED lamps, we can achieve the coupling of a range of primary carbamates with unactivated secondary alkyl bromides at room temperature. Our mechanistic observations are consistent with the new copper complex serving its intended role as a photoredox catalyst, working in conjunction with a second copper complex that mediates C-N bond formation in an out-of-cage process.

Ionic liquid containing hydroxamate and N-alkyl sulfamate ions

DOEpatents

Friesen, Cody A.; Wolfe, Derek; Johnson, Paul Bryan

2016-03-15

Embodiments of the invention are related to ionic liquids and more specifically to ionic liquids used in electrochemical metal-air cells in which the ionic liquid includes a cation and an anion selected from hydroxamate and/or N-alkyl sulfamate anions.

Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines.

PubMed

Sakamoto, Ryu; Sakurai, Shunya; Maruoka, Keiji

2017-07-06

The copper-catalyzed selective mono-N-alkylation of primary amides or arylamines using alkylsilyl peroxides as alkylating agents is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the alkylsilyl peroxides, as well as to the primary amides and arylamines. Mechanistic studies suggest that the present reaction should proceed through a free-radical process that includes alkyl radicals generated from the alkylsilyl peroxides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric radical alkylation of N-sulfinimines under visible light photocatalytic conditions.

PubMed

Garrido-Castro, Alberto F; Choubane, Houcine; Daaou, Mortada; Maestro, M Carmen; Alemán, José

2017-07-06

In this communication, a new photocatalytic strategy for the addition of alkyl-radical derivatives to N-sulfinimines with complete diastereoselectivity and moderate to good yields is presented. This is the first asymmetric photocatalytic addition to N-sulfinimines under visible light irradiation with smooth conditions and functional group tolerance.

N1-Alkylated 3,4-dihydropyrimidine-2(1H)-ones: Convenient one-pot selective synthesis and evaluation of their calcium channel blocking activity.

PubMed

Singh, Kamaljit; Arora, Divya; Poremsky, Elizabeth; Lowery, Jazmyne; Moreland, Robert S

2009-05-01

It has been found that selective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones can be achieved under solvent-less, mild phase transfer catalytic (PTC) conditions with tetrabutylammonium hydrogen sulfate and 50% aqueous NaOH as the catalyst and base, respectively. The procedure is tolerant to substitutional variation at key diversity points on the pyrimidinone moiety.

Synthesis of 6-alkyluridines from 6-cyanouridine via zinc(II) chloride-catalyzed nucleophilic substitution with alkyl Grignard reagents.

PubMed

Shih, Yu-Chiao; Yang, Ya-Ying; Lin, Chun-Chi; Chien, Tun-Cheng

2013-04-19

6-Cyanouracil derivatives underwent a direct nucleophilic substitution reaction with alkyl Grignard reagents in the presence of zinc(II) chloride as a catalyst to form the corresponding 6-alkyluracils. This methodology is applicable to sugar-protected 6-cyanouridine and 6-cyano-2'-deoxyuridine without the protection at the N(3)-imide and provides a facile and general access to versatile 6-alkyluracil and 6-alkyluridine derivatives.

40 CFR 721.6540 - Acrylamide, polymers with tetraalkyl ammonium salt and polyalkyl, aminoalkyl meth-a-cryl-a-mide...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Acrylamide, polymers with tetraalkyl... CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6540 Acrylamide, polymers... as acrylamide, polymers with tetraalkyl ammonium salt and poly-al-kyl, amino alkyl meth-a-cryl-a-mide...

40 CFR 721.6540 - Acrylamide, polymers with tetraalkyl ammonium salt and polyalkyl, aminoalkyl meth-a-cryl-a-mide...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Acrylamide, polymers with tetraalkyl... CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6540 Acrylamide, polymers... as acrylamide, polymers with tetraalkyl ammonium salt and poly-al-kyl, amino alkyl meth-a-cryl-a-mide...

40 CFR 721.6540 - Acrylamide, polymers with tetraalkyl ammonium salt and polyalkyl, aminoalkyl meth-a-cryl-a-mide...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Acrylamide, polymers with tetraalkyl... CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6540 Acrylamide, polymers... as acrylamide, polymers with tetraalkyl ammonium salt and poly-al-kyl, amino alkyl meth-a-cryl-a-mide...

40 CFR 721.6540 - Acrylamide, polymers with tetraalkyl ammonium salt and polyalkyl, aminoalkyl meth-a-cryl-a-mide...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Acrylamide, polymers with tetraalkyl... CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6540 Acrylamide, polymers... as acrylamide, polymers with tetraalkyl ammonium salt and poly-al-kyl, amino alkyl meth-a-cryl-a-mide...

40 CFR 721.6540 - Acrylamide, polymers with tetraalkyl ammonium salt and polyalkyl, aminoalkyl meth-a-cryl-a-mide...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Acrylamide, polymers with tetraalkyl... CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6540 Acrylamide, polymers... as acrylamide, polymers with tetraalkyl ammonium salt and poly-al-kyl, amino alkyl meth-a-cryl-a-mide...

Domino Acylation/Diels-Alder Synthesis of N-Alkyl-octahydroisoquinolin-1-one-8-carboxylic Acids under Low-Solvent Conditions.

PubMed

Slauson, Stephen R; Pemberton, Ryan; Ghosh, Partha; Tantillo, Dean J; Aubé, Jeffrey

2015-05-15

The development of the domino reaction between an aminoethyl-substituted diene and maleic anhydride to afford an N-substituted octahydroisoquinolin-1-one is described. A typical procedure involves the treatment of a 1-aminoethyl-substituted butadiene with maleic anhydride at 0 °C to room temperature for 20 min under low-solvent conditions, which affords a series of isoquinolinone carboxylic acids in moderate to excellent yields. NMR monitoring suggested that the reaction proceeded via an initial acylation step followed by an intramolecular Diels-Alder reaction. For the latter step, a significant rate difference was observed depending on whether the amino group was substituted by a phenyl or an alkyl (usually benzyl) substituent, with the former noted by NMR to be substantially slower. The Diels-Alder step was studied by density functional theory (DFT) methods, leading to the conclusion that the degree of preorganization in the starting acylated intermediate had the largest effect on the reaction barriers. In addition, the effect of electronics on the aromatic ring in N-phenyl substrates was studied computationally and experimentally. Overall, this protocol proved considerably more amenable to scale up compared to earlier methods by eliminating the requirement of microwave batch chemistry for this reaction as well as significantly reducing the quantity of solvent.

Retention behavior of alkyl-substituted polycyclic aromatic sulfur heterocycle isomers in gas chromatography on stationary phases of different selectivity.

PubMed

Wilson, Walter B; Sander, Lane C; Oña-Ruales, Jorge O; Mössner, Stephanie G; Sidisky, Leonard M; Lee, Milton L; Wise, Stephen A

2017-02-10

Retention indices for 10 sets of alkyl-substituted polycyclic aromatic sulfur heterocycles (PASHs) isomers (total of 80 PASHs) were determined using gas chromatography with three different stationary phases: a 50% phenyl phase, a 50% liquid crystalline dimethylpolysiloxane (LC-DMPS) phase, and an ionic liquid (IL) phase. Correlations between the retention behavior on the three stationary phases and PASH geometry [length-to-breadth (L/B) and thickness (T)] were investigated for the following PASHs: 4 methyl-substituted dibenzothiophenes (DBTs), 3 ethyl-substituted DBTs, 15 dimethyl-substituted DBTs, 8 trimethyl-substituted DBTs, 15 methyl-substituted naphthothiophenes, 30 methyl-substituted benzonaphthothiophenes, and 5 methyl-substituted tetrapheno[1,12-bcd]thiophene. Correlation coefficients for retention on the 50% phenyl phase vs L/B ranged from r=-0.28 (MeBbN23Ts) to r=0.92 (EtDBTs). Correlation coefficients for retention on the IL phase vs L/B ranged from r=0.13 (MeN12Ts) to r=0.83 (EtDBTs). Correlation coefficients for retention on the 50% LC-DMPS phase vs L/B ranged from r=0.22 (MeDBTs) to r=0.84 (TriMeDBTs). Published by Elsevier B.V.

Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs.

PubMed

Kostić, Nađa; Dotsikas, Yannis; Malenović, Anđelija; Medenica, Mirjana

2013-11-15

In the current study, three antiepileptic drugs with zwitterionic properties, namely vigabatrin, pregabalin and gabapentin, were chosen as model analytes to undergo derivatization by applying various n-alkyl chloroformate/n-alcohol combinations, followed by LC-ESI-MS/MS analysis. The employment of 16 combinations per drug using methyl, ethyl, propyl or butyl chloroformate coupled with methanol, ethanol, propanol or butanol, greatly affected a series of parameters of the derivatives, such as retention time on C8 column, signal expressed via areas, limit of detection values, as well as the yields of the main and side reactions. Practically, even slight modification of n-alkyl group of either chloroformate or alcohol resulted in significant changes in the chromatographic and mass spectrometric behavior of the novel derivative. It was clearly demonstrated that all the estimated parameters were highly correlated with the length of n-alkyl groups of the involved chloroformate and alcohol. The most significant influence was monitored in peak area values, indicating that the length of the n-alkyl chain plays an important role in electrospray ionization efficiency. For this parameter, increasing the n-alkyl chain from methyl to butyl led to increment up to 2089%, 508.7% and 1075% for area values of derivatized vigabatrin, pregabalin and gabapentin, respectively. These changes affected also the corresponding values of limits of detection, with the estimated improvements up to 1553%, 397.7% and 875.0% for the aforementioned derivatized drugs, respectively. Besides the obvious utilization of these conclusions in the development of bioanalytical methods for these analytes with the current protocol, this study offers valuable data which can be useful in more general approaches, giving insights into the effects of this derivatization reaction and its performances. Copyright © 2013 Elsevier B.V. All rights reserved.

Mechanism of the protective effects of long chain n-alkyl glucopyranosides against ultrasound-induced cytolysis of HL-60 cells.

PubMed

Cheng, Jason Y; Riesz, Peter

2007-07-01

Recently it has been shown that long chain (C5-C8) n-alkyl glucopyranosides completely inhibit ultrasound-induced cytolysis [J.Z. Sostaric, N. Miyoshi, P. Riesz, W.G. DeGraff, and J.B. Mitchell, Free Radical Biol. Med., 39 (2005) 1539]. This protective effect has possible applications in HIFU (high intensity focused ultrasound) for tumor treatment, and in ultrasound assisted drug delivery and gene therapy. n-Alkyl glucopyranosides with hexyl (5mM), heptyl (3mM), octyl (2mM) n-alkyl chains protected 100% of HL-60 cells in vitro from 1.057 MHz ultrasound-induced cytolysis under a range of conditions that resulted in 35-100% cytolysis in the absence of glucopyranosides. However the hydrophilic methyl-beta-d-glucopyranoside did not protect cells. The surface active n-alkyl glucopyranosides accumulate at the gas-liquid interface of cavitation bubbles. The OH radicals and H atoms formed in collapsing cavitation bubbles react by H-atom abstraction from either the n-alkyl chain or the glucose moiety of the n-alkyl glucopyranosides. Owing to the high concentration of the long chain surfactants at the gas-liquid interface of cavitation bubbles, the initially formed carbon radicals on the alkyl chains are transferred to the glucose moieties to yield radicals which react with oxygen leading to the formation of hydrogen peroxide. In this work, we find that the sonochemically produced hydrogen peroxide yields from oxygen-saturated solutions of long chain (hexyl, octyl) n-alkyl glucopyranosides at 614 kHz and 1.057 MHz ultrasound increase with increasing n-alkyl glucopyranoside concentration but are independent of concentration for methyl-beta-D-glucopyranoside. These results are consistent with the previously proposed mechanism of sonoprotection [J.Z. Sostaric, N. Miyoshi, P. Riesz, W.G. DeGraff, and J.B. Mitchell, Free Radical Biol. Med., 39 (2005) 1539]. This sequence of events prevents sonodynamic cell killing by initiation of lipid peroxidation chain reactions in cellular

A new procedure for N1-alkylation of imidazolidin-4-ones and its NMR characterization

NASA Astrophysics Data System (ADS)

Vale, Nuno; Figueiredo, Patrícia

2016-12-01

N1-unsubstituted imidazolidin-4-ones of primaquine (PQ) can be stabilized by N1-alkylation under basic conditions. Here we report the development, with our conditions, of peptidomimetic derivatives of PQ with L-amino acid and alkyl derivatives. The new derivatives represent potential new therapeutics for use against protozoan parasites, through enzymatic protection of aminopeptidases.

Neighbor-directed histidine N(τ) alkylation. A route to imidazolium-containing phosphopeptide macrocycles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Wen-Jian; Park, Jung-Eun; Grant, Robert

2015-07-07

Our recently discovered, selective, on-resin route to N(τ)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. These cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Furthermore, neighbor-directed histidine N(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.

Mass spectrometry identification of alkyl-substituted pyrazines produced by Pseudomonas spp. isolates obtained from wine corks.

PubMed

Bañeras, Lluís; Trias, Rosalia; Godayol, Anna; Cerdán, Laura; Nawrath, Thorben; Schulz, Stefan; Anticó, Enriqueta

2013-06-15

We investigated the pyrazine production of 23 Pseudomonas isolates obtained from cork in order to assess their implications in off-flavour development. Off-flavour development in cork stoppers is a crucial process in maintaining the high quality of some wines. Pyrazine production was analyzed by headspace solid-phase-microextraction (HS-SPME) and gas chromatography coupled with mass spectrometry (GC-MS). Five out of the 23 isolates, i.e. Pseudomonas koreensis TCA20, Pseudomonas palleroniana TCA16, Pseudomonas putida TCA23 and N7, and Pseudomonas stutzeri TRA27a were able to produce branched alkyl-substituted pyrazines. For isolates N7 and TCA16, 14 compounds could be identified as pyrazines. The use of mineral media supplemented with different carbon and nitrogen sources resulted in changes in the pyrazine production capacity. In the two strains the amount of pyrazines produced was higher with glucose and decreased significantly with lactate. In all cases, 2,5-di(1-methylethyl)pyrazine was found to be dominant and independent of amino acid addition, suggesting a completely de novo synthesis. Aroma descriptions of most alkyl substituted pyrazines include mild vegetal aromas, not necessarily undesirable for the cork manufacturing industry. Methoxypyrazines, exhibiting earthy and musty aromas, could not be detected in any of the strains analysed. Copyright © 2012 Elsevier Ltd. All rights reserved.

N-Alkyl Urea Hydroxamic Acids as a New Class of Peptide Deformylase Inhibitors with Antibacterial Activity

PubMed Central

Hackbarth, Corinne J.; Chen, Dawn Z.; Lewis, Jason G.; Clark, Kirk; Mangold, James B.; Cramer, Jeffrey A.; Margolis, Peter S.; Wang, Wen; Koehn, Jim; Wu, Charlotte; Lopez, S.; Withers III, George; Gu, Helen; Dunn, Elina; Kulathila, R.; Pan, Shi-Hao; Porter, Wilma L.; Jacobs, Jeff; Trias, Joaquim; Patel, Dinesh V.; Weidmann, Beat; White, Richard J.; Yuan, Zhengyu

2002-01-01

Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P1′ site. Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at the P1′ site. Compounds with MICs of ≤4 μg/ml against gram-positive and gram-negative pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae, have been identified. The concentrations needed to inhibit 50% of enzyme activity (IC50s) for Escherichia coli Ni-PDF were ≤0.1 μM, demonstrating the specificity of the inhibitors. In addition, these compounds were very selective for PDF, with IC50s of consistently >200 μM for matrilysin and other mammalian metalloproteases. Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity. One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 Å. This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents. PMID:12183225

40 CFR 721.10145 - Modified reaction products of alkyl alcohol, halogenated alkane, substituted epoxide, and amino...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Modified reaction products of alkyl... Modified reaction products of alkyl alcohol, halogenated alkane, substituted epoxide, and amino compound... identified generically as modified reaction products of alkyl alcohol, halogenated alkane, substituted...

40 CFR 721.10145 - Modified reaction products of alkyl alcohol, halogenated alkane, substituted epoxide, and amino...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Modified reaction products of alkyl... Modified reaction products of alkyl alcohol, halogenated alkane, substituted epoxide, and amino compound... identified generically as modified reaction products of alkyl alcohol, halogenated alkane, substituted...

[Synthesis, characterization and fluorescent properties of copper phthalocyanine derivates substituted by aliphatic alcohol].

PubMed

Zhang, Liang; Xu, Qing-Feng; Lu, Jian-Mei; Yao, She-Chun

2007-04-01

A series of copper phthalocyanine derivatives substituted by aliphatic chain were obtained by the reaction of tetra-formyl chloride copper phthalocyanine and aliphatic alcohol such as n-butyl alcohol, n-amyl alcohol, n-hexyl alcohol, n-caprylic alcohol and lauryl alcohol. IR, UV-Vis, elemental analysis and 1H NMR verified the structures and substituting degree. The solubility and the relationship between fluorescence and concentration and substituting group were studied in organic solution. It was confirmed that the solubility in organic solution was improved greatly, the fluorescence did not change in linear according to the concentration and the fluorescence of copper phthalocyanine derivatives substituted by the long alkyl was stronger than that substituted by the relatively short alkyl.

40 CFR 721.10517 - Alkyl methacrylates, polymer with substituted carbomonocycle, hydroxymethyl acrylamide and...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl methacrylates, polymer with... Substances § 721.10517 Alkyl methacrylates, polymer with substituted carbomonocycle, hydroxymethyl acrylamide... reporting. (1) The chemical substance identified generically as alkyl methacrylates, polymer with...

Mechanism for stabilization of the molten globule state of papain by sodium n-alkyl sulfates: spectroscopic and calorimetric approaches.

PubMed

Chamani, J; Heshmati, M

2008-06-01

Papain exists in a molten globule (MG) state at pH 2 and in this state protein tends to aggregate in the presence of lower concentrations of guanidine hydrochloride (GuHCl). Such aggregation is prevented if low concentrations of sodium n-alkyl sulfates are also present in the buffer; in addition, stabilization of the protein is also induced. The guanidine hydrochloride and temperature-induced unfolding of papain, in the presence of n-alkyl sulfates, indicate stabilization of the protein as seen from the higher transition midpoints when monitored by fluorescence, circular dichroism, and differential scanning calorimetry. However, a similar phenomenon is not seen under neutral conditions in the presence of n-alkyl sulfate concentrations. The effect of n-alkyl sulfates on the structure of the MG state of papain was utilized to investigate the contribution of hydrophobic interaction to the stability of the MG state. The Td values of the MG states of papain in the presence of n-alkyl sulfates at different concentrations showed substantial variation. The enhancement of Td values at the stability criterion of MG states corresponded with increasing chain length of the cited n-alkyl sulfates. The present results suggest that the hydrophobic interactions play important roles in stabilizing and preventing the aggregation of the MG state of papain.

40 CFR 721.10038 - Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Trimellitic anhydride, polymer with... Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic... identified generically as trimellitic anhydride, polymer with substituted glycol, alkyl phenols and...

40 CFR 721.10038 - Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Trimellitic anhydride, polymer with... Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic... identified generically as trimellitic anhydride, polymer with substituted glycol, alkyl phenols and...

40 CFR 721.10038 - Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Trimellitic anhydride, polymer with... Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic... identified generically as trimellitic anhydride, polymer with substituted glycol, alkyl phenols and...

40 CFR 721.10038 - Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Trimellitic anhydride, polymer with... Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic... identified generically as trimellitic anhydride, polymer with substituted glycol, alkyl phenols and...

40 CFR 721.10038 - Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Trimellitic anhydride, polymer with... Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic... identified generically as trimellitic anhydride, polymer with substituted glycol, alkyl phenols and...

40 CFR 721.9220 - Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reaction products of secondary alkyl... Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric acid... substances identified generically as reaction products of secondary alkyl amines with a substituted...

40 CFR 721.9220 - Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reaction products of secondary alkyl... Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric acid... substances identified generically as reaction products of secondary alkyl amines with a substituted...

Activated N-nitrosocarbamates for regioselective synthesis of N-nitrosoureas.

PubMed

Martinez, J; Oiry, J; Imbach, J L; Winternitz, F

1982-02-01

A practical and convenient method for synthesizing antitumor compounds, N-alkyl-N-nitrosoureas, regioselectively nitrosated on the nitrogen atom bearing the alkyl group is proposed. N-Alkyl-N-nitrosocarbamates are interesting intermediates in these syntheses and yield, by reaction with amino compounds, the regioselectively nitrosated N-alkyl-N-nitrosoureas. As an interesting example, N,N'-bis[(2-chloroethyl)nitrosocarbamoyl]cystamine, a new attractive oncostatic derivative, has been prepared. The cytotoxic activity of these various compounds were tested on L1210 leukemia.

Cooperative alpha-helix formation of beta-lactoglobulin induced by sodium n-alkyl sulfates.

PubMed

Chamani, J; Moosavi-Movahedi, A A; Rajabi, O; Gharanfoli, M; Momen-Heravi, M; Hakimelahi, G H; Neamati-Baghsiah, A; Varasteh, A R

2006-01-01

It is generally assumed that folding intermediates contain partially formed native-like secondary structures. However, if we consider the fact that the conformational stability of the intermediate state is simpler than that of the native state, it would be expected that the secondary structures in a folding intermediate would not necessarily be similar to those of the native state. beta-Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly high intrinsic preference for alpha-helical structure. The formation of non-native alpha-helical intermediate of beta-lactoglobulin was induced by n-alkyl sulfates including sodium octyl sulfate, SOS; sodium decyl sulfate, SDeS; sodium dodecyl sulfate, SDS; and sodium tetradecyl sulfate, STS at special condition. The effect of n-alkyl sulfates on the structure of native beta-lactoglobulin at pH 2 was utilized to investigate the contribution of hydrophobic interactions to the stability of non-native alpha-helical intermediate. The addition of various concentrations of n-alkyl sulfates to the native state of beta-lactoglobulin (pH 2) appears to support the stabilized form of non-native alpha-helical intermediate at pH 2. The m values of the intermediate state of beta-lactoglobulin by SOS, SDeS, SDS and STS showed substantial variation. The enhancement of m values as the stability criterion of non-native alpha-helical intermediate state corresponded with increasing chain length of the cited n-alkyl sulfates. The present results suggest that the folding reaction of beta-lactoglobulin follows a non-hierarchical mechanism and hydrophobic interactions play important roles in stabilizing the non-native alpha-helical intermediate state.

METABOLISM OF N-ALKYLATED SPERMINE ANALOGUES BY POLYAMINE AND SPERMINE OXIDASES

PubMed Central

Häkkinen, Merja R.; Hyvönen, Mervi T.; Auriola, Seppo; Casero, Robert A.; Vepsäläinen, Jouko; Khomutov, Alex R.; Alhonen, Leena; Keinänen, Tuomo A.

2010-01-01

SUMMARY N-alkylated polyamine analogues have potential as anticancer and antiparasitic drugs. However, their metabolism in the host has remained incompletely defined thus potentially limiting their utility. Here, we have studied the degradation of three different spermine analogues N,N′-bis-(3-ethylaminopropyl)butane-1,4-diamine (DESPM), N-(3-benzyl-aminopropyl)-N'-(3-ethylaminopropyl)butane-1,4-diamine (BnEtSPM) and N,N′-bis-(3-benzylaminopropyl)butane-1,4-diamine (DBSPM) and related mono-alkylated derivatives as substrates of recombinant human polyamine oxidase (APAO) and spermine oxidase (SMO). APAO and SMO metabolized DESPM to EtSPD (Km(APAO)=10μM, kcat(APAO)=1.1s−1 and Km(SMO)=28μM, kcat(SMO)=0.8s−1, respectively), metabolized BnEtSPM to EtSPD (Km(APAO)=0.9 μM, kcat(APAO)=1.1s−1 and Km(SMO)=51μM, kcat(SMO)=0.4s−1, respectively), and metabolized DBSPM to BnSPD (Km(APAO)=5.4μM, kcat(APAO)= 2.0s−1 and Km(SMO)=33μM, kcat(SMO)=0.3s−1, respectively). Interestingly, mono-alkylated spermine derivatives were metabolized by APAO and SMO to SPD (EtSPM Km(APAO)=16μM, kcat(APAO)=1.5s−1; Km(SMO)=25μM, kcat(SMO) =8.2s−1; BnSPM Km(APAO)=6.0μM, kcat(APAO)=2.8s−1; Km(SMO)=19μM, kcat(SMO)=0.8s−1, respectively). Surprisingly, E t S P D ( Km(APAO)=37μM, kcat(APAO)=0.1s−1; Km(SMO)=48μM, kcat(SMO)=0.05s−1) and BnSPD (Km(APAO)=2.5μM, kcat(APAO)=3.5s−1; Km(SMO)=60μM, kcat(SMO)=0.54s−1) were metabolized to SPD by both the oxidases. Furthermore, we studied the degradation of DESPM, BnEtSPM or DBSPM in the DU145 prostate carcinoma cell line. The same major metabolites EtSPD and/or BnSPD were detected both in the culture medium and intracellularly after 48 hours of culture. Moreover, EtSPM and BnSPM were detected from cell samples. Present data shows that inducible SMO parallel with APAO could play an important role in polyamine based drug action, i.e. degradation of parent drug and its metabolites, having significant impact on efficiency of

40 CFR 721.642 - Amines, N-(C14-18 and C16-16 unsaturated alkyl)] dipropylene-tri-, tripropylenetetra-, and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... substances amines, N-(C14-18 and C16-18 unsaturated alkyl)] dipropylenetri-, (PMN P-94-1244... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amines, N-(C14-18 and C16-16... Amines, N-(C14-18 and C16-16 unsaturated alkyl)] dipropylene-tri-, tripropylenetetra-, and...

Read-across of ready biodegradability based on the substrate specificity of N-alkyl polypropylene polyamine-degrading microorganisms.

PubMed

Geerts, R; van Ginkel, C G; Plugge, C M

2017-04-01

The biodegradation of N-alkyl polypropylene polyamines (NAPPs) was studied using pure and mixed cultures to enable read-across of ready biodegradability test results. Two Pseudomonas spp. were isolated from activated sludge with N-oleyl alkyl propylene diamine and N-coco alkyl dipropylene triamine, respectively. Both strains utilized all NAPPs tested as the sole source of carbon, nitrogen and energy for growth. Mineralization of NAPPs was independent of the alkyl chain length and the size of the polyamine moiety. NAPPs degraded in closed bottle tests (CBTs) using both river water and activated sludge. However, ready biodegradability of NAPPs with alkyl chain lengths of 16-18 carbon atoms and polyamine moieties with three and four nitrogen atoms could not be demonstrated. Biodegradation in the CBT was hampered by their limited bioavailability, making assessment of the true ready biodegradability of these highly adsorptive surfactants impossible. All NAPPs are therefore classified as readily biodegradable through read-across. Read-across is justified by the broad substrate specificity of NAPP-degrading microorganisms, their omnipresence and the mineralization of NAPPs.

Catalytic dehydroaromatization of n-alkanes by pincer-ligated iridium complexes

NASA Astrophysics Data System (ADS)

Ahuja, Ritu; Punji, Benudhar; Findlater, Michael; Supplee, Carolyn; Schinski, William; Brookhart, Maurice; Goldman, Alan S.

2011-02-01

Aromatic hydrocarbons are among the most important building blocks in the chemical industry. Benzene, toluene and xylenes are obtained from the high temperature thermolysis of alkanes. Higher alkylaromatics are generally derived from arene-olefin coupling, which gives branched products—that is, secondary alkyl arenes—with olefins higher than ethylene. The dehydrogenation of acyclic alkanes to give alkylaromatics can be achieved using heterogeneous catalysts at high temperatures, but with low yields and low selectivity. We present here the first catalytic conversion of n-alkanes to alkylaromatics using homogeneous or molecular catalysts—specifically ‘pincer’-ligated iridium complexes—and olefinic hydrogen acceptors. For example, the reaction of n-octane affords up to 86% yield of aromatic product, primarily o-xylene and secondarily ethylbenzene. In the case of n-decane and n-dodecane, the resulting alkylarenes are exclusively unbranched (that is, n-alkyl-substituted), with selectivity for the corresponding o-(n-alkyl)toluene.

Substitutional and interstitial oxygen in wurtzite GaN

NASA Astrophysics Data System (ADS)

Wright, A. F.

2005-11-01

Density-functional theory was used to compute energy-minimum configurations and formation energies of substitutional and interstitial oxygen (O) in wurtzite GaN. The results indicate that O substituted at a N site (ON) acts as a single donor with the ionized state (ON+1) being the most stable O state in p-type GaN. In n-type GaN, interstitial O (OI) is predicted to be a double acceptor and O substituted at a Ga site (OGa) is predicted to be a triple acceptor. The formation energies of these two species are comparable to that of ON in n-type GaN and, as such, they should form and compensate the ON donors. The extent of compensation was estimated for both Ga-rich and N-rich conditions with a total O concentration of 1017cm-3. Ga-rich conditions yielded negligible compensation and an ON concentration in excess of 9.9×1016cm-3. N-rich conditions yielded a 25% lower ON concentration, due to the increased stability of OI and OGa relative to ON, and moderate compensation. These findings are consistent with experimental results indicating that O acts as a donor in GaN(O). Complexes of ON with the Mg acceptor and OI with the Si donor were examined. Binding energies for charge-conserving reactions were ⩾0.5eV, indicating that these complexes can exist in equilibrium at room temperature. Complexes of ON with the Ga vacancy in n-type GaN were also examined and their binding energies were 1.2 and 1.4eV, indicating that appreciable concentrations can exist in equilibrium even at elevated temperatures.

The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: the influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents.

PubMed

Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L; Gündisch, Daniela

2013-12-01

3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for α4β2(∗) were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for α4β2(∗) possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Scope of Direct Alkylation of Gold Surface with Solutions of C1-C4 n-Alkylstannanes.

PubMed

Kaletová, Eva; Kohutová, Anna; Hajduch, Jan; Kaleta, Jiří; Bastl, Zdeněk; Pospíšil, Lubomír; Stibor, Ivan; Magnera, Thomas F; Michl, Josef

2015-09-23

Treatment of cleaned gold surfaces with dilute tetrahydrofuran or chloroform solutions of tetraalkylstannanes (alkyl = methyl, ethyl, n-propyl, n-butyl) or di-n-butylmethylstannyl tosylate under ambient conditions causes a self-limited growth of disordered monolayers consisting of alkyls and tin oxide. Extensive use of deuterium labeling showed that the alkyls originate from the stannane and not from ambient impurities, and that trialkylstannyl groups are absent in the monolayers, contrary to previous proposals. Methyl groups attached to the Sn atom are not transferred to the surface. Ethyl groups are transferred slowly, and propyl and butyl rapidly. In all cases, tin oxide is codeposited in submonolayer amounts. The monolayers were characterized by ellipsometry, contact angle goniometry, polarization modulated IR reflection absorption spectroscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy with ferrocyanide/ferricyanide, which revealed a very low charge-transfer resistance. The thermal stability of the monolayers and their resistance to solvents are comparable with those of an n-octadecanethiol monolayer. A preliminary examination of the kinetics of monolayer deposition from a THF solution of tetra-n-butylstannane revealed an approximately half-order dependence on the bulk solution concentration of the stannane, hinting that more than one alkyl can be transferred from a single stannane molecule. A detailed structure of the attachment of the alkyl groups is not known, and it is proposed that it involves direct single or multiple bonding of one or more C atoms to one or more Au atoms.

Synthesis, crystal structure determination, biological screening and docking studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases.

PubMed

Sultana, Nargis; Sarfraz, Muhammad; Tanoli, Saba Tahir; Akram, Muhammad Safwan; Sadiq, Abdul; Rashid, Umer; Tariq, Muhammad Ilyas

2017-06-01

Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N 1 -substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC 50 values toward AChE in submicromolar range (0.8µM and 0.6µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase. Copyright © 2017 Elsevier Inc. All rights reserved.

Enantioconvergent Cross-Couplings of Racemic Alkylmetal Reagents with Unactivated Secondary Alkyl Electrophiles: Catalytic Asymmetric Negishi α-Alkylations of N-Boc-pyrrolidine

PubMed Central

Cordier, Christopher J.; Lundgren, Rylan J.; Fu, Gregory C.

2013-01-01

Although enantioconvergent alkyl-alkyl couplings of racemic electrophiles have been developed, there have been no reports of the corresponding reactions of racemic nucleophiles. Herein, we describe Negishi cross-couplings of racemic α-zincated N-Boc-pyrrolidine with unactivated secondary halides, thus providing a one-pot, catalytic asymmetric method for the synthesis of a range of 2-alkylpyrrolidines (an important family of target molecules) from N-Boc-pyrrolidine, a commercially available precursor. Preliminary mechanistic studies indicate that two of the most straightforward mechanisms for enantioconvergence (a dynamic kinetic resolution of the organometallic coupling partner and a simple β-hydride elimination/β-migratory insertion pathway) are unlikely to be operative. PMID:23869442

40 CFR 721.10200 - Benzenacetonitrile, cyclohexylidene-alkyl substituted (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenacetonitrile, cyclohexylidene-alkyl substituted (generic). 721.10200 Section 721.10200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES...

Regioselective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones: screening of their biological activities against Ca(2+)-ATPase.

PubMed

Putatunda, Salil; Chakraborty, Srabasti; Ghosh, Swatilekha; Nandi, Pinki; Chakraborty, Supriya; Sen, Parimal C; Chakraborty, Arijit

2012-08-01

A regioselective N1-alkylation of 3,4-dihydropyrimidin-2(1H)-ones using a very efficient mild base Cs(2)CO(3) and alkyl halides at room temperature has been reported. The selectivity of this methodology is excellent and the yields of the alkylated products are very good. Furthermore inhibitory action of both the 3,4-dihydropyrimidin-2(1H)-ones and the N1-alkylated derivatives were tested on Ca(2+)-ATPase, which revealed that the parent compounds can act as Ca(2+)-ATPase inhibitors whereas the N1-alkylated derivatives are inefficient for this purpose. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Production of n-alkyl lipids in living plants and implications for the geologic past

NASA Astrophysics Data System (ADS)

Diefendorf, Aaron F.; Freeman, Katherine H.; Wing, Scott L.; Graham, Heather V.

2011-12-01

Leaf waxes (i.e., n-alkyl lipids or n-alkanes) are land-plant biomarkers widely used to reconstruct changes in climate and the carbon isotopic composition of the atmosphere. There is little information available, however, on how the production of leaf waxes by different kinds of plants might influence the abundance and isotopic composition of n-alkanes in sedimentary archives. This lack of information increases uncertainty in interpreting n-alkyl lipid abundance and δ 13C signals in ancient settings. We provide here n-alkyl abundance distributions and carbon isotope fractionation data for deciduous and evergreen angiosperm and gymnosperm leaves from 46 tree species, representing 24 families. n-Alkane abundances are significantly higher in angiosperms than gymnosperms; many of the gymnosperm species investigated did not produce any n-alkanes. On average, deciduous angiosperms produce 200 times more n-alkanes than deciduous gymnosperms. Although differences between angiosperms and gymnosperms dominate the variance in n-alkane abundance, leaf life-span is also important, with higher n-alkane abundances in longer-lived leaves. n-Alkanol abundances covary with n-alkanes, but n-alkanoic acids have similar abundances across all plant groups. Isotopic fractionation between leaf tissue and individual alkanes ( ɛlipid) varies by as much as 10‰ among different chain lengths. Overall, ɛlipid values are slightly lower (-4.5‰) for angiosperm than for gymnosperm (-2.5‰) n-alkanes. Angiosperms commonly express slightly higher Δleaf (photosynthetic discrimination) relative to gymnosperms under similar growth conditions. As a result, angiosperm n-alkanes are expected to be generally 3-5‰ more depleted in 13C relative to gymnosperm alkanes for the same locality. Differences in n-alkane production indicate the biomarker record will largely (but not exclusively) reflect angiosperms if both groups were present, and also that evergreen plants will likely be overrepresented

REVISITING CLASSICAL NUCLEOPHILIC SUBSTITUTIONS IN AQUEOUS MEDIUM: MICROWAVE-ASSISTED SYNTHESIS OF ALKYL AZIDES

EPA Science Inventory

An efficient and clean synthesis of alkyl azides using microwave (MW) radiation is described in aqueous medium by reacting alkyl halides or tosylates with alkali azides. This general and expeditious MW-enhanced approach to nucleophilic substitution reactions is applicable to the ...

Solvent systems with n-hexane and/or cyclohexane in countercurrent chromatography--Physico-chemical parameters and their impact on the separation of alkyl hydroxybenzoates.

PubMed

Englert, Michael; Vetter, Walter

2014-05-16

Countercurrent chromatography (CCC) is an efficient preparative separation technique based on the liquid-liquid distribution of compounds between two phases of a biphasic liquid system. The crucial parameter for the successful application is the selection of the solvent system. Especially for nonpolar analytes the selection options are limited. On the search for a suitable solvent system for the separation of an alkyl hydroxybenzoate homologous series, we noted that the substitution of cyclohexane with n-hexane was accompanied with unexpected differences in partitioning coefficients of the individual analytes. In this study, we investigated the influence of the subsequent substitution of n-hexane with cyclohexane in the n-hexane/cyclohexane/tert-butylmethylether/methanol/water solvent system family. Exact phase compositions and polarity, viscosity and density differences were determined to characterize the different mixtures containing n-hexane and/or cyclohexane. Findings were confirmed by performing CCC separations with different mixtures, which led to baseline resolution for positional isomers when increasing the amount of cyclohexane while the resolution between two pairs of structural isomers decreased. With the new methodology described, structurally similar compounds could be resolved by choosing a certain ratio of n-hexane to cyclohexane. Copyright © 2014 Elsevier B.V. All rights reserved.

40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... are: (i) Industrial, commercial, and consumer activities. Requirements as specified in § 721.80(s... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted alkyl phosphine oxide (generic). 721.10087 Section 721.10087 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

Chiral Brønsted Base-Promoted Nitroalkane Alkylation: Enantioselective Synthesis of sec-Alkyl-3-Substituted Indoles

PubMed Central

Dobish, Mark C.; Johnston, Jeffrey N.

2010-01-01

A Brønsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base. PMID:21090654

Intramolecular cyclization of N-phenyl N'(2-chloroethyl)ureas leads to active N-phenyl-4,5-dihydrooxazol-2-amines alkylating β-tubulin Glu198 and prohibitin Asp40.

PubMed

Trzeciakiewicz, Anna; Fortin, Sébastien; Moreau, Emmanuel; C-Gaudreault, René; Lacroix, Jacques; Chambon, Christophe; Communal, Yves; Chezal, Jean-Michel; Miot-Noirault, Elisabeth; Bouchon, Bernadette; Degoul, Françoise

2011-05-01

The cyclization of anticancer drugs into active intermediates has been reported mainly for DNA alkylating molecules including nitrosoureas. We previously defined the original cytotoxic mechanism of anticancerous N-phenyl-N'-(2-chloroethyl)ureas (CEUs) that involves their reactivity towards cellular proteins and not against DNA; two CEU subsets have been shown to alkylate β-tubulin and prohibitin leading to inhibition of cell proliferation by G₂/M or G₁/S cell cycle arrest. In this study, we demonstrated that cyclic derivatives of CEUs, N-phenyl-4,5-dihydrooxazol-2-amines (Oxas) are two- to threefold more active than CEUs and share the same cytotoxic properties in B16F0 melanoma cells. Moreover, the CEU original covalent binding by an ester linkage on β-tubulin Glu198 and prohibitin Asp40 was maintained with Oxas. Surprisingly, we observed that Oxas were spontaneously formed from CEUs in the cell culture medium and were also detected within the cells. Our results suggest that the intramolecular cyclization of CEUs leads to active Oxas that should then be considered as the key intermediates for protein alkylation. These results will be useful for the design of new prodrugs for cancer chemotherapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular structure, supramolecular organization and thermotropic phase behavior of N-acylglycine alkyl esters with matched acyl and alkyl chains.

PubMed

Reddy, S Thirupathi; Swamy, Musti J

2017-11-01

N-Acylglycines (NAGs), the endogenous single-tailed lipids present in rat brain and other mammalian tissues, play significant roles in cell physiology and exhibit interesting pharmacological properties. In the present study, a homologous series of N-acylglycine alkyl esters (NAGEs) with matched chains were synthesized and characterized. Results of differential scanning calorimetric studies revealed that all NAGEs exhibit a single sharp phase transition and that the transition enthalpy and entropy show a linear dependence on the N-acyl and ester alkyl chain length. The structure of N-myristoylglycine myristyl ester (NMGME), solved by single-crystal X-ray diffraction, showed that the molecule adopts a linear geometry and revealed that the structure of N-myristoyl glycyl moiety in NMGME is identical to that in N-myristoylglycine. The molecules are packed in layers with the polar functional groups of the ester and amide functionalities located at the center of the layer. The crystal packing is stabilized by NH⋯O hydrogen bonds between the amide CO and NH groups of adjacent molecules as well as by CH⋯O hydrogen bonds between the amide carbonyl and the methylene CH adjacent to the ester carbonyl of neighboring molecules as well as between ester carbonyl and methylene group of the glycine moiety of adjacent molecules. Powder X-ray diffraction studies showed a linear dependence of the d-spacings on the acyl chain length, suggesting that all NAGEs adopt a structure similar to the packing exhibited in the crystal lattice of NMGME. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthetic, structural, and computational investigations of N-alkyl benzo-2,1,3-selenadiazolium iodides and their supramolecular aggregates.

PubMed

Lee, Lucia M; Corless, Victoria B; Tran, Michael; Jenkins, Hilary; Britten, James F; Vargas-Baca, Ignacio

2016-02-28

Despite their versatility, the application of telluradiazoles as supramolecular building blocks is considerably constrained by their sensitivity to moisture. Albeit more robust, their selenium analogues form weaker supramolecular interactions. These, however, are enhanced when one nitrogen atom is bonded to an alkyl group. Here we investigate general methods for the synthesis of such derivatives. Methyl, iso-propyl and tert-butyl benzo-2,1,3-selenadiazolium cations were prepared by direct alkylation or cyclo-condensation of the alkyl-phenylenediamine with selenous acid. While the former reaction only proceeds with the primary and tertiary alkyl iodides, the latter is very efficient. Difficulties reported in earlier literature are attributable to the formation of adducts of benzoselenadiazole with its alkylated cations and side reactions initiated by aerobic oxidation of iodide. However, the cations themselves are resilient to oxidation and stable in acidic to neutral aqueous medium. X-ray crystallography was used in the identification and characterization of the following compounds: [C6H4N2(R)Se](+)X(-), (R = CH(CH3)2, C(CH3)3; X = I(-), I3(-)], [C6H4N2(CH3)Se](+)I(-), and [C6H4N2Se][C6H4N2(CH3)Se]2I2. Formation of SeN secondary bonding interactions (chalcogen bonds) was only observed in the last structure as anion binding to selenium is a strong competitor. The relative strengths of those forces and the structural preferences they enforce were assessed with DFT-D3 calculations supplemented by AIM analysis of the electron density.

40 CFR 721.9925 - Aminoethylethylene urea methacrylamide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Aminoethylethylene urea methacrylamide... Substances § 721.9925 Aminoethylethylene urea methacrylamide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an aminoethylethylene urea...

Gas chromatography-mass spectrometric studies of O-alkyl O-2-(N,N-dialkylamino) ethyl alkylphosphonites(phosphonates) for chemical weapons convention verification.

PubMed

Saeidian, Hamid; Babri, Mehran; Ramezani, Atefeh; Ashrafi, Davood; Sarabadani, Mansour; Naseri, Mohammad Taghi

2013-01-01

The electron ionization (EI) mass spectra of a series of O-alkyl O-2-(N,N-dialkylaminolethyl alkylphosphonites(phosphonates), which are precursors of nerve agents, were studied for Chemical Weapons Convention (CWC) verification. General El fragmentation pathways were constructed and discussed. Proposed fragment structures were confirmed through analyzing fragment ions of deuterated analogs and density functional theory (DFT) calculations. The observed fragment ions are due to different fragmentation pathways such as hydrogen and McLafferty+1 rearrangements, alkene, amine and alkoxy elimination by alpha- or beta-cleavage process. Fragment ions distinctly allow unequivocal identification of the interested compounds including those of isomeric compounds. The presence and abundance of fragment ions were found to depend on the size and structure of the alkyl group attached to nitrogen, phosphorus and oxygen atoms.

Nitrosamine-induced carcinogenesis. The alkylation of N-7 of guanine of nucleic acids of the rat by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate

PubMed Central

Swann, P. F.; Magee, P. N.

1971-01-01

1. The extent of ethylation of N-7 of guanine in the nucleic acids of rat tissue in vivo by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate was measured. 2. All compounds produced measurable amounts of 7-ethyl-guanine. 3. A single dose of diethylnitrosamine or N-ethyl-N-nitrosourea produced tumours of the kidney in the rat. Three doses of ethyl methanesulphonate produced kidney tumours, but a single dose did not. 4. A single dose of diethylnitrosamine produced twice as much ethylation of N-7 of guanine in DNA of kidney as did N-ethyl-N-nitrosourea. A single dose of both compounds induced kidney tumours, although of a different histological type. 5. A single dose of ethyl methanesulphonate produced ten times as much ethylation of N-7 of guanine in kidney DNA as did N-ethyl-N-nitrosourea without producing tumours. 6. The relevance of these findings to the hypothesis that alkylation of a cellular component is the mechanism of induction of tumours by nitroso compounds is discussed. PMID:5145908

L-β-N-methylamino-l-alanine (BMAA) nitrosation generates a cytotoxic DNA damaging alkylating agent: An unexplored mechanism for neurodegenerative disease.

PubMed

Potjewyd, G; Day, P J; Shangula, S; Margison, G P; Povey, A C

2017-03-01

L-β-N-methylamino-l-alanine (BMAA) is a non-proteinic amino acid, that is neurotoxic in vitro and in animals, and is implicated in the causation of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC) on Guam. Given that natural amino acids can be N-nitrosated to form toxic alkylating agents and the structural similarity of BMAA to other amino acids, our hypothesis was that N-nitrosation of BMAA might result in a toxic alkylating agent, providing a novel mechanistic hypothesis for BMAA action. We have chemically nitrosated BMAA with sodium nitrite to produce nitrosated BMAA (N-BMAA) which was shown to react with the alkyl-trapping agent, 4-(p-nitrobenzyl)pyridine, cause DNA strand breaks in vitro and was toxic to the human neuroblastoma cell line SH-SY5Y under conditions in which BMAA itself was minimally toxic. Our results indicate that N-BMAA is an alkylating agent and toxin suggesting a plausible and previously unrecognised mechanism for the neurotoxic effects of BMAA. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamic adsorption properties of n-alkyl glucopyranosides determine their ability to inhibit cytolysis mediated by acoustic cavitation.

PubMed

Sostaric, Joe Z; Miyoshi, Norio; Cheng, Jason Y; Riesz, Peter

2008-10-09

Suspensions of human leukemia (HL-60) cells readily undergo cytolysis when exposed to ultrasound above the acoustic cavitation threshold. However, n-alkyl glucopyranosides (hexyl, heptyl, and octyl) completely inhibit ultrasound-induced (1057 kHz) cytolysis (Sostaric, et al. Free Radical Biol. Med. 2005, 39, 1539-1548). The efficacy of protection from ultrasound-induced cytolysis was determined by the n-alkyl chain length of the glucopyranosides, indicating that protection efficacy depended on adsorption of n-alkyl glucopyranosides to the gas/solution interface of cavitation bubbles and/or the lipid membrane of cells. The current study tests the hypothesis that "sonoprotection" (i.e., protection of cells from ultrasound-induced cytolysis) in vitro depends on the adsorption of glucopyranosides at the gas/solution interface of cavitation bubbles. To test this hypothesis, the effect of ultrasound frequency (from 42 kHz to 1 MHz) on the ability of a homologous series of n-alkyl glucopyranosides to protect cells from ultrasound-induced cytolysis was investigated. It is expected that ultrasound frequency will affect sonoprotection ability since the nature of the cavitation bubble field will change. This will affect the relative importance of the possible mechanisms for ultrasound-induced cytolysis. Additionally, ultrasound frequency will affect the lifetime and rate of change of the surface area of cavitation bubbles, hence the dynamically controlled adsorption of glucopyranosides to their surface. The data support the hypothesis that sonoprotection efficiency depends on the ability of glucopyranosides to adsorb at the gas/solution interface of cavitation bubbles.

Ionic liquids as refolding additives: N′-alkyl and N′-(ω-hydroxyalkyl) N-methylimidazolium chlorides

PubMed Central

Lange, Christian; Patil, Ganesh; Rudolph, Rainer

2005-01-01

The purpose of this work was to investigate the influence of a series of N′-alkyl and N′-(ω-hydroxy-alkyl)-N-methylimidazolium chlorides on the renaturation of two model proteins, namely hen egg white lysozyme and the single-chain antibody fragment ScFvOx. All tested ionic liquids acted as refolding enhancers, with varying efficacies and efficiencies. The results of the refolding screening could be interpreted by taking into account the effect of the studied ionic liquids on protein aggregation, together with the systematic variations of their influence on the stability of native proteins in solution. More hydrophobic imidazolium cations carrying longer alkyl chains were increasingly destabilizing, while terminal hydroxylation of the alkyl chain made the salts more compatible with protein stability. The studied ionic liquids can be classified as preferentially bound, slightly to moderately chaotropic cosolvents for proteins. PMID:16195554

Methacrylamide grafted elastomer composites reinforced with biobased particles

USDA-ARS?s Scientific Manuscript database

Modulus of rubber can be improved with grafting of unsaturated monomers. To increase the modulus of bio-based rubber composites, methacrylamide was grafted onto natural rubber composites reinforced with bio-based hydrophilic particles. Rubber particles in water were modified with methacrylamide usin...

Anti-cancer agents based on N-acyl-2, 3-dihydro-1H-pyrrolo[2,3-b] quinoline derivatives and a method of making

DOEpatents

Gakh, Andrei; Krasavin, Mikhail; Karapetian, Ruben; Rufanov, Konstantin A; Konstantinov, Igor; Godovykh, Elena; Soldatkina, Olga; Sosnov, Andrey V

2013-04-16

The present disclosure relates to novel compounds that can be used as anti-cancer agents in the prostate cancer therapy. In particular, the invention relates to N-acyl derivatives of 2,3-dihydro-1H-pyrrolo[2,3-b]quinolines having the structural Formula (I), ##STR00001## stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof. The meaning of R1 is independently selected from H; C1-C6 Alkyl, cyclo-Alkyl or iso-Alkyl substituents; R2 is selected from C1-C6 Alkyl, cyclo-Alkyl or iso-Alkyl; substituted or non-substituted, fused or non-fused to substituted or non-substituted aromatic ring, aryl or heteroaryl groups. The invention also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

40 CFR 721.10022 - Benzenamine, N-phenyl-, ar′-(C9-rich C8-10-branched alkyl) derivs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Significant New Uses for Specific Chemical Substances § 721.10022 Benzenamine, N-phenyl-, ar′-(C9-rich C8-10... chemical substance identified as benzenamine, N-phenyl-, ar′-(C9-rich C8-10-branched alkyl) derivs (PMN P...

Doubly 15N-substituted diazenylium: THz laboratory spectra and fractionation models

NASA Astrophysics Data System (ADS)

Dore, L.; Bizzocchi, L.; Wirström, E. S.; Degli Esposti, C.; Tamassia, F.; Charnley, S. B.

2017-07-01

Context. Isotopic fractionation in dense molecular cores has been suggested as a possible origin of large 14N/15N ratio variations in solar system materials. While chemical models can explain some observed variations with different fractionation patterns for molecules with -NH or -CN functional groups, they fail to reproduce the observed ratios in diazenylium (N2H+). Aims: Observations of doubly 15N-substituted species could provide important constraints and insights for theoretical chemical models of isotopic fractionation. However, spectroscopic data are very scarce. Methods: The rotational spectra of the fully 15N-substituted isopologues of the diazenylium ion, 15N2H+ and 15N2D+, have been investigated in the laboratory well into the THz region by using a source-modulation microwave spectrometer equipped with a negative glow discharge cell. An extended chemical reaction network has been used to estimate what ranges of 15N fractionation in doubly 15N-substituted species could be expected in the interstellar medium (ISM). Results: For each isotopologue of the H- and D-containing pair, nine rotational transitions were accurately measured in the frequency region 88 GHz-1.2 THz. The analysis of the spectrum provided very precise rest frequencies at millimeter and sub-millimeter wavelengths, useful for the radioastronomical identification of the rotational lines of 15N2H+ and 15N2D+ in the ISM.

40 CFR 721.10606 - Alkyl substituted alkanediol polymer with aliphatic and alicyclic diisocyanates (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl substituted alkanediol polymer... alkanediol polymer with aliphatic and alicyclic diisocyanates (generic). (a) Chemical substance and... substituted alkanediol polymer with aliphatic and alicyclic diisocyanates (PMN P-11-486) is subject to...

40 CFR 721.10606 - Alkyl substituted alkanediol polymer with aliphatic and alicyclic diisocyanates (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl substituted alkanediol polymer... alkanediol polymer with aliphatic and alicyclic diisocyanates (generic). (a) Chemical substance and... substituted alkanediol polymer with aliphatic and alicyclic diisocyanates (PMN P-11-486) is subject to...

N-Alkyl-PEI Functional Iron Oxide Nanocluster for Efficient siRNA Delivery**

PubMed Central

Liu, Gang; Xie, Jin; Zhang, Fan; Wang, Zhi-Yong; Luo, Kui; Zhu, Lei; Quan, Qi-Meng; Niu, Gang; Lee, Seulki

2013-01-01

Small interfering RNA (siRNA) is an emerging class of therapeutics, working by regulating the expression of a specific gene involved in disease progression. Despite the promises, effective transport of siRNA with minimal side effects remains a challenge. In this study, a non-viral nanoparticle gene carrier has been developed and its efficiency for siRNA delivery and transfection has been validated at both in vitro and in vivo levels. Such a nanocarrier, abbreviated as Alkyl-PEI2k-IO, was constructed with a core of iron oxide (IO) and a shell of alkylated PEI2000 (Alkyl-PEI2k). It was found to be able to bind with siRNA, resulting in well-dispersed nanoparticles with a controlled clustering structure and narrow size distribution. Electrophoresis studies showed that the Alkyl-PEI2k-IOs could retard siRNA completely at N/P ratios above 10, protect siRNA from enzymatic degradation in serum and release complexed siRNA efficiently in the presence of polyanionic heparin. The knockdown efficiency of the siRNA loaded nanocarriers was assessed with 4T1 cells stably expressing luciferase (fluc-4T1) and further, with a fluc-4T1 xenograft model. Significant downregulation of luciferase was observed, and unlike the high molecular weight analogs, the Alkyl-PEI2k coated IOs showed a good biocompatibility. In conclusion, Alkyl-PEI2k-IOs demonstrate highly efficient delivery of siRNA and an innocuous toxic profile, making it a potential carrier for gene therapy. PMID:21861295

Critical effects of alkyl chain length on fibril structures in benzene-trans(RR)- or (SS)-N,N'-alkanoyl-1,2-diaminocyclohexane gels.

PubMed

Sato, Hisako; Nakae, Takahiro; Morimoto, Kazuya; Tamura, Kenji

2012-02-28

Vibrational circular dichroism (VCD) spectra were recorded on benzene-d(6) gels formed by chiral low molecular mass gelators (LMGs), trans(RR)- or trans(SS)-N,N'-alkanoyl-1,2-diaminocyclohexane (denoted by RR-C(n) or SS-C(n), respectively; n = the number of carbon atoms in an introduced alkanoyl group). Attention was focused on the effects of alkyl chain length on the structures of the gels. When n was changed from 6 to 12, the signs of the coupled peaks around 1550 cm(-1) in the VCD spectra, which were assigned to the symmetric and asymmetric C=O stretching vibrations from the higher to lower wavenumber, respectively, critically depended on the alkyl chain length. In the case of RR-C(n), for example, the signs of the couplet were plus and minus for n = 8, 9, 10 and 12, while the signs of the same couplet were reversed for n = 6 and 7. The conformations of LMGs in fibrils were determined by comparing the observed IR and VCD spectra with those calculated for a monomeric molecule. The observed reversal of signs in the C=O couplet was rationalized in terms of the different modes of hydrogen bonding. In the case of C(8), C(9), C(10) and C(12), gelator molecules were stacked with their cyclohexyl rings in parallel, forming double anti-parallel chains of intermolecular hydrogen bonds using two pairs of >NH and >C=O groups. In case of C(6) and C(7), gelator molecules were stacked through a single chain of intermolecular hydrogen bonds using a pair of >NH and >C=O groups. The remaining pair of >NH and >C=O groups formed an intramolecular hydrogen bond.

How Does the Ionic Liquid Organizational Landscape Change when Nonpolar Cationic Alkyl Groups Are Replaced by Polar Isoelectronic Diethers?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kashyap, Hemant K.; Santos, Cherry S.; Daly, Ryan P.

2012-12-21

The X-ray scattering experiments and molecular dynamics simulations have been performed to investigate the structure of four room temperature ionic liquids (ILs) comprising the bis(trifluoromethylsulfonyl)amide (NTf 2 –) anion paired with the triethyloctylammonium (N 2228 +) and triethyloctylphosphonium (P 2228 +) cations and their isoelectronic diether analogs, the (2-ethoxyethoxy)ethyltriethylammonium (N 222(2O2O2) +) and (2-ethoxyethoxy)ethyltriethylphosphonium (P 222(2O2O2) +) cations. Agreement between simulations and experiments is good and permits a clear interpretation of the important topological differences between these systems. The first sharp diffraction peak (or prepeak) in the structure function S(q) that is present in the case of the liquids containingmore » the alkyl-substituted cations is absent in the case of the diether substituted analogs. Using different theoretical partitioning schemes for the X-ray structure function, we show that the prepeak present in the alkyl-substituted ILs arises from polarity alternations between charged groups and nonpolar alkyl tails. In the case of the diether substituted ILs, we find considerable curling of tails. Anions can be found with high probability in two different environments: close to the cationic nitrogen (phosphorus) and also close to the two ether groups. Moreover, for the two diether systems, anions are found in locations from which they are excluded in the alkyl-substituted systems. This removes the longer range (polar/nonpolar) pattern of alternation that gives rise to the prepeak in alkyl-substituted systems.« less

Synthesis and antifungal activities of 3-alkyl substituted thieno[2,3-d]pyrimidinones

NASA Astrophysics Data System (ADS)

Wang, H. M.; Deng, S. H.; Zheng, A. H.; Zhang, Q. Y.; Chen, X. B.; Zeng, X. H.; Hu, Y. G.

2016-08-01

The 3-aryl substituted thieno[2,3-d]pyrimidinones 3 by sequential reaction of iminophosphorane 1, aromatic isocyanates and various nucleophiles (HY), found some compounds showed good antitumor and antibacterial activities. Meanwhile, aliphatic isocyanates were applied in the reaction to prepare 3-alkyl substituted thieno[2,3- d]pyrimidinones, but there are no reports of their antifungal activities. As a continuation of our research for new biologically active heterocycles, we herein wish to report a facile synthesis and antifungal activities of 3-alkyl substituted thieno[2,3-d]pyrimidinones 6 via easily accessible iminophosphorane 1. The growth inhibitory effect of one concentration (50mg/L) of compounds 6 against five fungus(Fusarium oxysporium, Rhizoctonia solani, Colletotrichum gossypii, Gibberella zeae and Dothiorella gregaria) in vitro was tested by the method of toxic medium. Compound 6d showed the best inhibition rate against Gibberella zeae with 85.68%.

Design, Synthesis, and Biological Evaluation of Peptidomimetic N-Substituted Cbz-4-Hyp-Hpa-Amides as Novel Inhibitors of Plasmodium falciparum.

PubMed

Bacherikov, Valeriy A; Chittiboyina, Amar G; Avery, Mitchell A

2017-08-01

A new series of peptidomimetic N-substituted Cbz-4-Hyp-Hpa-amides were designed, synthesized, and evaluated for inhibition of the Plasmodium falciparum. Substituents on the N-atom of the amide group were selected alkyl-, allyl-, aryl-, 2-hydroxyethyl-, 2-cyanoethyl-, cyanomethyl-, 2-hydroxyethyl-, 2,2-diethoxyethyl-, or 2-ethoxy-2-oxoethylamino groups, and about of 40 new compounds were synthesized and evaluated for antiplasmodial activity in vitro. Antimalarial activity has been investigated as for the final peptide mimetics, and their immediate predecessors, carrying TBDMS or TBDPS protecting groups on 4-hydroxyproline residue and 18 derivatives exhibited toxicity against P. falciparum. Of these agents, compound 23e was shown to have potent antimalarial activity with IC 50 528 ng/ml. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Diastereoselective addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones

NASA Astrophysics Data System (ADS)

Uteuliyev, Maulen M.; Nguyen, Thien T.; Coltart, Don M.

2015-12-01

The α-alkylation of ketones and their derivatives by the addition of their corresponding enolates to alkyl halides is a fundamental synthetic transformation, but its utility is limited because the key bond-forming step proceeds in a bimolecular nucleophilic substitution fashion. Here we describe how an umpolung strategy that involves the addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones—directed by the alkoxide of the 1-azo-3-alkoxy propenes formed in situ via base-induced ring opening of the epoxide—leads to the syn-selective production of α-alkyl-β-hydroxy N-sulfonyl hydrazones with α-quaternary centres. This transformation is remarkable in its ability to incorporate an unprecedented range of carbon-based substituents, which include primary, secondary and tertiary alkyl, as well as alkenyl, aryl, allenyl and alkynyl groups. Subsequent hydrolysis of the β-hydroxy N-sulfonyl hydrazone products produces the corresponding β-hydroxy ketones. In addition to hydrolysis, the hydrazone products are poised to undergo numerous different known synthetic transformations via well-established chemistry, which would provide access to a wide array of useful structures.

Effect of polyoxyethylene n-alkyl ethers on carrier-mediated transport of lanthanide ions through cellulose triacetate membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugiura, Masaaki

1992-02-01

Fluxes of 14 kinds of lanthanides across cellulose triacetate membranes were determined by using mixtures of o-nitrophenyl n-octyl ether and a series of polyoxythylene n-alkyl ethers (POE ethers) as plasticizers, and hinokitiol as carrier. Effects of alkyl and polyoxyethylene (POE) chains of POE ether on the flux were demonstrated. The transport of the lanthanides was coupled to a flow of hydrogen ions. The POE ethers used (C{sub n}H{sub 2n+1}(OCH{sub 2}CH{sub 2}){sub x}OH, referred to as C{sub n}E{sub x}) were C{sub 10}E{sub 3}, C{sub 12}E{sub 3}, C{sub 14}E{sub 3}, C{sub 16}E{sub 3}, C{sub 12}E{sub 2}, C{sub 12}E{sub 4}, C{sub 12}E{sub 6}more » and C{sub 12}E{sub 8}, In all cases, high fluxes were observed for the lanthanides from samarium to lutetium. On the contrary, the fluxes for lanthanum to neodymium were extremely low. In experiments testing the effect of the alkyl chain, the order of the POE ethers in the lanthanide flux for samarium to lutetium was C{sub 12}E{sub 3} > C{sub 10}E{sub 3} > C{sub 14}E{sub 3} >C{sub 16}E{sub 3}. In experiments testing the effect of the POE chain, the flux decreased with an increase in the chain length.« less

Ruthenium-catalyzed alkylation of indoles with tertiary amines by oxidation of a sp3 C-H bond and Lewis acid catalysis.

PubMed

Wang, Ming-Zhong; Zhou, Cong-Ying; Wong, Man-Kin; Che, Chi-Ming

2010-05-17

Ruthenium porphyrins (particularly [Ru(2,6-Cl(2)tpp)CO]; tpp=tetraphenylporphinato) and RuCl(3) can act as oxidation and/or Lewis acid catalysts for direct C-3 alkylation of indoles, giving the desired products in high yields (up to 82% based on 60-95% substrate conversions). These ruthenium compounds catalyze oxidative coupling reactions of a wide variety of anilines and indoles bearing electron-withdrawing or electron-donating substituents with high regioselectivity when using tBuOOH as an oxidant, resulting in the alkylation of N-arylindoles to 3-{[(N-aryl-N-alkyl)amino]methyl}indoles (yield: up to 82%, conversion: up to 95%) and the alkylation of N-alkyl or N-H indoles to 3-[p-(dialkylamino)benzyl]indoles (yield: up to 73%, conversion: up to 92%). A tentative reaction mechanism involving two pathways is proposed: an iminium ion intermediate may be generated by oxidation of an sp(3) C-H bond of the alkylated aniline by an oxoruthenium species; this iminium ion could then either be trapped by an N-arylindole (pathway A) or converted to formaldehyde, allowing a subsequent three-component coupling reaction of the in situ generated formaldehyde with an N-alkylindole and an aniline in the presence of a Lewis acid catalyst (pathway B). The results of deuterium-labeling experiments are consistent with the alkylation of N-alkylindoles via pathway B. The relative reaction rates of [Ru(2,6-Cl(2)tpp)CO]-catalyzed oxidative coupling reactions of 4-X-substituted N,N-dimethylanilines with N-phenylindole (using tBuOOH as oxidant), determined through competition experiments, correlate linearly with the substituent constants sigma (R(2)=0.989), giving a rho value of -1.09. This rho value and the magnitudes of the intra- and intermolecular deuterium isotope effects (k(H)/k(D)) suggest that electron transfer most likely occurs during the initial stage of the oxidation of 4-X-substituted N,N-dimethylanilines. Ruthenium-catalyzed three-component reaction of N-alkyl/N-H indoles

Synthesis of 2-{(5-phenyl-1,3,4-Oxadiazol-2-yl)sulfanyl}-N-substituted acetamides as potential antimicrobial and hemolytic agents.

PubMed

Rehman, Aziz-ur; Abbasi, Muhammad Athar; Siddiqui, Sabahat Zahra; Ahmad, Irshad; Shahid, Muhammad; Subhani, Zinayyera

2016-05-01

A new series of N-substituted derivatives of 2-{(5-phenyl-1,3,4-Oxadiazol-2-yl)sulfanyl}acetamides was synthesized. The synthesis was carried out by converting benzoic acid (1) into ethyl benzoate (2), benzohydrazide (3) and then 5-pheny-1,3,4-Oxadiazol-2-thiol (4) step by st0ep. The target compounds 6a-p were synthesized by reaction of compound 4 with equimolar ratios of different N-alkyl/aryl substituted 2-bromoacetamide (5a-p) in the presence of DMF and sodium hydride (NaH). The spectral (EI-MS, IR, (1)H-NMR) characterization of all the synthesized compounds reveal their successful synthesis. The compounds were also screened for antimicrobial & hemolytic activity and most of them were found to be active against the selected microbial species at variable extent relative to reference standards. But 6h was the most active against the selected panel of microbes. This series showed less toxicity and may be considered for further biological screening and application trial except 6m, possessing higher cytotoxicity.

Access to 6a-Alkyl Aporphines: Synthesis of (±)-N-Methylguattescidine.

PubMed

Ku, Angela F; Cuny, Gregory D

2016-10-21

(-)-N-Methylguattescidine (3) is an alkaloid recently isolated from Fissistigma latifolium and assigned as a rare example of a 6a-alkyl aporphine. Herein, we report the synthesis of (±)-3 and the des-hydroxyl derivative 4 using our previously reported ortho-phenol arylation methodology mediated by the XPhos precatalyst as a key synthetic step. In addition, substituents on the aryl halide portion of the ortho-phenol arylation substrates significantly influenced the formation of an oxidized side product.

Enantioselective Synthesis of Chiral α-Azido and α-Aryloxy Quaternary Stereogenic Centers via the Phase-Transfer-Catalyzed α-Alkylation of α-Bromomalonates, Followed by SN2 Substitution.

PubMed

Kim, Doyoung; Ha, Min Woo; Hong, Suckchang; Park, Cheonhyoung; Kim, Byungsoo; Yang, Jewon; Park, Hyeung-Geun

2017-05-05

A new efficient synthetic method for chiral α-azido-α-alkylmalonates and α-aryloxy-α-alkylmalonates was developed. The enantioselective α-alkylation of diphenylmethyl tert-butyl α-bromomalonate under phase-transfer catalytic conditions [(S,S)-3,4,5-trifluorophenyl-NAS bromide, 50% KOH, toluene, and -40 °C) provided the corresponding α-bromo-α-alkylmalonates in high chemical yields (≤98%) and high optical yields (≤99% ee). The resulting α-alkylated products were converted to α-azido-α-alkylmalonates (≤96%, ≤97% ee) and α-aryloxy-α-alkylmalonates (≤79%, ≤93% ee) by S N 2 substitution with sodium azide and aryloxides, respectively.

Development of 2′-substituted (2S,1′R,2′S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists

PubMed Central

Risgaard, Rune; Nielsen, Simon D.; Hansen, Kasper B.; Jensen, Christina M.; Nielsen, Birgitte; Traynelis, Stephen F.; Clausen, Rasmus P.

2013-01-01

A series of 2′-substituted analogues of the selective NMDA receptor ligand (2S,1′R,2′S)-2-(carboxycyclopropyl)glycine ((S)-CCG-IV) have been designed, synthesized and pharmacologically characterized. The design was based on a docking study hypothesizing that substituents in the 2′-position would protrude into a region where differences among the NMDA receptor GluN2 subunits exist. Various synthetic routes were explored, and two different routes provided a series of alkyl-substituted analogues. Pharmacological characterization revealed that these compounds are NMDA receptor agonists and that potency decreases with increasing size of the alkyl groups. Variations in agonist activity are observed at the different recombinant NMDA receptor subtypes. This study demonstrates that it is possible to introduce substituents in the 2′-position of (S)-CCG-IV while maintaining agonist activity and that variation among NMDA receptor subtypes may be achieved by probing this region of the receptor. PMID:23614571

Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in granular sludge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donlon, B.A.; Razo-Flores, E.; Field, J.A.

1995-11-01

N-substituted aromatics are important priority pollutants entering the environment primarily through anthropogenic activities associated associated with the industrial production of dyes, explosives, pestides, and pharmaceuticals. Anaerobic treatment of wastewaters discharged by these industries could potentially be problematical as a result of the high toxicity of N-substituted aromatics. The objective of this study was to examine the structure-toxicity relationship of N-substituted aromatic compounds to acetoclastic methanogenic bacteria. The toxicity was assayed to serum flasks by measuring methane production in granular sludge. Unacclimated cultures were used to minimize the biotransformation of the toxic organic chemicals during the test. The nature and themore » degree of the aromatic substitution were observed to have a profound effect on the toxicity of the test compound. Nitroaromatic compounds were, on the average, over 500-fold more toxic than their corresponding aromatic amines. Considering the facile reduction of nitro groups by anerobic microorganisms, a dramatic detoxification of nitroaromatics towards methanogens can be expected to occur during anaerobic wastewater treatment. While the toxicity exerted by the N-substituted aromatic compounds was closely correlated with compound apolarity (log P), it was observed that at any given log P, N-substituted phenols had a toxicity that was 2 orders of magnitude higher than that of chlorophenols and alkylphenols. This indicates that toxicity due to the chemical reactivity of nitroaromatics is much more important than partitioning effects in bacterial membranes. 41 refs., 3 figs., 1 tab.« less

40 CFR 721.10023 - Benzenamine, N-phenyl-, ar ar′-(C9-rich C88-10-branched alkyl) derivs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenamine, N-phenyl-, ar arâ²-(C9... Significant New Uses for Specific Chemical Substances § 721.10023 Benzenamine, N-phenyl-, ar ar′-(C9-rich C88...) The chemical substance identified as benzenamine, N-phenyl-, ar,ar′-(C9-rich C8-10-branched alkyl...

Homogeneous synthesis of cellulose acrylate-g-poly (n-alkyl acrylate) solid-solid phase change materials via free radical polymerization.

PubMed

Qian, Yong-Qiang; Han, Na; Bo, Yi-Wen; Tan, Lin-Li; Zhang, Long-Fei; Zhang, Xing-Xiang

2018-08-01

A novel solid-solid phase change materials, namely, cellulose acrylate-g-poly (n-alkyl acrylate) (CA-g-PAn) (n = 14, 16 and 18) were successfully synthesized by free radical polymerization in N, N-dimethylacetamide (DMAc). The successful grafting was confirmed by fourier transform infrared spectra (FT-IR) and nuclear magnetic resonance (NMR). The properties of the CA-g-PAn copolymers were investigated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA). The phase change temperatures and the melting enthalpies of CA-g-PAn copolymers are in the range of 10.1-53.2 °C and 15-95 J/g, respectively. It can be adjusted by the contents of poly (n-alkyl acrylate) and the length of alkyl side-chain. The thermal resistant temperatures of CA-g-PA14, 16 and 18 copolymers are 308 °C, 292 °C and 273 °C, respectively. It show that all of grafting materials exhibit good thermal stability and shape stability. Therefore, it is expected to be applied in the cellulose-based thermos-regulating field. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthesis of 3-iodoindoles by the Pd/Cu-catalyzed coupling of N,N-dialkyl-2-iodoanilines and terminal acetylenes, followed by electrophilic cyclization.

PubMed

Yue, Dawei; Yao, Tuanli; Larock, Richard C

2006-01-06

[reaction: see text] 3-Iodoindoles have been prepared in excellent yields by coupling terminal acetylenes with N,N-dialkyl-o-iodoanilines in the presence of a Pd/Cu catalyst, followed by an electrophilic cyclization of the resulting N,N-dialkyl-o-(1-alkynyl)anilines using I2 in CH2Cl2. Aryl-, vinylic-, alkyl-, and silyl-substituted terminal acetylenes undergo this process to produce excellent yields of 3-iodoindoles. The reactivity of the carbon-nitrogen bond cleavage during cyclization follows the following order: Me > n-Bu, Me > Ph, and cyclohexyl > Me. Subsequent palladium-catalyzed Sonogashira, Suzuki, and Heck reactions of the resulting 3-iodoindoles proceed smoothly in good yields.

40 CFR 721.267 - N-[2-[(substituted dinitrophenyl)azo]diallylamino-4- substituted phenyl] acetamide (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.267 N-[2-[(substituted dinitrophenyl)azo]diallylamino-4- substituted phenyl] acetamide (generic name). (a) Chemical substance and...

A New Synthetic Route to N-Benzyl Carboxamides through the Reverse Reaction of N-Substituted Formamide Deformylase

PubMed Central

Hashimoto, Yoshiteru; Sakashita, Toshihide; Fukatsu, Hiroshi; Sato, Hiroyoshi

2014-01-01

Previously, we isolated a new enzyme, N-substituted formamide deformylase, that catalyzes the hydrolysis of N-substituted formamide to the corresponding amine and formate (H. Fukatsu, Y. Hashimoto, M. Goda, H. Higashibata, and M. Kobayashi, Proc. Natl. Acad. Sci. U. S. A. 101:13726–13731, 2004, doi:10.1073/pnas.0405082101). Here, we discovered that this enzyme catalyzed the reverse reaction, synthesizing N-benzylformamide (NBFA) from benzylamine and formate. The reverse reaction proceeded only in the presence of high substrate concentrations. The effects of pH and inhibitors on the reverse reaction were almost the same as those on the forward reaction, suggesting that the forward and reverse reactions are both catalyzed at the same catalytic site. Bisubstrate kinetic analysis using formate and benzylamine and dead-end inhibition studies using a benzylamine analogue, aniline, revealed that the reverse reaction of this enzyme proceeds via an ordered two-substrate, two-product (bi-bi) mechanism in which formate binds first to the enzyme active site, followed by benzylamine binding and the subsequent release of NBFA. To our knowledge, this is the first report of the reverse reaction of an amine-forming deformylase. Surprisingly, analysis of the substrate specificity for acids demonstrated that not only formate, but also acetate and propionate (namely, acids with numbers of carbon atoms ranging from C1 to C3), were active as acid substrates for the reverse reaction. Through this reaction, N-substituted carboxamides, such as NBFA, N-benzylacetamide, and N-benzylpropionamide, were synthesized from benzylamine and the corresponding acid substrates. PMID:24123742

Conformational preferences for some 2-substituted N-methoxy- N-methylacetamides through spectroscopic and theoretical studies

NASA Astrophysics Data System (ADS)

Olivato, Paulo R.; da Silva Gomes, Roberto; Rodrigues, Alessandro; Reis, Adriana K. C. A.; Domingues, Nelson L. C.; Rittner, Roberto; Dal Colle, Maurizio

2010-08-01

The analysis of the IR carbonyl band of the 2-substituted N-methoxy- N-methylacetamides Y-CH 2C(O)N(OMe)Me (Y = F 1, OMe 2, OPh 3, Cl 4), supported by B3LYP/6-311++G(3df, 3pd) calculations along with the NBO analysis for 1- 4, indicated the existence of cis- gauche conformers i.e. ( c) and ( g) for 1 and 3, ( c1,c2) and ( g1,g2) for 2, and ( c) and ( g1,g2) for 4. In the gas phase, the g conformer population prevails over the c one, for 1 and 3, the ( c1 + c2) population prevails over the ( g1 + g2) one for 2, and the ( g1 + g2) conformer population is more abundant than ( c) one for 4. In n-hexane solution, the cis conformer is more abundant for 1- 3. The occurrence of Fermi resonance in the νCO region, in n-hexane, precludes the estimative of relative populations of the ( c, g1, g2) conformers for 4. The SCI-PCM calculations agree with the solvent effect on the νCO band component relative intensities for 1- 3. NBO analysis showed that the nN → πco∗ orbital interaction is the main factor which stabilizes the gauche ( g, g1, g2) conformers for 1- 4 into a larger extent relative to the cis ( c, c1, c2) ones. The nY → πco∗, σCsbnd Y → πco∗, πco → σC sbnd Y ∗ and πco∗ → σC sbnd Y ∗ orbital interactions still contribute, but into a minor extent for the stabilization of the gauche conformers relative to the cis ones. The existence of some pyramidalization at the nitrogen atom of the Weinreb amides 1- 4 is responsible for the occurrence of Y δ-(4)···O δ-(9) and Y δ-(4)···N δ-(7) short contacts in the gauche ( g, g1, g2) conformers, which originates strong repulsive Coulombic interactions, acting in opposition to the large orbital stabilization of the gauche conformer with respect to the cis one. Therefore, a delicate balance of the Coulombic and orbital interactions seems to be responsible for the observed stabilization of the gauche ( g, g1, g2) and cis ( c, c1, c2) conformers, both in the gas phase and in the solution for 1- 4

Synthesis and evaluation of N-alkyl-beta-D-glucosylamines on the growth of two wood fungi, Coriolus versicolor and Poria placenta.

PubMed

Muhizi, Théoneste; Coma, Véronique; Grelier, Stéphane

2008-09-22

Various glucosylamines were synthesized from glucose and different alkyl amine compounds. These amino compounds are beta-D-glucopyranosylamine (GPA), N-ethyl-beta-D-glucopyranosylamine (EtGPA), N-butyl-beta-D-glucopyranosylamine (BuGPA), N-hexyl-beta-D-glucopyranosylamine (HeGPA), N-octyl-beta-D-glucopyranosylamine (OcGPA), N-dodecyl-beta-D-glucopyranosylamine (DoGPA), N-(2-hydroxyethyl)-beta-D-glucopyranosylamine (HEtGPA) and N,N-di(2-hydroxyethyl)-beta-D-glucopyranosylamine (DHEtGPA). They were tested for their antifungal activity against the growth of Coriolus versicolor and Poria placenta. An improvement of the antifungal activity with the increase of alkyl chain length was observed. DoGPA exhibited the best antifungal activity against both strains. It completely inhibited the fungal growth at 0.01x10(-3)molmL(-1) and 0.0075x10(-3)molmL(-1) for C. versicolor and P. placenta, respectively. For other glucosylamines higher concentrations were needed for complete inhibition of fungi.

Dielectric relaxation of alkyl chains in graphite oxide and n-alkylammonium halides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ai, Xiaoqian; Tian, Yuchen; Gu, Min, E-mail: mgu@nju.edu.cn

2016-05-15

The dynamic of n-alkylammonium halides and n-alkylammonium cations (n = 12, 14, 16, 18) intercalated in graphite oxide (GO) have been investigated with complex impedance spectroscopy. X-ray diffraction, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, elemental analysis and thermogravimetry served to characterize the materials. The intercalated alkylammonium cations distributes as monolayers (when n = 12, 14 or 16) or bilayers (when n = 18), with their long axis parallel to GO layers, and with cations of headgroups bonded ionically to C-O{sup -} groups of GO; backbones of the confined molecules remain free. All halides and intercalation compounds suffer dielectric loss atmore » low temperature. Arrhenius plots of the thermal dependence of the loss peaks, which are asymmetric, produce apparent activation energies that rise with increasing n. Ngai’s correlated-state model helps to correct for effects of dipole-dipole interaction, leading to virtually identical values for actual activation energy of 110 meV ± 5%; the values are also almost the same as the barrier energy for internal rotation in the alkyl macromolecule. We conclude that the relaxation of the alkylammonium cations arises not from C{sub 3} reorientation of the CH{sub 3} at its headgroup, but from small-angle wobbling around its major axis, an intrinsic motion.« less

Spectroscopic and structural characterization of the charge-transfer interaction of N,N'-bis-alkyl derivatives of 1,4,6,8-naphthalenediimide with chloranilic and picric acids.

PubMed

Refat, Moamen S; Ahmed, Hamdy A; Grabchev, Ivo; El-Zayat, Lamia A

2008-09-01

Charge-transfer (CT) complexes formed from the reactions of two N,N'-bis-alkyl derivatives of 1,4,6,8-naphthalenediimide such as N,N'-bis[2-hydroxyethyl)]-1,4,6,8-naphthalenediimide (BHENDI) and N,N'-bis-[2-N,N-dimethylaminoethyl)]-1,4,6,8-naphthalenediimide (BDMAENDI) with chloranilic acid (CLA) and piciric acid (PA) as pi-acceptors, have been studied spectrophotometrically in methanol and chloroform, respectively at 25 degrees C. The photometric titration curves for the reactions indicated that the data obtained refer to 1:1 charge-transfer complexes of [(BHENDI)(CLA)], [(BDMAENDI)(CLA)], [(BHENDI)(PA)] and [(BDMAENDI)(PA)] were formed. Benesi-Hildebrand and its modification methods were applied to the determination of association constant (K), molar extinction coefficient (epsilon). The solid CT complexes have been synthesized and characterization by different spectral methods.

Spectroscopic and structural characterization of the charge-transfer interaction of N,N'-bis-alkyl derivatives of 1,4,6,8-naphthalenediimide with chloranilic and picric acids

NASA Astrophysics Data System (ADS)

Refat, Moamen S.; Ahmed, Hamdy A.; Grabchev, Ivo; El-Zayat, Lamia A.

2008-09-01

Charge-transfer (CT) complexes formed from the reactions of two N,N'-bis-alkyl derivatives of 1,4,6,8-naphthalenediimide such as N, N'-bis[2-hydroxyethyl)]-1,4,6,8-naphthalenediimide (BHENDI) and N, N'-bis-[2- N, N-dimethylaminoethyl)]-1,4,6,8-naphthalenediimide (BDMAENDI) with chloranilic acid (CLA) and piciric acid (PA) as π-acceptors, have been studied spectrophotometrically in methanol and chloroform, respectively at 25 °C. The photometric titration curves for the reactions indicated that the data obtained refer to 1:1 charge-transfer complexes of [(BHENDI)(CLA)], [(BDMAENDI)(CLA)], [(BHENDI)(PA)] and [(BDMAENDI)(PA)] were formed. Benesi-Hildebrand and its modification methods were applied to the determination of association constant ( K), molar extinction coefficient ( ɛ). The solid CT complexes have been synthesized and characterization by different spectral methods.

Reassessment of structure of smectic phases: Nano-segregation in smectic E phase in 4-n-alkyl-4'-isothiocyanato-1,1'-biphenyls

NASA Astrophysics Data System (ADS)

Saito, Kazuya; Miyazawa, Takahito; Fujiwara, Akio; Hishida, Mafumi; Saitoh, Hideki; Massalska-Arodź, Maria; Yamamura, Yasuhisa

2013-09-01

Based on new diffraction data from aligned samples of smectic E (SmE) phase of 4-n-alkyl-4'-isothiocyanato-1,1'-biphenyls, systematics against the alkyl chain length n is analyzed. In order to perform the analysis, the molecular form factor approximated by a box-shaped distribution is calculated while taking the rounding of the distribution at corners into account. The analysis clearly shows the nano-segregated layered structure, which does not fit to the traditional structural view of SmE phase but does fit to the model the present authors proposed recently. Some implications of this conclusion are discussed in relation to the importance of the molten state of alkyl chains in most of real mesogens revealed previously through thermodynamic analyses.

Iridium-catalyzed direct synthesis of tryptamine derivatives from indoles: exploiting n-protected β-amino alcohols as alkylating agents.

PubMed

Bartolucci, Silvia; Mari, Michele; Bedini, Annalida; Piersanti, Giovanni; Spadoni, Gilberto

2015-03-20

The selective C3-alkylation of indoles with N-protected ethanolamines involving the "borrowing hydrogen" strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.

N-iodoacetyltyramine: Preparation and use in sup 125 I labeling by alkylation of sulfhydryl groups

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, C.M.; Mihal, K.A.; Krueger, R.J.

1989-06-01

Preparation and use of N-iodoacetyltyramine in generation of {sup 125}I-labeled compounds is described. The kinetics of alkylation of N-acetylcysteine by N-iodoacetyltyramine (k2 = 3.0 M-1 s-1) and N-chloroacetyltyramine (k2 = 0.12 M-1 s-1) indicate that N-iodoacetyltyramine is more useful for labeling sulfhydryl-containing compounds to high specific activity with {sup 125}I. Conditions for preparation of carrier-free {sup 125}I-labeled N-iodoacetyl-3-monoiodotyramine in 50% yield based on starting iodide are described. The high degree of group specificity of N-iodoacetyl-3-monoiodotyramine reaction with sulfhydryl groups is demonstrated by the high reactivity toward sulfhydryl-containing bovine serum albumin and low reactivity toward N-ethylmaleimide-blocked bovine serum albumin and IgG.more » {sup 125}I-labeled N-iodoacetyl-3-monoiodotyramine was also used to prepare an {sup 125}I-labeled ACTH derivative that retains full biological activity, further demonstrating the selectivity toward reactions with sulfhydryl groups.« less

Mechanistic Studies of para-Substituted N,N'-Dibenzyl-1,4-diaminobutanes as Substrates for a Mammalian Polyamine Oxidase

PubMed Central

Pozzi, Michelle Henderson; Gawandi, Vijay; Fitzpatrick, Paul F.

2009-01-01

The kinetics of oxidation of a series of para-substituted N, N'-dibenzyl-1,4-diaminobutanes by the flavoprotein polyamine oxidase from mouse have been determined to gain insight into the mechanism of amine oxidation by this member of the monoamine oxidase structural family. The kcat/Km values are maximal at pH 9, consistent with the singly charged substrate being the active form. The rate constant for flavin reduction, kred, by N,N'-dibenzyl-1,4-diaminobutane decreases about 5-fold below a pKa of ~8; this is attributed to the need for a neutral nitrogen at the site of oxidation. The kred and kcat values are comparable for each of the N, N'-dibenzyl-1,4-diaminobutanes, consistent with rate-limiting reduction. The deuterium kinetic isotope effects on kred and kcat are identical for each of the N, N'-dibenzyl-1,4-diaminobutanes, consistent with rate-limiting cleavage of the substrate CH bond. The kred values for seven different para-substituted N, N'-dibenzyl-1,4-diaminobutanes correlate with a combination of the van der Waals volume and σ value of the substrates, with ρ values of −0.59 at pH 8.6 and −0.09 at pH 6.6. These results are consistent with direct transfer of a hydride from the neutral CN bond of the substrate to the flavin as the mechanism of polyamine oxidase. PMID:19911805

Transamination at the Crossroad of the One-Pot Synthesis of N-Substituted Quinonediimines and C-Substituted Benzobisimidazoles.

PubMed

Andeme Edzang, Judicaelle; Chen, Zhongrui; Audi, Hassib; Canard, Gabriel; Siri, Olivier

2016-10-10

A green and very efficient synthesis of N-substituted benzoquinonediimines or C-substituted benzo-bis(imidazole) derivatives is described under similar conditions. The different reaction pathway is only controlled by the nature of the primary amines, which tunes the reactivity of the intermediates.

Transient alkylaminium radicals in n-hexane. Condensed-phase ion-molecule reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werst, D.W.; Trifunac, A.D.

Time-resolved fluorescence detected magnetic resonance (FDMR) is used to observe alkylaminium radicals formed in n-hexane solutions by electron pulse radiolysis. The ease of observation of aminium radical FDMR signals increases with increasing alkyl substitution of the amine solutes. The results are discussed in terms of the ion-molecule reactions, such as proton transfer, which compete with the electron-transfer processes, i.e, the electron transfer from solute molecules to n-hexane radical cations and geminate recombination.

Intramolecular Diels-Alder Reaction of N-Alkyl-2-cyano-1-azadienes: A Study of the Eschenmoser Cycloreversion of Dihydrooxazines as a Route to N-Alkyl-2-cyano-1-azadienes.

PubMed

Motorina, Irina A.; Fowler, Frank W.; Grierson, David S.

1997-04-04

In connection with the development of the intramolecular Diels-Alder reaction (IMDA) of 1-azadienes, the 5,6-dihydro-4H-1,2-oxazine 12has been evaluated as a synthon equivalent of the 2-cyano-1-azadiene system. It was found that the dihydrooxazonium salt 27, generated in situ from the cyclic hydroxamic acid derivative 26, is converted directly to azadiene 4a via tautomerization to the corresponding enamine and a particularly facile Eschenmoser type cycloreversion process. Conditions were subsequently found for the preparation of synthon 12. N-Alkylation of this intermediate with alkyl bromides in the presence of Ag(+) ion also resulted in direct formation of the 2-cyano-1-azadiene products 38a-dand 4a. Microwave irradiation of a benzene solution of azadiene 4a proved to be a convenient means to effect its IMDA conversion to indolizidine 5a. To avoid decomposition of azadiene 38c, its intramolecular cycloaddition giving 40 (60%) was achieved by flash vacuum thermolysis.

pi-Selective stationary phases: (II) Adsorption behavior of substituted aromatic compounds on n-alkyl-phenyl stationary phases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gritti, Fabrice; Guiochon, Georges A; Mayfield, Kirsty

2010-01-01

The frontal analysis method was used to measure the adsorption isotherms of phenol, 4-chlorophenol, p-cresol, 4-methoxyphenol and caffeine on a series of columns packed with home-made alkyl-phenyl bonded silica particles. These ligands consist of a phenyl ring tethered to the silica support via a carbon chain of length ranging from 0 to 4 atoms. The adsorption isotherm models that fit best to the data account for solute-solute interactions that are likely caused by p-p interactions occurring between aromatic compounds and the phenyl group of the ligand. These interactions are the dominant factor responsible for the separation of low molecular weightmore » aromatic compounds on these phenyl-type stationary phases. The saturation capacities depend on whether the spacer of the ligands have an even or an odd number of carbon atoms, with the even alkyl chain lengths having a greater saturation capacity than the odd alkyl chain lengths. The trends in the adsorption equilibrium constant are also significantly different for the even and the odd chain length ligands.« less

Design, synthesis and preliminary antimicrobial evaluation of n-alkyl chain tethered c-5 functionalized bis-isatins

USDA-ARS?s Scientific Manuscript database

A series of N-alkyl tethered C-5 functionalized bis-isatins were synthesized and evaluated for antimicrobial activity against pathogenic microorganisms. The preliminary evaluation studies revealed the compound 4t, with an optimal combination of bromo-substituent at the C-5 position of isatin ring al...

The Novel Bacterial N-Demethylase PdmAB Is Responsible for the Initial Step of N,N-Dimethyl-Substituted Phenylurea Herbicide Degradation

PubMed Central

Gu, Tao; Zhou, Chaoyang; Sørensen, Sebastian R.; Zhang, Ji; He, Jian; Yu, Peiwen; Li, Shunpeng

2013-01-01

The environmental fate of phenylurea herbicides has received considerable attention in recent decades. The microbial metabolism of N,N-dimethyl-substituted phenylurea herbicides can generally be initiated by mono-N-demethylation. In this study, the molecular basis for this process was revealed. The pdmAB genes in Sphingobium sp. strain YBL2 were shown to be responsible for the initial mono-N-demethylation of commonly used N,N-dimethyl-substituted phenylurea herbicides. PdmAB is the oxygenase component of a bacterial Rieske non-heme iron oxygenase (RO) system. The genes pdmAB, encoding the α subunit PdmA and the β subunit PdmB, are organized in a transposable element flanked by two direct repeats of an insertion element resembling ISRh1. Furthermore, this transposable element is highly conserved among phenylurea herbicide-degrading sphingomonads originating from different areas of the world. However, there was no evidence of a gene for an electron carrier (a ferredoxin or a reductase) located in the immediate vicinity of pdmAB. Without its cognate electron transport components, expression of PdmAB in Escherichia coli, Pseudomonas putida, and other sphingomonads resulted in a functional enzyme. Moreover, coexpression of a putative [3Fe-4S]-type ferredoxin from Sphingomonas sp. strain RW1 greatly enhanced the catalytic activity of PdmAB in E. coli. These data suggested that PdmAB has a low specificity for electron transport components and that its optimal ferredoxin may be the [3Fe-4S] type. PdmA exhibited low homology to the α subunits of previously characterized ROs (less than 37% identity) and did not cluster with the RO group involved in O- or N-demethylation reactions, indicating that PdmAB is a distinct bacterial RO N-demethylase. PMID:24123738

Globular, Sponge-like to Layer-like Morphological Transition in 1-n-Alkyl-3-methylimidazolium Octylsulfate Ionic Liquid Homologous Series.

PubMed

Kapoor, Utkarsh; Shah, Jindal K

2018-01-11

Segregation of polar and nonpolar domains in ionic liquids for which either the cation or anion is responsible for inducing nonpolar domains is well understood. On the other hand, information regarding the nanoscale heterogeneities originating due to the presence of nonpolar content on both the ions is rudimentary at this point. The present contribution is aimed at addressing this question and focuses on a molecular dynamics simulation study to probe nanoscale structural and aggregation features of the 1-n-alkyl-3-methylimidazolium [C n mim] octylsulfate [C 8 SO 4 ] ionic liquid homologous series (n = 2, 4, 6, 8, 10, and 12). The objective of this work is to determine the effect of increasing alkyl chain length in the cation on nonpolar domain formation, especially when the alkyl chain lengths from both the ions participate in defining such domains. The results indicate that all the ionic liquids form nonpolar domains, morphology of which gradually changes from globular, sponge-like to layer-like structure with increase in the cationic alkyl chain length. The length of the nonpolar domains calculated from the total structure factor for [C 10 mim][C 8 SO 4 ] is considerably higher than that reported for other imidazolium-based ionic liquid containing smaller anions. The structure factor for [C 12 mim][C 8 SO 4 ] ionic liquid contains multiple intermediate peaks separating the charge alternation peak and pre-peak, which points to nonpolar domains of varying lengths, an observation that remains to be validated. Analysis of the heterogeneous order parameters and orientational correlation functions of the alkyl chains further suggests an increase in the spatial heterogeneity and long-range order along the homologous series. The origin of rich diversity of structures obtained by introducing nonpolar content on both the ions is discussed.

Singlet Fission and Excimer Formation in Disordered Solids of Alkyl-Substituted 1,3-Diphenylisobenzofurans

DOE PAGES

Dron, Paul I.; Michl, Josef; Johnson, Justin C.

2017-10-16

Here, we describe the preparation and excited state dynamics of three alkyl derivatives of 1,3-diphenylisobenzofuran (1) in both solutions and thin films. The substitutions are intended to disrupt the slip-stacked packing observed in crystals of 1 while maintaining the favorable energies of singlet and triplet for singlet fission (SF). All substitutions result in films that are largely amorphous as judged by the absence of strong X-ray diffraction peaks.

S - and N-alkylating agents diminish the fluorescence of fluorescent dye-stained DNA.

PubMed

Giesche, Robert; John, Harald; Kehe, Kai; Schmidt, Annette; Popp, Tanja; Balzuweit, Frank; Thiermann, Horst; Gudermann, Thomas; Steinritz, Dirk

2017-01-25

Sulfur mustard (SM), a chemical warfare agent, causes DNA alkylation, which is believed to be the main cause of its toxicity. SM DNA adducts are commonly used to verify exposure to this vesicant. However, the required analytical state-of-the-art mass-spectrometry methods are complex, use delicate instruments, are not mobile, and require laboratory infrastructure that is most likely not available in conflict zones. Attempts have thus been made to develop rapid detection methods that can be used in the field. The analysis of SM DNA adducts (HETE-G) by immunodetection is a convenient and suitable method. For a diagnostic assessment, HETE-G levels must be determined in relation to the total DNA in the sample. Total DNA can be easily visualized by the use of fluorescent DNA dyes. This study examines whether SM and related compounds affect total DNA staining, an issue that has not been investigated before. After pure DNA was extracted from human keratinocytes (HaCaT cells), DNA was exposed to different S- and N-alkylating agents. Our experiments revealed a significant, dose-dependent decrease in the fluorescence signal of fluorescent dye-stained DNA after exposure to alkylating agents. After mass spectrometry and additional fluorescence measurements ruled out covalent modifications of ethidium bromide (EthBr) by SM, we assumed that DNA crosslinks caused DNA condensation and thereby impaired access of the fluorescent dyes to the DNA. DNA digestion by restriction enzymes restored fluorescence, a fact that strengthened our hypothesis. However, monofunctional agents, which are unable to crosslink DNA, also decreased the fluorescence signal. In subsequent experiments, we demonstrated that protons produced during DNA alkylation caused a pH decrease that was found responsible for the reduction in fluorescence. The use of an appropriate buffer system eliminated the adverse effect of alkylating agents on DNA staining with fluorescent dyes. An appropriate buffer system is thus

1,7-Bis-(N,N-dialkylamino)perylene Bisimides: Facile Synthesis and Characterization as Near-Infrared Fluorescent Dyes

PubMed Central

Chen, Kew-Yu; Chang, Che-Wei

2014-01-01

Three symmetric alkylamino-substituted perylene bisimides with different n-alkyl chain lengths (n = 6, 12, or 18), 1,7-bis-(N,N-dialkylamino)perylene bisimides (1a–1c), were synthesized under mild condition and were characterized by 1H NMR, 13C NMR and high resolution mass spectroscopy. Their optical and electrochemical properties were measured using UV-Vis and emission spectroscopic techniques as well as cyclic voltammetry (CV). These compounds show deep green color in both solution and solid state, and are highly soluble in dichloromethane and even in nonpolar solvents such as hexane. The shapes of the absorption spectra of 1a–1c in the solution and solid state were found to be almost the same, indicating that the long alkyl chains could efficiently prevent intermolecular contact and aggregation. They show a unique charge transfer emission in the near-infrared region, of which the peak wavelengths exhibit strong solvatochromism. The dipole moments of the molecules have been estimated using the Lippert–Mataga equation, and upon excitation, they show larger dipole moment changes than that of 1,7-diaminoperylene bisimide (2). Moreover, all the dyes exhibit two irreversible one-electron oxidations and two quasi-reversible one-electron reductions in dichloromethane at modest potentials. Complementary density functional theory calculations performed on these chromophores are reported in order to rationalize their electronic structure and optical properties. PMID:28788262

Rh-Catalyzed Annulations of N-Methoxybenzamides and Ketenimines: Sterically and Electronically Controlled Synthesis of Isoquinolinones and Isoindolinones.

PubMed

Zhou, Xiaorong; Zhang, Zhiyin; Zhao, Hongyang; Lu, Ping; Wang, Yanguang

2017-04-07

Rhodium-catalyzed C-H activation/annulation reactions of ketenimines with N-methoxybenzamides are reported. The outcome of reactions is dependent on the structure of ketenimines. The β-alkyl-substituted ketenimines furnish 3-iminoisoquinolin-1(2H)-ones in a formal [4 + 2] annulation manner, while the β-ester substituted ketenimines afford 3-aminoisoindolin-1-ones in a formal [4 + 1] annulation manner. The synthesized [4 + 2] products undergo an intramolecular Cu-catalyzed C-N coupling to be converted to benzo[4,5]imidazo[1,2-b]isoquinolin-11-ones, which can be directly prepared from ketenimines and N-methoxybenzamides by a one-pot Rh-catalyzed annulation/Cu-catalyzed C-N coupling sequence.

N-alkylated aminopyrazines for use as hydrophilic optical agents

NASA Astrophysics Data System (ADS)

Poreddy, Amruta R.; Asmelash, Bethel; Galen, Karen P.; Fitch, Richard M.; Shieh, Jeng-Jong; Wilcox, James M.; Schoenstein, Tasha M.; Wojdyla, Jolette K.; Gaston, Kimberly R.; Freskos, John N.; Neumann, William L.; Rajagopalan, Raghavan; Ahn, Hyo-Yang; Kostelc, James G.; Debreczeny, Martin P.; Belfield, Kevin D.; Dorshow, Richard B.

2009-02-01

Rapid assessment of glomerular filtration rate (GFR), which measures the amount of plasma filtered through the kidney within a given time, would greatly facilitate monitoring of renal function for patients at the bedside in the clinic. In our pursuit to develop exogenous fluorescent tracers for real-time monitoring of renal function by optical methods, N-alkylated aminopyrazine dyes and their hydrophilic conjugates based on poly (ethylene glycol) (PEG) were synthesized via reductive amination as the key step. Photophysical properties indicated a bathochromic shift on the order of 50 nm in both absorption and emission compared to naked aminopyrazines which could be very useful in enhancing both tissue penetration as well as easier detection methods. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies, and the correlation of in vivo optical data with plasma PK for measurement of clearance (and hence GFR) are focus of the current investigation.

Alkyl nitrate formation from the reactions of C8-C14 n-alkanes with OH radicals in the presence of NO(x): measured yields with essential corrections for gas-wall partitioning.

PubMed

Yeh, Geoffrey K; Ziemann, Paul J

2014-09-18

In this study, C8-C14 n-alkanes were reacted with OH radicals in the presence of NO(x) in a Teflon film environmental chamber and isomer-specific yields of alkyl nitrates were determined using gas chromatography. Because results indicated significant losses of alkyl nitrates to chamber walls, gas-wall partitioning was investigated by monitoring the concentrations of a suite of synthesized alkyl nitrates added to the chamber. Gas-to-wall partitioning increased with increasing carbon number and with proximity of the nitrooxy group to the terminal carbon, with losses as high as 86%. The results were used to develop a structure-activity model to predict the effects of carbon number and isomer structure on gas-wall partitioning, which was used to correct the measured yields of alkyl nitrate isomers formed in chamber reactions. The resulting branching ratios for formation of secondary alkyl nitrates were similar for all isomers of a particular carbon number, and average values, which were almost identical to alkyl nitrate yields, were 0.219, 0.206, 0.254, 0.291, and 0.315 for reactions of n-octane, n-decane, n-dodecane, n-tridecane, and n-tetradecane, respectively. The increase in average branching ratios and alkyl nitrate yields with increasing carbon number to a plateau value of ∼0.30 at about C13-C14 is consistent with predictions of a previously developed model, indicating that the model is valid for alkane carbon numbers ≥C3.

Absence of S[subscript N]1 Involvement in the Solvolysis of Secondary Alkyl Compounds

ERIC Educational Resources Information Center

Murphy, Thomas J.

2009-01-01

There are significant contradictions in undergraduate organic chemistry textbooks as to the mechanism of nucleophilic substitution reactions at saturated secondary carbons. Some texts say that only the S[subscript N]2 mechanism operates, others say that solvolysis reactions go entirely by the S[subscript N]1 mechanism, while most texts say that…

Computational insights into crystal plane dependence of thermal activity of anion (C and N)-substituted titania.

PubMed

V, Sai Phani Kumar; Arya, Rahul; Deshpande, Parag A

2017-11-29

Geometry optimizations of anion (C and N) doped anatase TiO 2 were carried out by using DFT+U calculations. Various anion vacancy sites were examined to study the synergistic effects of anion doping accompanied with anion vacancy formation on lattice oxygen activation. Two non-identical crystal planes (0 0 1) and (1 0 0) were chosen for C and N substitutions. Energetically favoured N-vacancy pairs were identified on TiO 2 surfaces. Substitution of N along with anion vacancies at various sites was energetically more favoured than that of C-doping in bulk TiO 2 while the energies were comparable for surface substitutions. Bond length distributions due to the formation of differential bonds were determined. Net oxygen activation and accompanying reversible oxygen exchange capacities were compared for TiO 2-2x C x and TiO 2-3x N 2x . Substitution of C in the surface exposed (1 0 0) plane of TiO 2 resulted in 47.6% and 23.8% of bond elongation and compression, respectively, resulting in 23.8% of net oxygen activation which was higher when compared to N substitution in the (1 0 0) plane of TiO 2 resulting in a net oxygen activation of 17%.

Metal-Free Functionalization of N,N-Dialkylanilines via Temporary Oxidation to N,N-Dialkylaniline N-Oxides and Group Transfer

PubMed Central

2015-01-01

A simple set of protocols for the controlled elaboration of anilines is reported allowing access to a diverse array of aminophenols, aminoarylsulfonates, alkylated anilines, and aminoanilines in 29–95% yield in a single laboratory operation from easily isolable, bench-stable N,N-dialkylaniline N-oxides. The introduction of new C–O, C–C, and C–N bonds on the aromatic ring is made possible by a temporary increase in oxidation level and excision of a weak N–O bond. PMID:24992642

Volatilization of benzene and eight alkyl-substituted benzene compounds from water

USGS Publications Warehouse

Rathbun, R.E.; Tai, D.Y.

1988-01-01

Predicting the fate of organic compounds in streams and rivers often requires knowledge of the volatilization characteristics of the compounds. The reference-substance concept, involving laboratory-determined ratios of the liquid-film coefficients for volatilization of the organic compounds to the liquid-film coefficient for oxygen absorption, is used to predict liquid-film coefficients for streams and rivers. In the absence of experimental data, two procedures have been used for estimating these liquid-film coefficient ratios. These procedures, based on the molecular-diffusion coefficient and on the molecular weight, have been widely used but never extensively evaluated. Liquid-film coefficients for the volatilization of benzene and eight alkyl-substituted benzene compounds (toluene through n-octylbenzene) from water were measured in a constant-temperature, stirred water bath. Liquid-film coefficients for oxygen absorption were measured simultaneously. A range of water mixing conditions was used with a water temperature of 298.2 K. The ratios of the liquid-film coefficients for volatilization to the liquid-film coefficient for oxygen absorption for all of the organic compounds were independent of mixing conditions in the water. Experimental ratios ranged from 0.606 for benzene to 0.357 for n-octylbenzene. The molecular-diffusion-coefficient procedure accurately predicted the ratios for ethylbenzene through n-pentylbenzene with a power dependence of 0.566 on the molecular-diffusion coefficient, in agreement with published values. Predicted ratios for benzene and toluene were slightly larger than the experimental ratios. These differences were attributed to possible interactions between the molecules of these compounds and the water molecules and to benzene-benzene interactions that form dimers. Because these interactions also are likely to occur in natural waters, it was concluded that the experimental ratios are more correct than the predicted ratios for

Gold-catalyzed and N-iodosuccinimide-mediated cyclization of gamma-substituted allenamides.

PubMed

Hyland, Christopher J T; Hegedus, Louis S

2006-10-27

Chiral gamma-substituted allenamides have been shown to undergo efficient gold-catalyzed and N-iodosuccinimide-mediated cyclization to highly functionalized dihydrofurans. These reactions proceed rapidly and without loss of stereochemistry.

Specific interactions study in complexes of poly(mono-n-alkyl itaconates) with tertiary polyamides.

PubMed

Katime, Issa; Meaurio, Emilio; Cesteros, Luis C; Mendizábal, Eduardo

2003-07-01

This paper reports an FT-IR study of blends of poly(mono-n-alkyl itaconates) with poly(N,N-dimethylacrylamide) (PDMA) and poly(ethyloxazoline) (PEOX). Strong hydrogen bonding has been found, and both polybases have shown similar acceptor strengths. Derivative techniques show asymmetric profiles for the free carbonyl band of the polybases, resulting in shifted band locations. The extent of the interassociation has been estimated by spectral curve fitting of the polybase carbonyl band. The results show that the interaction degree in blends with PEOX does not depend on the length of the poly(monoalkyl itaconate) side group, while an inter-associating ability loss is observed in blends with PDMA as the side-group size of the polyacid increases. This different behavior is attributed to the greater interspacing between vicinal carbonyl groups in PEOX. This band shows conformational sensitivity and reflects the conformational changes that occur as the steric hindrances present in the medium (due to the bulky side groups of the polyacids) increase.

Design synthesis and structure-activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)propionamide derivatives as opioid ligands.

PubMed

Deekonda, Srinivas; Rankin, David; Davis, Peg; Lai, Josephine; Vanderah, Todd W; Porecca, Frank; Hruby, Victor J

2016-01-15

Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl)methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850-4 nM) and were selective towards the μ opioid receptor over the δ opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the μ opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75±21 nM, and 190±42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170±42 nM, in contrast to its binding affinity results. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis and evaluation of novel N-H and N-substituted indole-2- and 3-carboxamide derivatives as antioxidants agents.

PubMed

Olgen, Süreyya; Kiliç, Zuhal; Ada, Ahmet O; Coban, Tulay

2007-08-01

We have previously reported on the synthesis of novel indole derivatives where some compounds showed significant antioxidant activity. Here, we report the synthesis of novel N-H and N-substituted indole-2- and 3-carboxamide derivatives and investigated their antioxidant role in order to identify structural characteristics responsible for activity. Although all compounds showed a strong inhibitory (95-100%) effect on superoxide anion (SOD) only compounds 4, 5 and 6 showed simliar potency for the inhibition of lipid peroxidation (81-94%) which revealed that compounds 4, 5 and 6 possessed highly potent antioxidant properties. Substitution in the 1-position of the indole ring caused the significant differences between the activity results regarding lipid peroxidation inhibition.

The formation of quasi-alicyclic rings in alkyl-aromatic compounds

NASA Astrophysics Data System (ADS)

Straka, Pavel; Buryan, Petr; Bičáková, Olga

2018-02-01

The alkyl side chains of n-alkyl phenols, n-alkyl benzenes and n-alkyl naphthalenes are cyclised, as demonstrated by GC measurements, FTIR spectroscopy and molecular mechanics calculations. Cyclisation occurs due to the intramolecular interaction between an aromatic ring (-δ) and a hydrogen of the terminal methyl group (+δ) of an alkyl chain. In fact, conventional molecules are not aliphatic-aromatic, but quasi-alicyclic-aromatic. With the aromatic molecules formed with a quasi-alicyclic ring, the effect of van der Waals attractive forces increases not only intramolecularly but also intermolecularly. This effect is strong in molecules with propyl and higher alkyl substituents. The increase of intermolecular van der Waals attractive forces results in bi-linearity in the GC retention time of the compounds in question, observed in the dependence of the logarithm of the relative retention time on the number of carbons in a molecule in both polar and nonpolar stationary phases with both capillary and packed columns. The role of van der Waals forces has been demonstrated using the potential energies of covalent and noncovalent interactions for 2-n-alkyl phenols, n-alkyl benzenes and 1-n-alkyl- and 2-n-alkyl naphthalenes.

Photochemical Reactions of (n(5)-Pentamethylcyclpentadienyl)-Dicarbonyliron-Alkyl and -Silyl Complexes: Reversible Ethylene Insertion into an Iron-Silicon Bond and Implications for the Mechanism of Transition Metal-Catalyzed Hydrosilation of Alkenes.

DTIC Science & Technology

1985-12-11

RD-R162 462 PHOTOCHEMICAL REACTIONS OF(N(S)-P NTANETNYLCVCLPENTADIENYL)-DICARRONVLIR.. (U) MASSACHUSETTS INST OF TECH CAMBRIDGE DEPT OF CHEMISTRY...34 Photochemical Reactions of (n5-Pentamethylcyclpentadienyl)- Dicarbonyliron-Alkyl and -Silyl Complexes: Reversible Ethylene Insertion into an Iron-Silicon Bond...Chemical Society) PHOTOCHEMICAL REACTIONS OF (n5-PENTAMETHYLCYCLOPENTADIENYL)- DICARBONYLIRON-ALKYL AND -SILYL COMPLEXES: REVERSIBLE ETHYLENE INSERTION INTO

Why Does Alkylation of the N-H Functionality within M/NH Bifunctional Noyori-Type Catalysts Lead to Turnover?

PubMed

Dub, Pavel A; Scott, Brian L; Gordon, John C

2017-01-25

Molecular metal/NH bifunctional Noyori-type catalysts are remarkable in that they are among the most efficient artificial catalysts developed to date for the hydrogenation of carbonyl functionalities (loadings up to ∼10 -5 mol %). In addition, these catalysts typically exhibit high C═O/C═C chemo- and enantioselectivities. This unique set of properties is traditionally associated with the operation of an unconventional mechanism for homogeneous catalysts in which the chelating ligand plays a key role in facilitating the catalytic reaction and enabling the aforementioned selectivities by delivering/accepting a proton (H + ) via its N-H bond cleavage/formation. A recently revised mechanism of the Noyori hydrogenation reaction (Dub, P. A. et al. J. Am. Chem. Soc. 2014, 136, 3505) suggests that the N-H bond is not cleaved but serves to stabilize the turnover-determining transition states (TDTSs) via strong N-H···O hydrogen-bonding interactions (HBIs). The present paper shows that this is consistent with the largely ignored experimental fact that alkylation of the N-H functionality within M/NH bifunctional Noyori-type catalysts leads to detrimental catalytic activity. The purpose of this work is to demonstrate that decreasing the strength of this HBI, ultimately to the limit of its complete absence, are conditions under which the same alkylation may lead to beneficial catalytic activity.

INTERLABORATORY STUDY OF A THERMOSPRAY-LIQUID CHROMATOGRAPHIC/MASS SPECTROMETRIC METHOD FOR SELECTED N-METHYL CARBAMATES, N-METHYL CARBAMOYLOXIMES, AND SUBSTITUTED UREA PESTICIDES

EPA Science Inventory

A thermospray-liquid chromatographic/mass spectrometric (TS-LC/MS) method was evaluated in an interlaboratory study for determining 3 N-methyl carbamates (bendiocarb, carbaryl, and carbofuran), 3-N-methyl carbamoyloximes (aldicarb, methomyl, and oxamyl), 2 substituted urea pestic...

Improving p-type doping efficiency in Al0.83Ga0.17N alloy substituted by nanoscale (AlN)5/(GaN)1 superlattice with MgGa-ON δ-codoping: Role of O-atom in GaN monolayer

NASA Astrophysics Data System (ADS)

Zhong, Hong-xia; Shi, Jun-jie; Zhang, Min; Jiang, Xin-he; Huang, Pu; Ding, Yi-min

2015-01-01

We calculate Mg-acceptor activation energy EA and investigate the influence of O-atom, occupied the Mg nearest-neighbor, on EA in nanoscale (AlN)5/(GaN)1 superlattice (SL), a substitution for Al0.83Ga0.17N disorder alloy, using first-principles calculations. We find that the N-atom bonded with Ga-atom is more easily substituted by O-atom and nMgGa-ON (n = 1-3) complexes are favorable and stable in the SL. The O-atom plays a dominant role in reducing EA. The shorter the Mg-O bond is, the smaller the EA is. The Mg-acceptor activation energy can be reduced significantly by nMgGa-ON δ-codoping. Our calculated EA for 2MgGa-ON is 0.21 eV, and can be further reduced to 0.13 eV for 3MgGa-ON, which results in a high hole concentration in the order of 1020 cm-3 at room temperature in (AlN)5/(GaN)1 SL. Our results prove that nMgGa-ON (n = 2,3) δ-codoping in AlN/GaN SL with ultrathin GaN-layer is an effective way to improve p-type doping efficiency in Al-rich AlGaN.

Substitution of the nitro group with Grignard reagents: facile arylation and alkenylation of pyridine N-oxides.

PubMed

Zhang, Fang; Zhang, Song; Duan, Xin-Fang

2012-11-02

The unprecedented substitution of a nitro group with aryl or alkenyl groups of Grignard reagents affords 2-aryl or alkenylpyridine N-oxides in modest to high yields with high chemoselectivity. This protocol allows a simple and clean synthesis of various 2-substituted pyridine N-oxides and the corresponding pyridine derivatives. Furthermore, straightforward one-pot iterative functionality of pyridine N-oxides could also be achieved simply by successive applications of two Grignard reagents.

Design and Fabrication of N-Alkyl-Polyethylenimine-Stabilized Iron Oxide Nanoclusters for Gene Delivery

PubMed Central

Liu, Gang; Wang, Zhiyong; Lee, Seulki; Ai, Hua; Chen, Xiaoyuan

2013-01-01

With the rapid development of nanotechnology, inorganic magnetic nanoparticles, especially iron oxide nanoparticles (IOs), have emerged as great vehicles for biomedical diagnostic and therapeutic applications. In order to rationally design IO-based gene delivery nanovectors, surface modification is essential and determines the loading and release of the gene of interest. Here we highlight the basic concepts and applications of nonviral gene delivery vehicles based on low molecular weight N-alkyl polyethylenimine-stabilized IOs. The experimental protocols related to these topics are described in this chapter. PMID:22568910

Saturated amine oxides: Part 8. Hydroacridines: Part 27. Effects of N-oxidation and of N-quaternization on the 15N NMR chemical shifts of N-methylpiperidine-derived mono-, bi-, and tricycloaliphatic tertiary amines.

PubMed

Potmischil, Francisc; Duddeck, Helmut; Nicolescu, Alina; Deleanu, Calin

2007-03-01

The (15)N chemical shifts of 13 N-methylpiperidine-derived mono-, bi- and tricycloaliphatic tertiary amines, their methiodides and their N-epimeric pairs of N-oxides were measured, and the contributions of specific structural parameters to the chemical shifts were determined by multilinear regression analysis. Within the examined compounds, the effects of N-oxidation upon the (15)N chemical shifts of the amines vary from +56 ppm to +90 ppm (deshielding), of which approx. +67.7 ppm is due to the inductive effect of the incoming N(+)--O(-) oxygen atom, whereas the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The effects of quaternization vary from -3.1 ppm to +29.3 ppm, of which approx. +8.9 ppm is due to the inductive effect of the incoming N(+)--CH(3) methyl group, and the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The shift effects of the C-alkyl substituents in the amines, the N-oxides and the methiodides are discussed. Copyright (c) 2007 John Wiley & Sons, Ltd.

40 CFR 721.10078 - Butanamide, 2-[(2-methoxy-4-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted...-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted...]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted]phenyl...

Copper(II)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine.

PubMed

Zhou, Ji-Ning; Fang, Qiang; Hu, Yi-Hu; Yang, Li-Yao; Wu, Fei-Fei; Xie, Lin-Jie; Wu, Jing; Li, Shijun

2014-02-14

A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse β-, γ- or ε-halo-substituted alkyl aryl ketones and α-, β- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.

Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to SN1 and SN2 Processes.

PubMed

Fu, Gregory C

2017-07-26

Classical methods for achieving nucleophilic substitutions of alkyl electrophiles (S N 1 and S N 2) have limited scope and are not generally amenable to enantioselective variants that employ readily available racemic electrophiles. Radical-based pathways catalyzed by chiral transition-metal complexes provide an attractive approach to addressing these limitations.

Is the liquid or the solid phase responsible for the low melting points of ionic liquids? Alkyl-chain-length dependence of thermodynamic properties of [C nmim][Tf 2N

NASA Astrophysics Data System (ADS)

Shimizu, Yoshitaka; Ohte, Yoko; Yamamura, Yasuhisa; Saito, Kazuya

2009-03-01

To establish the alkyl-chain-length dependences of thermodynamic properties of typical ionic liquids [C nmim][Tf 2N], the heat capacities of compounds with n = 2 and 18 were measured by adiabatic calorimetry. The comparison with other ionic liquids and typical molecular substances reveals that the low melting point of [C nmim][Tf 2N] with a short alkyl chain mainly originate in the large fusion entropy arising from the low entropy of the crystalline phase.

Synthesis and characterization of chitosan alkyl urea.

PubMed

Wang, Jing; Jiang, Ji-Zhou; Chen, Wei; Bai, Zheng-Wu

2016-07-10

Chitosan is a versatile material employed for various purposes in many fields including the development of chiral stationary phases for enantioseparation. Chitosan alkyl urea is a kind of intermediate used to prepare enantioseparation materials. In order to synthesize the intermediates, in the present work, a new way to prepare chitosan alkyl urea has been established: chitosan was first reacted with methyl chloroformate yielding N-methoxyformylated chitosan, which was then converted to chitosan alkyl urea through amine-ester exchange reaction. With a large excess of methyl chloroformate and primary amine of low stereohindrance, the amino group in chitosan could be almost completely converted to ureido group. The as-prepared chitosan alkyl urea derivatives were characterized by IR, (1)H NMR, (13)C NMR,(1)H-(1)H COSY and (1)H-(13)C HSQC NMR spectra. The chemical shifts of hydrogen and carbon atoms of glucose unit were assigned. It was found that the degree of substitution was obviously lower if cyclopropyl amine, aniline, tert-butyl amine and diethyl amine were used as reactants for the amine-ester exchange reaction. The reason was explained with the aid of theoretical calculations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptor.

PubMed

Jozwiak, Krzysztof; Targowska-Duda, Katarzyna M; Kaczor, Agnieszka A; Kozak, Joanna; Ligeza, Agnieszka; Szacon, Elzbieta; Wrobel, Tomasz M; Budzynska, Barbara; Biala, Grazyna; Fornal, Emilia; Poso, Antti; Wainer, Irving W; Matosiuk, Dariusz

2014-12-15

9 N-alkylated derivatives of dextromethorphan are synthesized and studied as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptors (nAChRs). In vitro activity towards α3β4 nicotinic acetylcholine receptor is determined using a patch-clamp technique and is in the micromolar range. Homology modeling, molecular docking and molecular dynamics of ligand-receptor complexes in POPC membrane are used to find the mode of interactions of N-alkylated dextromethorphan derivatives with α3β4 nAChR. The compounds, similarly as dextromethorphan, interact with the middle portion of α3β4 nAChR ion channel. Finally, behavioral tests confirmed potential application of the studied compounds for the treatment of addiction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Trifluoromethyl-substituted polymers

NASA Technical Reports Server (NTRS)

1993-01-01

Current work sponsored by the grant at Southwest Texas State University is directed toward the synthesis and characterization of: (1) N-alkylated polyamides derived from o-fluorinated diacids; (2) highly fluorinated polyethers; (3) polyesters derived from 2-hydroxy-2-propyl substituted arenes and/or 2,5-difluoroterephthalic acid; and (4) silicon-containing fluoropolymers. Work during the period from 1 July to 31 Dec. 1993 focused primarily on items 3 and 4 and on the development of a phosphorus containing modification of '12F-PEK.'

Investigation of J-shaped dose-responses induced by exposure to the alkylating agent N-methyl-N-nitrosourea.

PubMed

Chapman, Katherine E; Hoffmann, George R; Doak, Shareen H; Jenkins, Gareth J S

2017-07-01

Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade. However, no statistically significant decreases below control genotoxicity levels have been detected until recently. A hormetic-style dose-response following a 24h exposure to the alkylating agent N-methyl-N-nitrosourea (MNU) was observed in a previous study for HPRT mutagenesis in the human lymphoblastoid cell line AHH-1. A second recent study demonstrated a J-shaped dose-response for the induction of micronuclei by MNU in a 24h treatment in a similar test system. Following mechanistic investigations, it was hypothesized that p53 may be responsible for the observed hormetic phenomenon. As genotoxic carcinogens are a major causative factor of many cancers, consideration of hormesis in carcinogenesis could be important in safety assessment. The data examined here offer possible insights into hormesis, including its estimated prevalence, underlying mechanisms and lack of generalizability. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural Analysis and Application of n-Alkyl Cyanoacrylate Surgical Adhesives to the Fixation of Meshes for Hernia Repair.

PubMed

Fernández-Gutiérrez, Mar; Rodriguez-Mancheño, Marta; Pérez-Köhler, Bárbara; Pascual, Gemma; Bellón, Juan Manuel; Román, Julio San

2016-12-01

The article deals with a comparative analysis of the parameters of the polymerization in physiological conditions of three commercially available alkyl cyanoacrylates, n-butyl cyanoacrylate (GLUBRAN 2), n-hexyl cyanoacrylate (IFABOND), and n-octyl cyanoacrylate (EVOBOND), the cell behavior of the corresponding polymers and the application of these adhesives in the fixation of surgical polypropylene meshes for hernia repair in an animal model of rabbits. The results obtained demonstrate that the curing process depends on the nature of the alkyl residue of the ester group of cyanoacrylate molecules, being the heat of polymerization lower for the octyl derivative in comparison with the hexyl and butyl, and reaching a maximum temperature of 35 °C after a time of mixing with physiological fluids of 60-70 s. The cell behavior demonstrates that the three systems do not present toxicity for fibroblasts and low adhesion of cells, which is a positive result for application as tissue adhesives, especially for the fixation of abdominal polypropylene meshes for hernia repair. The animal experimentation indicates the excellent tolerance of the meshes fixed with the cyanoacrylic adhesives, during at least a period of 90 d, and guarantees a good adhesion for the application of hernia repair meshes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel quinazoline ring synthesis by cycloaddition of N-arylketenimines with N,N-disubstituted cyanamides.

PubMed

Shimizu, Masao; Oishi, Akihiro; Taguchi, Yoichi; Gama, Yasuo; Shibuya, Isao

2002-03-01

The reaction of N-aryl-substituted ketenimines with N,N-disubstituted cyanamides or (MeS)2C=N-CN under high pressure afforded 4-(N,N-disubstituted amino) or 4-(MeS)2C=N-substituted quinazoline derivatives, respectively. These products were formed by [4+2] cycloaddition between the aza-diene moieties of the N-arylsubstituted ketenimines and cyano groups. A 4-(unsubstituted amino)quinazoline derivative was synthesized by hydrolysis of the latter product.

Design and fabrication of N-alkyl-polyethylenimine-stabilized iron oxide nanoclusters for gene delivery.

PubMed

Liu, Gang; Wang, Zhiyong; Lee, Seulki; Ai, Hua; Chen, Xiaoyuan

2012-01-01

With the rapid development of nanotechnology, inorganic magnetic nanoparticles, especially iron oxide nanoparticles (IOs), have emerged as great vehicles for biomedical diagnostic and therapeutic applications. In order to rationally design IO-based gene delivery nanovectors, surface modification is essential and determines the loading and release of the gene of interest. Here we highlight the basic concepts and applications of nonviral gene delivery vehicles based on low molecular weight N-alkyl polyethylenimine-stabilized IOs. The experimental protocols related to these topics are described in this chapter. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

PubMed Central

Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

2015-01-01

ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus

Toxicity and biodegradability of selected N-substituted phenols under anaerobic conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donlon, B.; Razo-Flores, E.; Hwu, C.S.

1995-12-31

The anaerobic toxicity and biodegradability of N-substituted aromatics were evaluated in order to obtain information on their ultimate biotreatment. The toxicity of selected N-substituted aromatic compounds toward acetoclastic methanogens in granular sludge was measured in batch assays. This toxicity was highly correlated with compound hydrophobicity, indicating that partitioning into the bacterial membranes was an important factor in the toxicity. However, other factors, such as chemical interactions with key cell components, were suggested to be playing an important role. Nitroaromatic compounds were, on the average, over 300-fold more toxic than their amino-substituted counterparts. This finding suggests that the facile reduction ofmore » nitro-groups known to occur in anaerobic environments would result in a high level of detoxification. To test this hypothesis, continuous lab-scale upward-flow anaerobic sludge bed reactors treating 2-nitrophenol and 4-nitrophenol were established. The 4-nitrophenol was readily converted to the corresponding 4-aminophenol, whereas complete mineralization of 2-nitrophenol via intermediate formation of 2-aminophenol was obtained. These conversions led to a dramatic detoxification of the nitrophenols, because it was feasible to treat the highly toxic nitrophenolics at high organic loading rates.« less

Improving p-type doping efficiency in Al{sub 0.83}Ga{sub 0.17}N alloy substituted by nanoscale (AlN){sub 5}/(GaN){sub 1} superlattice with Mg{sub Ga}-O{sub N} δ-codoping: Role of O-atom in GaN monolayer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong, Hong-xia; Shi, Jun-jie, E-mail: jjshi@pku.edu.cn; Jiang, Xin-he

2015-01-15

We calculate Mg-acceptor activation energy E{sub A} and investigate the influence of O-atom, occupied the Mg nearest-neighbor, on E{sub A} in nanoscale (AlN){sub 5}/(GaN){sub 1} superlattice (SL), a substitution for Al{sub 0.83}Ga{sub 0.17}N disorder alloy, using first-principles calculations. We find that the N-atom bonded with Ga-atom is more easily substituted by O-atom and nMg{sub Ga}-O{sub N} (n = 1-3) complexes are favorable and stable in the SL. The O-atom plays a dominant role in reducing E{sub A}. The shorter the Mg-O bond is, the smaller the E{sub A} is. The Mg-acceptor activation energy can be reduced significantly by nMg{sub Ga}-O{submore » N} δ-codoping. Our calculated E{sub A} for 2Mg{sub Ga}-O{sub N} is 0.21 eV, and can be further reduced to 0.13 eV for 3Mg{sub Ga}-O{sub N}, which results in a high hole concentration in the order of 10{sup 20} cm{sup −3} at room temperature in (AlN){sub 5}/(GaN){sub 1} SL. Our results prove that nMg{sub Ga}-O{sub N} (n = 2,3) δ-codoping in AlN/GaN SL with ultrathin GaN-layer is an effective way to improve p-type doping efficiency in Al-rich AlGaN.« less

Double hetero-Michael addition of N-substituted hydroxylamines to quinone monoketals: synthesis of bridged isoxazolidines.

PubMed

Yin, Zhiwei; Zhang, Jinzhu; Wu, Jing; Liu, Che; Sioson, Kate; Devany, Matthew; Hu, Chunhua; Zheng, Shengping

2013-07-19

A general synthesis of bridged isoxazolidines from a double hetero-Michael addition of N-substituted hydroxylamines to quinone monoketals has been developed. The different addition order of N-benzylhydroxylamine and N-Boc hydroxylamine is also discussed. Moreover, the various functionalities in the isoxazolidine products allow facile derivatization.

N-substituted methyl maleamates as larvicidal compounds against Aedes aegypti (Diptera: Culicidae).

PubMed

Harburguer, Laura; Gonzalez, Paula V; Gonzalez Audino, Paola; Zerba, Eduardo; Masuh, Héctor

2018-02-01

Severe human arboviral diseases can be transmitted by the mosquito Aedes aegypti (L.), including dengue, chikungunya, zika, and yellow fever. The use of larvicides in containers that can result as potential breeding places and cannot be eliminated is the main alternative in control programs. However, their continuous and widespread use caused an increase in insecticide-resistant populations of this mosquito. The aim of this study was to evaluate the effect of three N-substituted methyl maleamates as larvicides on Ae. aegypti, the N-propyl methyl maleamate (PMM), N-butyl methyl maleamate (BMM), and N-hexyl methyl maleamate (HMM). These compounds could have a different mode of action from those larvicides known so far. We evaluated the larva mortality after 1 and 24 h of exposure and we found that mortality was fast and occurs within the first 60 min. HMM was slightly more effective with LC 50 values of 0.7 and 0.3 ppm for 1 and 24 h of exposure and LC 95 of 11 and 3 ppm. Our results demonstrate that N-substituted methyl maleamates have insecticidal properties for the control of Ae. aegypti larvae. These compounds could become useful alternatives to traditional larvicides after studying their insecticidal mechanism as well as their toxicity towards non target organisms.

Extended 3{beta}-alkyl steranes and 3-alkyl triaromatic steroids in crude oils and rock extracts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dahl, J.; Moldowan, J.M.; Summons, R.E.

1995-09-01

In oils and Precambian- to Miocene-age source rocks from varying depositional environments, we have conclusively identified several novel 3-alkyl sterane and triaromatic steroid series, including (1) 3{beta}-n-pentyl steranes, (2) 3{beta}-isopentyl steranes, (3) 3{beta}-n-hexyl steranes, (4) 3{beta}-n-hepatyl steranes, (5) 3,4-dimethyl steranes, (6) 3{beta}-butyl,4-methyl steranes, (7) triaromatic 3-n-pentyl steroids, and (8) triaromatic 3-isopentyl steroids. We have also tentatively identified additional homologs with 3-alkyl substituents as large as C{sub 11}. The relative abundances of these compounds vary substantially between samples, as indicated by (1) the ratio of 3{beta}-n-pentyl steranes to 3{beta}-isopentyl steranes and (2) the ratio of 3-n-pentyl triaromatic steroids to 3-isopentyl triaromaticmore » steroids. These data suggest possible utility for these parameters as tools for oil-source rock correlations and reconstruction of depositional environments. Although no 3-alkyl steroid natural products are currently known, several lines of evidence suggest that 3{beta}-alkyl steroids result from bacterial side-chain additions to diagenetic {delta}{sup 2}-sterenes.« less

Tuning the hydrophobicity overcomes unfavorable deprotonation making octylamino-substituted 7-nitrobenz-2-oxa-1,3-diazole (n-octylamino-NBD) a protonophore and uncoupler of oxidative phosphorylation in mitochondria.

PubMed

Denisov, Stepan S; Kotova, Elena A; Khailova, Ljudmila S; Korshunova, Galina A; Antonenko, Yuri N

2014-08-01

The environmentally sensitive fluorescent probe 7-nitrobenz-2-oxa-1,3-diazole (NBD) is generally utilized to monitor dynamic properties of membrane lipids and proteins. Here we studied the behavior of a homologous series of 4-n-alkylamino-substituted NBD derivatives (NBD-Cn; n=4, 6, 8, 9, 10, 12) in planar lipid bilayers, liposomes and isolated mitochondria. NBD-C10 induced proton conductivity in planar lipid membranes, while NBD-C4 was ineffective. The NBD-Cn compounds readily provoked proton permeability of neutral liposomes being less effective in negatively charged liposomes. NBD-Cn increased the respiration rate and reduced the membrane potential of isolated rat liver mitochondria. Remarkably, the bell-shaped dependence of the uncoupling activity of NBD-Cn on the alkyl chain length was found in mitochondria in contrast to the monotonous dependence in liposomes. The effect of NBD-Cn on the respiration correlated with that on proton permeability of the inner mitochondrial membrane, as measured by mitochondria swelling. Binding of NBD-Cn to mitochondria increased with n, as shown by fluorescence correlation spectroscopy. It was concluded that despite a pKa value of the amino group in NBD-Cn being about 10, i.e. far from the physiological pH range, the expected hindering of the uncoupling activity could be overcome by inserting the alkyl chain of a certain length. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhanced O-2 Selectivity versus N-2 by Partial Metal Substitution in Cu-BTC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sava Gallis, Dorina F.; Parkes, Marie V.; Greathouse, Jeffery A.

2015-03-24

Here, we describe the homogeneous substitution of Mn, Fe, and Co at various levels into a prototypical metal organic framework (MOP), namely Cu-BTC (HKUST-1), and the effect of that substitution on preferential gas sorption. Using a combination of density functional theory (DFT) calculations, postsynthetic metal substitutions, materials characterization, and gas sorption testing, we demonstrate that the identity of the metal ion has a quantifiable effect on their oxygen and nitrogen sorption properties at cryogenic temperatures. An excellent correlation is found between O-2/N-2 selectivities determined experimentally at 77 K and the difference in O-2 and N-2 binding energies calculated from DFTmore » modeling data: Mn > Fe Co >> Cu. Room temperature gas sorption studies were also performed and correlated with metal substitution. The Fe-exchanged sample shows a significantly higher nitrogen isosteric heat of adsorption at temperatures close to ambient conditions (273-298 K) as compared to all other metals studied, indicative of favorable interactions between N-2 and coordinatively unsaturated Fe metal centers. Interestingly, differences in gas adsorption results at cryogenic and room temperatures are evident; they are explained by comparing experimental results with DFT binding energies (0 K) and room temperature Grand Canonical Monte Carlo simulations.« less

Enhanced O 2 selectivity versus N 2 by partial metal substitution in Cu-BTC

DOE PAGES

Sava Gallis, Dorina F.; Parkes, Marie V.; Greathouse, Jeffery A.; ...

2015-03-05

Here we describe the homogeneous substitution of Mn, Fe and Co at various levels into a prototypical metal-organic framework (MOF), namely Cu-BTC (HKUST-1), and the effect of that substitution on preferential gas sorption. Using a combination of density functional theory (DFT) calculations, postsynthetic metal substitutions, materials characterization, and gas sorption testing, we demonstrate that the identity of the metal ion has a quantifiable effect on their oxygen and nitrogen sorption properties at cryogenic temperatures. An excellent correlation is found between O 2/N 2 selectivities determined experimentally at 77 K and the difference in O 2 and N 2 binding energiesmore » calculated from DFT modeling data: Mn > Fe > Co > Cu. Room temperature gas sorption studies were also performed and correlated with metal substitution. The Fe-exchanged sample shows a significantly higher nitrogen isosteric heat of adsorption at temperatures close to ambient conditions (273 K - 298 K) as compared to all other metals studied, indicative of favorable interactions between N 2 and coordinatively unsaturated Fe metal centers. Furthermore, differences in gas adsorption results at cryogenic and room temperatures are evident; they are explained by comparing experimental results with DFT binding energies (0 K) and room temperature Grand Canonical Monte Carlo simulations.« less

Synthesis of some N-substituted indole derivatives and their biological activities.

PubMed

el-Diwani, H; Nakkady, S S; Hishmat, O H; el-Shabrawy, O A; Mahmoud, S S

1992-03-01

Acylation of 2,3-diphenyl-5-methoxy-indole using ethyl chloroformate or chloroacetyl chloride in dimethylformamide and sodium hydride yielded the N-substituted derivatives 1 and 2, respectively. While Friedel-Crafts acylation using chloroacetyl chloride afforded di-4,6-chloroacetyl derivative 3, the reaction of the N-chloroacetyl derivative 2 with amines, hydrazines, urea, semicarbazide hydrochloride, thiophenol, benzimidazole-2-thiol, thiosemicarbazide, 2-mercaptoethanol and thioglycolic acid was studied. Several of the compounds were tested for their effect on arterial blood pressure, antiinflammatory and ulcerogenic activities.

Synthesis, characterization, and relative stabilities of self-assembled monolayers on gold generated from bidentate n-alkyl xanthic acids.

PubMed

Moore, H Justin; Colorado, Ramon; Lee, Han Ju; Jamison, Andrew C; Lee, T Randall

2013-08-27

A series of self-assembled monolayers (SAMs) on gold were generated by the adsorption of n-alkyl xanthic acids (NAXAs) having the general formula CH3(CH2)nOCS2H (n = 12-15). The structural features of these SAMs were characterized by optical ellipsometry, contact angle goniometry, polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS), and X-ray photoelectron spectroscopy (XPS). This series of xanthate SAMs were compared to SAMs generated from the corresponding n-alkanethiols and aliphatic dithiocarboxylic acids (ADTCAs). The collected data indicate that the NAXAs generate densely packed and well-ordered monolayers. The contact angles of hexadecane on the xanthate monolayers exhibited a large "odd-even" effect similar to that produced by the ADTCA SAMs. The relative stability of these bidentate xanthate SAMs was evaluated by monitoring the changes in ellipsometric thicknesses and wettability as a function of time under various conditions. The results demonstrate that SAMs formed from NAXAs are much less stable than analogous n-alkanethiolate and ADTCA SAMs.

Nanomechanical and nanotribological properties of Nb substituted TiN thin films

NASA Astrophysics Data System (ADS)

Krishna, M. Ghanashyam; Vasu, K.; Padmanabhan, K. A.

2012-06-01

Nanomechanical and nanotribological properties of Ti1-xNbxN (0≤x≤1) thin films were investigated as a function x. The films were deposited onto polycrystalline nuclear grade 316LN stainless steel (SS) substrate by radio frequency magnetron sputtering in 100% N2 plasma. The hardness and Young's modulus increased while the friction coefficient and wear volume decreased with increasing Nb substitution. The highest hardness achieved was 31GPa for x=0.77. At the same Nb concentration, the friction coefficient was 0.15 and the elastic recovery was 60%.

Discovery of 5-substituted tetrahydronaphthalen-2yl-methyl with N-phenyl-N-(piperidin-4-yl)propionamide derivatives as potent opioid receptor ligands.

PubMed

Deekonda, Srinivas; Wugalter, Lauren; Kulkarni, Vinod; Rankin, David; Largent-Milnes, Tally M; Davis, Peg; Bassirirad, Neemah M; Lai, Josephine; Vanderah, Todd W; Porreca, Frank; Hruby, Victor J

2015-09-15

A new series of novel opioid ligands have been designed and synthesized based on the 4-anilidopiperidine scaffold containing a 5-substituted tetrahydronaphthalen-2yl)methyl group with different N-phenyl-N-(piperidin-4-yl)propionamide derivatives to study the biological effects of these substituents on μ and δ opioid receptor interactions. Recently our group reported novel 4-anilidopiperidine analogues, in which several aromatic ring-contained amino acids were conjugated with N-phenyl-N-(piperidin-4-yl)propionamide and examined their biological activities at the μ and δ opioid receptors. In continuation of our efforts in these novel 4-anilidopiperidine analogues, we took a peptidomimetic approach in the present design, in which we substituted aromatic amino acids with tetrahydronaphthalen-2yl methyl moiety with amino, amide and hydroxyl substitutions at the 5th position. In in vitro assays these ligands, showed very good binding affinity and highly selective toward the μ opioid receptor. Among these, the lead ligand 20 showed excellent binding affinity (2 nM) and 5000 fold selectivity toward the μ opioid receptor, as well as functional selectivity in GPI assays (55.20 ± 4.30 nM) and weak or no agonist activities in MVD assays. Based on the in vitro bioassay results the lead compound 20 was chosen for in vivo assessment for efficacy in naïve rats after intrathecal administration. Compound 20 was not significantly effective in alleviating acute pain. This discrepancy between high in vitro binding affinity, moderate in vitro activity, and low in vivo activity may reflect differences in pharmacodynamics (i.e., engaging signaling pathways) or pharmacokinetics (i.e., metabolic stability). In sum, our data suggest that further optimization of this compound 20 is required to enhance in vivo activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neighbor-Directed Histidine N (s)–Alkylation: A Route to Imidazolium-Containing Phosphopeptide Macrocycles-Biopolymers | Center for Cancer Research

Cancer.gov

Our recently discovered, selective, on-resin route to N(s)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. Interestingly, these cationic moieties subsequently

Synergistic effects of N-ethyl-N-nitrosourea (an alkylating agent with a low Swain-Scott substrate constant) and X-rays in the stamen hairs of Tradescantia clone BNL 4430.

PubMed

Shima, N; Ichikawa, S

1997-01-01

The mutagenic interaction between N-ethyl-N-nitrosourea (ENU) and X-rays was tested in the stamen hairs of Tradescantia clone BNL 4430, a blue/pink heterozygote. ENU, a monofunctional alkylating agent with a low Swain-Scott substrate constant (s) of 0.26, exhibited a strong cytotoxicity. ENU-induced somatic pink mutation frequency per 10(4) hair-cell divisions increased with increasing ENU dose, with a slope of 1.243 on a log-log graph, the slope value being similar to that for X-ray-induced mutation frequency. Three out of five combined treatments with ENU and X-rays produced mutation frequencies significantly higher than those expected from the additive effects of the two mutagens. Clear synergistic effects were detected when relatively higher X-ray doses were applied, resembling those confirmed earlier between methyl methanesulfonate (MMS) and X-rays, although the s value for ENU is very much smaller than that (0.88) for MMS. It is therefore concluded that mutagenic interactions between alkylating agents and X-rays do not have any clear relationship with the s values.

Parallel and automated library synthesis of 2-long alkyl chain benzoazoles and azole[4,5-b]pyridines under microwave irradiation.

PubMed

Martínez-Palou, Rafael; Zepeda, L Gerardo; Höpfl, Herbert; Montoya, Ascensión; Guzmán-Lucero, Diego J; Guzmán, Javier

2005-01-01

A versatile route to 40-membered library of 2-long alkyl chain substituted benzoazoles (1 and 2) and azole[4,5-b]pyridines (3 and 4) via microwave-assisted combinatorial synthesis was developed. The reactions were carried out in both monomode and multimode microwave oven. With the latter, all reactions were performed in high-throughput experimental settings consisting of an 8 x 5 combinatorial library designed to synthesize 40 compounds. Each step, from the addition of reagents to the recovery of final products, was automated. The microwave-assisted N-long chain alkylation reactions of 2-alkyl-1H-benzimidazole (1) and 2-alkyl-1H-benzimidazole[4,5-b] pyridines (3) were also studied.

Photoswitchable Fluorescent Diarylethene Derivatives with Thiophene 1,1-Dioxide Groups: Effect of Alkyl Substituents at the Reactive Carbons

PubMed Central

Sumi, Takaki; Irie, Masahiro

2017-01-01

Photoswitching and fluorescent properties of sulfone derivatives of 1,2-bis(2-alkyl-4-methyl-5-phenyl-3-thienyl)perfluorocyclopentene, 1–5, having methyl, ethyl, n-propyl, i-propyl, and i-butyl substituents at the reactive carbons (2- and 2′-positions) of the thiophene 1,1-dioxide rings were studied. Diarylethenes 1–5 underwent isomerization reactions between open-ring and closed-ring forms upon alternate irradiation with ultraviolet (UV) and visible light and showed fluorescence in the closed-ring forms. The alkyl substitution at the reactive carbons affects the fluorescent property of the closed-ring isomers. The closed-ring isomers 2b–5b with ethyl, n-propyl, i-propyl, and i-butyl substituents show higher fluorescence quantum yields than 1b with methyl substituents. In polar solvents, the fluorescence quantum yield of 1b markedly decreases, while 2b–5b maintain the relatively high fluorescence quantum yields. Although the cycloreversion quantum yields of the derivatives with methyl, ethyl, n-propyl, and i-propyl substituents are quite low and in the order of 10−5, introduction of i-butyl substituents was found to increase the yield up to the order of 10−3. These results indicate that appropriate alkyl substitution at the reactive carbons is indispensable for properly controlling the photoswitching and fluorescent properties of the photoswitchable fluorescent diarylethenes, which are potentially applicable to super-resolution fluorescence microscopies. PMID:28869489

Triazolium based ionic liquid crystals: Effect of asymmetric substitution

DOE PAGES

Stappert, K.; Mudring, A. -V.

2015-01-27

A new series of ten different asymmetrical 1-dodecyl-3-alkyl-triazolium bromides, [C 12C nTr][Br], has been synthesized and their mesomorphic behavior studied by DSC (differential scanning calorimetry), POM (polarizing optical microscopy) and SAXS (small angle X-ray scattering). The influence of the chain length of the triazolium salts is investigated to explore the effect of asymmetric substitution on the phase behaviour of these compounds. For that reason, the length of one alkyl chain was varied from 14 to 1 carbon atoms (n = 14, 12, 10, 8–4, 2, 1) while the other alkyl chain was kept at 12 carbon. Single crystal X-ray structuremore » analysis of compounds [C 12C 12Tr][Br] and [C 12C 5Tr][Br] reveal that the cations adopt a U-shaped conformation with head-to-head arranged triazolium cores. In contrast, for [C 12C 1Tr][Br], a rod like shape of the cation with interdigitated alkyl chains is found. All investigated compounds are thermotropic liquid crystals. Higher ordered smectic phases, smectic C as well as smectic A phases were found depending on the chain length of the cation. Moreover, the clearing point temperature decreases with decreasing chain length with exception for the n-dodecyl-3-alkyltrizoliumbromides with the two shortest alkyl chains, [C 12C 2Tr][Br] and [C 12C 1Tr][Br], which present higher clearing temperatures (86 and 156 °C) and are structurally distinctly different.« less

Determination of the enthalpy of vaporization and prediction of surface tension for ionic liquid 1-alkyl-3-methylimidazolium propionate [C(n)mim][Pro](n = 4, 5, 6).

PubMed

Tong, Jing; Yang, Hong-Xu; Liu, Ru-Jing; Li, Chi; Xia, Li-Xin; Yang, Jia-Zhen

2014-11-13

With the use of isothermogravimetrical analysis, the enthalpies of vaporization, Δ(g)lH(o)m(T(av)), at the average temperature, T(av) = 445.65 K, for the ionic liquids (ILs) 1-alkyl-3-methylimidazolium propionate [C(n)mim][Pro](n = 4, 5, 6) were determined. Using Verevkin's method, the difference of heat capacities between the vapor phase and the liquid phase, Δ(g)lC(p)(o)m, for [C(n)mim][Pro](n = 2, 3, 4, 5, 6), were calculated based on the statistical thermodynamics. Therefore, with the use of Δ(g)lC(p)(o)m, the values of Δ(g)lH(o)m(T(av)) were transformed into Δ(g)lH(o)m(298), 126.8, 130.3, and 136.5 for [C(n)mim][Pro](n = 4, 5, 6), respectively. In terms of the new scale of polarity for ILs, the order of the polarity of [C(n)mim][Pro](n = 2, 3, 4, 5, 6) was predicted, that is, the polarity decreases with increasing methylene. A new model of the relationship between the surface tension and the enthalpy of vaporization for aprotic ILs was put forward and used to predict the surface tension for [C(n)mim][Pro](n = 2, 3, 4, 5, 6) and others. The predicted surface tension for the ILs is in good agreement with the experimental one.

Amphoteric Be in GaN: Experimental Evidence for Switching between Substitutional and Interstitial Lattice Sites

NASA Astrophysics Data System (ADS)

Tuomisto, Filip; Prozheeva, Vera; Makkonen, Ilja; Myers, Thomas H.; Bockowski, Michal; Teisseyre, Henryk

2017-11-01

We show that Be exhibits amphoteric behavior in GaN, involving switching between substitutional and interstitial positions in the lattice. This behavior is observed through the dominance of BeGa in the positron annihilation signals in Be-doped GaN, while the emergence of VGa at high temperatures is a consequence of the Be impurities being driven to interstitial positions. The similarity of this behavior to that found for Na and Li in ZnO suggests that this could be a universal property of light dopants substituting for heavy cations in compound semiconductors.

Amphoteric Be in GaN: Experimental Evidence for Switching between Substitutional and Interstitial Lattice Sites.

PubMed

Tuomisto, Filip; Prozheeva, Vera; Makkonen, Ilja; Myers, Thomas H; Bockowski, Michal; Teisseyre, Henryk

2017-11-10

We show that Be exhibits amphoteric behavior in GaN, involving switching between substitutional and interstitial positions in the lattice. This behavior is observed through the dominance of Be_{Ga} in the positron annihilation signals in Be-doped GaN, while the emergence of V_{Ga} at high temperatures is a consequence of the Be impurities being driven to interstitial positions. The similarity of this behavior to that found for Na and Li in ZnO suggests that this could be a universal property of light dopants substituting for heavy cations in compound semiconductors.

n-type conversion of SnS by isovalent ion substitution: Geometrical doping as a new doping route

PubMed Central

Ran, Fan-Yong; Xiao, Zewen; Toda, Yoshitake; Hiramatsu, Hidenori; Hosono, Hideo; Kamiya, Toshio

2015-01-01

Tin monosulfide (SnS) is a naturally p-type semiconductor with a layered crystal structure, but no reliable n-type SnS has been obtained by conventional aliovalent ion substitution. In this work, carrier polarity conversion to n-type was achieved by isovalent ion substitution for polycrystalline SnS thin films on glass substrates. Substituting Pb2+ for Sn2+ converted the majority carrier from hole to electron, and the free electron density ranged from 1012 to 1015 cm−3 with the largest electron mobility of 7.0 cm2/(Vs). The n-type conduction was confirmed further by the position of the Fermi level (EF) based on photoemission spectroscopy and electrical characteristics of pn heterojunctions. Density functional theory calculations reveal that the Pb substitution invokes a geometrical size effect that enlarges the interlayer distance and subsequently reduces the formation energies of Sn and Pb interstitials, which results in the electron doping. PMID:26020855

In search of a new class of stable nitroxide: synthesis and reactivity of a peri-substituted N,N-bissulfonylhydroxylamine.

PubMed

Patel, Bhaven; Carlisle, Julie; Bottle, Steven E; Hanson, Graeme R; Kariuki, Benson M; Male, Louise; McMurtrie, John C; Spencer, Neil; Grainger, Richard S

2011-04-07

Acyclic bissulfonylnitroxides have never been isolated, and degrade through fragmentation. In an approach to stabilising a bissulfonylnitroxide radical, the cyclic, peri-substituted N,N-bissulfonylhydroxylamine, 2-hydroxynaphtho[1,8-de][1,3,2]dithiazine 1,1,3,3-tetraoxide (1), has been prepared by formal nitrogen insertion into the sulfur-sulfur bond of a sulfinylsulfone, naphtho[1,8-cd][1,2]dithiole 1,1,2-trioxide. The heterocyclic ring of 1 is shown to adopt a sofa conformation by X-ray crystallography, with a pseudo-axial hydroxyl group. N,N-Bissulfonylhydroxylamine 1 displays high thermal, photochemical and hydrolytic stability compared to acyclic systems. EPR analysis reveals formation of the corresponding bissulfonylnitroxide 2 upon oxidation of 1 with the Ce(IV) salts CAN and CTAN. Although 2 does not undergo fragmentation, it cannot be isolated, since hydrogen atom abstraction to reform 1 occurs in situ. The stability and reactivity of 1 and 2 are compared with the known cyclic benzo-fused N,N-bissulfonylhydroxylamine, N-hydroxy-O-benzenedisulfonimide (6), for which the X-ray data, and EPR of the corresponding nitroxide 10, are also reported for the first time.

Calculation of Hammett Equation parameters for some N,N‧-bis (substituted-phenyl)-1,4-quinonediimines by density functional theory

NASA Astrophysics Data System (ADS)

Sein, Lawrence T.

2011-08-01

Hammett parameters σ' were determined from vertical ionization potentials, vertical electron affinities, adiabatic ionization potentials, adiabatic electron affinities, HOMO, and LUMO energies of a series of N, N' -bis (3',4'-substituted-phenyl)-1,4-quinonediimines computed at the B3LYP/6-311+G(2d,p) level on B3LYP/6-31G ∗ molecular geometries. These parameters were then least squares fit as a function of literature Hammett parameters. For N, N' -bis (4'-substituted-phenyl)-1,4-quinonediimines, the least squares fits demonstrated excellent linearity, with the square of Pearson's correlation coefficient ( r2) greater than 0.98 for all isomers. For N, N' -bis (3'-substituted-3'-aminophenyl)-1,4-quinonediimines, the least squares fits were less nearly linear, with r2 approximately 0.70 for all isomers when derived from calculated vertical ionization potentials, but those from calculated vertical electron affinities usually greater than 0.90.

Reactions of Tributylstannyl Anioniods with Alkyl Bromides.

DTIC Science & Technology

1981-09-28

g (12 mmol) of cesium tert-butoxide was added to the reaction vessel before the addition of n-butyllithium. Alkylation of Tributylstannyl Anionoids...Dry reaction vessels were purged with argon. The desired alkyl halide (1.0 mmol unless noted) and any desired additive were added to the reaction ...OFFICE OF NAVAL RESEARCH Contract N00014-79-C-0584 Task No. NR 053-714 TECHNICAL REPORT No. 2 Reactions of Tributylstannyl Anionoids with Alkyl

Theoretical Studies of the Glycosidation of 2-O-Substituted 5-Fluorouracil: N-Regioselective Synthesis with the Phase-Transfer-Catalysis Method.

PubMed

Wang, Yi-Gui; Barnes, Ericka C

2017-11-22

The observed N-regioselective glycosidation of 2-O-substituted 5-fluorouracil (5-FU) via the phase-transfer-catalysis (PTC) method was investigated computationally. The Gibbs free energy reaction barrier of the N-reaction between the 5-FU anion and 1-bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-α-d-glucopyranose was computed at the MP2/6-311++G(2d,p)//B3LYP/6-31+G* level. The calculated transition states were, in general, quite "loose", with the ambident reaction sites at the N3- or O4-positions on 5-FU located approximately 2.0 Å from the anomeric carbon. With the S N 2 mechanism, the formation of β-glycosides was explained by the characteristics of transition states, and the N-regioselectivity was explained by three considerations: (1) the conformations of initial complexes and the structural requirement of the reactions; (2) the formation of an ionic pair between nBu 4 N + and 2-O-substituted 5-FU anions; and (3) the thermodynamic conversion of O-glycosides to N-glycosides. The reactions between the oxocarbenium ion and the 2-O-substituted 5-FU anions (the fast step of S N 1 mechanism) were also examined at the same level of theory. Because there were no "promoters" to extract Br in the PTC method, the S N 1 mechanism might have an unfavorably high barrier to produce oxocarbenium ion. However, both the formation of β-glycosides and the experimentally observed N-regioselectivity could also be explained by the S N 1 mechanism: The former was explained by the neighboring group participation, and the latter was explained by the formation of ionic pairs between nBu 4 N + and 2-O-substituted 5-FU anions. The formation of ionic pairs possibly changed the diffusion-controlled mechanism into an activation-controlled mechanism. Two factors were demonstrated by Marcus theory to play an important role for the experimentally observed N-resioselectivity in the PTC method: (1) the thermodynamic stability of N-products over O-products; (2) the formation of ionic pair between nBu 4

Total synthesis of (+)-batzelladine A and (-)-batzelladine D via [4 + 2]-annulation of vinyl carbodiimides with N-alkyl imines.

PubMed

Arnold, Michael A; Day, Kenneth A; Durón, Sergio G; Gin, David Y

2006-10-11

A diastereoselective [4 + 2]-annulation of vinyl carbodiimides with chiral N-alkyl imines has been developed to access the stereochemically rich polycyclic guanidine cores of the batzelladine alkaloids. Application of this strategy, together with additional key steps such as long-range directed hydrogenation and diastereoselective intramolecular iodo-amination, led to highly convergent total syntheses of (-)-batzelladine D and (+)-batzelladine A with excellent stereocontrol.

Solid state isostructural behavior and quantified limiting substitution kinetics in Schiff-base bidentate ligand complexes fac-[Re(O,N-Bid)(CO)3(MeOH)](n).

PubMed

Brink, Alice; Visser, Hendrik G; Roodt, Andreas

2014-12-01

A range of N,O-donor atom salicylidene complexes of the type fac-[M(O,N-Bid)(CO)3(L)](n) (O,N-Bid = anionic N,O-bidentate ligands; L = neutral coordinated ligand) have been studied. The unique feature of the complexes which crystallize in a monoclinic isostructural space group for complexes containing methanol in the sixth position (L = MeOH) is highlighted. The reactivity and stability of the complexes were evaluated by rapid stopped-flow techniques, and the methanol substitution by a range of pyridine type ligands indicates significant activation by the N,O-salicylidene type of bidentate ligands as observed from the variation in the second-order rate constants. In particular, following the introduction of the sterically demanding and electron rich cyclohexyl salicylidene moiety on the bidentate ligand, novel limiting kinetic behavior is displayed by all entering ligands, thus enabling a systematic probe and manipulation of the limiting kinetic constants. Clear evidence of an interchange type of intimate mechanism for the methanol substitution is produced. The equilibrium and rate constants (25 °C) for the two steps in the dissociative interchange mechanism for methanol substitution in fac-[Re(Sal-Cy)(CO)3(MeOH)] (5) by the pyridine type ligands 3-chloropyridine, pyridine, 4-picoline, and DMAP are k3 (s(-1)), 40 ± 4, 13 ± 2, 10.4 ± 0.7, and 2.11 ± 0.09, and K2 (M(-1)), 0.13 ± 0.01, 0.21 ± 0.03, 0.26 ± 0.02, and 1.8 ± 0.1, respectively.

CRM1 inhibitory and antiproliferative activities of novel 4'-alkyl substituted klavuzon derivatives.

PubMed

Kanbur, Tuğçe; Kara, Murat; Kutluer, Meltem; Şen, Ayhan; Delman, Murat; Alkan, Aylin; Otaş, Hasan Ozan; Akçok, İsmail; Çağır, Ali

2017-08-15

Klavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one derivatives showing promising antiproliferative activities in variety of cancer cell lines. In this work, racemic syntheses of nine novel 4'-alkyl substituted klavuzon derivatives were completed in eight steps and anticancer properties of these compounds were evaluated. It is found that size of the substituent has dramatic effect over the potency and selectivity of the cytotoxic activity in cancerous and healthy pancreatic cell lines. The size of the substituent can also effect the CRM1 inhibitory properties of klavuzon derivatives. Strong cytotoxic activity and CRM1 inhibition can be observed only when a small substituent present at 4'-position of naphthalen-1-yl group. However, these substituents makes the molecule more cytotoxic in healthy pancreatic cells rather than cancerous pancreatic cells. Among the tested compounds 1,2,3,4-tetrahydrophenanthren-9-yl substituted lactone was the most cytotoxic compound and its antiproliferative activity was also tested in 3D spheroids generated from HuH-7 cell lines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and characterization of a novel long-alkyl-chain ester-substituted benzimidazole gelator and its octan-1-ol solvate.

PubMed

Geiger, H Cristina; Zick, Patricia L; Roberts, William R; Geiger, David K

2017-04-01

The synthesis of a novel benzimidazole derivative with a long-chain-ester substituent, namely methyl 8-[4-(1H-benzimidazol-2-yl)phenoxy]octanoate, (3), is reported. Ester (3) shows evidence of aggregation in solution and weak gelation ability with toluene. The octan-1-ol solvate, methyl 8-[4-(1H-benzimidazol-2-yl)phenoxy]octanoate octan-1-ol monosolvate, C 22 H 26 N 2 O 3 ·C 8 H 18 O, (4), exhibits a four-molecule hydrogen-bonded motif in the solid state, with N-H...O hydrogen bonds between benzimidazole molecules and O-H...N hydrogen bonds between the octan-1-ol solvent molecules and the benzimidazole unit. The alkyl chains of the ester and the octan-1-ol molecules are in unfolded conformations. The phenylene ring is canted by 10.27 (6)° from the plane of the benzimidazole ring system. H...C contacts make up 20.7% of the Hirshfeld surface coverage. Weak C-H...π interactions involving the benzimidazole alkyl chain and three aromatic rings are observed.

Screening for Neuraminidase Inhibitor Resistance Markers among Avian Influenza Viruses of the N4, N5, N6, and N8 Neuraminidase Subtypes.

PubMed

Choi, Won-Suk; Jeong, Ju Hwan; Kwon, Jin Jung; Ahn, Su Jeong; Lloren, Khristine Kaith S; Kwon, Hyeok-Il; Chae, Hee Bok; Hwang, Jungwon; Kim, Myung Hee; Kim, Chul-Joong; Webby, Richard J; Govorkova, Elena A; Choi, Young Ki; Baek, Yun Hee; Song, Min-Suk

2018-01-01

Several subtypes of avian influenza viruses (AIVs) are emerging as novel human pathogens, and the frequency of related infections has increased in recent years. Although neuraminidase (NA) inhibitors (NAIs) are the only class of antiviral drugs available for therapeutic intervention for AIV-infected patients, studies on NAI resistance among AIVs have been limited, and markers of resistance are poorly understood. Previously, we identified unique NAI resistance substitutions in AIVs of the N3, N7, and N9 NA subtypes. Here, we report profiles of NA substitutions that confer NAI resistance in AIVs of the N4, N5, N6, and N8 NA subtypes using gene-fragmented random mutagenesis. We generated libraries of mutant influenza viruses using reverse genetics (RG) and selected resistant variants in the presence of the NAIs oseltamivir carboxylate and zanamivir in MDCK cells. In addition, two substitutions, H274Y and R292K (N2 numbering), were introduced into each NA gene for comparison. We identified 37 amino acid substitutions within the NA gene, 16 of which (4 in N4, 4 in N5, 4 in N6, and 4 in N8) conferred resistance to NAIs (oseltamivir carboxylate, zanamivir, or peramivir) as determined using a fluorescence-based NA inhibition assay. Substitutions conferring NAI resistance were mainly categorized as either novel NA subtype specific (G/N147V/I, A246V, and I427L) or previously reported in other subtypes (E119A/D/V, Q136K, E276D, R292K, and R371K). Our results demonstrate that each NA subtype possesses unique NAI resistance markers, and knowledge of these substitutions in AIVs is important in facilitating antiviral susceptibility monitoring of NAI resistance in AIVs. IMPORTANCE The frequency of human infections with avian influenza viruses (AIVs) has increased in recent years. Despite the availability of vaccines, neuraminidase inhibitors (NAIs), as the only available class of drugs for AIVs in humans, have been constantly used for treatment, leading to the inevitable emergence

The Enzymatic Release of O6-methylguanine and 3-methyladenine from DNA Reacted with the Carcinogen N-methyl-N-nitrosourea

PubMed Central

Kirtikar, D. M.; Goldthwait, D. A.

1974-01-01

Endonuclease II (deoxyribonucleate oligonucleotidohydrolase, EC 3.1.4.30) of Escherichia coli has been shown to break phosphodiester bonds in alkylated DNA and depurinated DNA. The hypothesis that depurination is a step in the mechanism of the reaction with alkylated DNA is supported by in vitro experiments with DNA reacted with N-methyl-N-nitrosourea. Endonuclease II releases O6-methylguanine and 3-methyladenine, but not 7-methylguanine, from DNA that has been methylated by the carcinogen N-methyl-N-nitrosourea. PMID:4600266

A comparative study of two novel unsymmetrically substituted triazacyclohexanes

NASA Astrophysics Data System (ADS)

Lamraoui, Hanane; Messai, Amel; Bilge, Duygu; Bilge, Metin; Bouchemma, Ahcen; Parlak, Cemal

2017-06-01

Novel unsymmetrically N-substituted N,N‧-R1N″-R2-1,3,5-triazacyclohexanes (1b and 2b; R1 = p-chlorophenyl or p-methoxyphenyl and R2 = butyl or cyclohexyl) have been synthesized in a good yield from condensation reaction by excess amine. Both triazacyclohexane rings have chair conformation. However, 1b adopts diaxial orientation of aryl groups and an equatorial form of alkyl group whereas 2b prefers an axial orientation of the alkyl group and diequatorial forms of aryl groups. 1b is consolidated by weak C-H⋯π interactions. Intra-molecular C-H⋯O or C-H⋯N hydrogen bonds and C-H⋯π may be effective in the stabilization of 2b. Both compounds have showed moderate antimicrobial activity, but 1b exhibits higher activity than 2b. All experimental results are found in good support to theoretical data. Findings of research may be helpful guide for the medicinal chemists and the field is further open for pharmacokinetics studies.

Grafting C8-C16 alkyl groups altered the self-assembly and curcumin -loading properties of sodium caseinate in water.

PubMed

Zhang, Yaqiong; Yang, Puyu; Yao, Fangyi; Liu, Jie; Yu, Liangli Lucy

2018-02-01

The data presented here are related to the research article entitled "Synthesis and characterization of alkylated caseinate, and its structure-curcumin loading property relationship in water" (Zhang et al., 2018) [1]. This data article reports the detailed spectra information for 1 H NMR, 13 C NMR and UPLC-Q-TOF MS of the N-succinimidyl fatty acid esters with various alkyl chain lengths (Cn-NHSs, n = 8, 12, 14 and 16). 1 H NMR, 13 C NMR and UPLC-Q-TOF MS spectra for C16-NHS are shown as an example. Then the stacked 1 H NMR spectra of the obtained alkylated caseinates (Cn-caseinates, n = 8, 12, 14 and 16) are provided. The surface hydrophobicity index (S 0 ) of Cn-caseinates with different substitution degrees (SD) of alkyl groups is shown. Additionally, Visual appearances for the formed aqueous dispersions of curcumin-loaded native caseinate (NaCas) and Cn-caseinates self-assemblies are shown. X-ray diffraction patterns of curcumin, C16-caseinate, its physical mixture and curcumin-loaded C16-caseinate self-assemblies are examined. The re-dispersibility and short-term storage stability of the curcumin-loaded NaCas and C16-caseinate self-assemblies are also studied.

Asymmetric Alkyl Side-Chain Engineering of Naphthalene Diimide-Based n-Type Polymers for Efficient All-Polymer Solar Cells.

PubMed

Jia, Tao; Li, Zhenye; Ying, Lei; Jia, Jianchao; Fan, Baobing; Zhong, Wenkai; Pan, Feilong; He, Penghui; Chen, Junwu; Huang, Fei; Cao, Yong

2018-02-13

The design and synthesis of three n-type conjugated polymers based on a naphthalene diimide-thiophene skeleton are presented. The control polymer, PNDI-2HD, has two identical 2-hexyldecyl side chains, and the other polymers have different alkyl side chains; PNDI-EHDT has a 2-ethylhexyl and a 2-decyltetradecyl side chain, and PNDI-BOOD has a 2-butyloctyl and a 2-octyldodecyl side chain. These copolymers with different alkyl side chains exhibit higher melting and crystallization temperatures, and stronger aggregation in solution, than the control copolymer PNDI-2HD that has the same side chain. Polymer solar cells based on the electron-donating copolymer PTB7-Th and these novel copolymers exhibit nearly the same open-circuit voltage of 0.77 V. Devices based on the copolymer PNDI-BOOD with different side chains have a power-conversion efficiency of up to 6.89%, which is much higher than the 4.30% obtained with the symmetric PNDI-2HD. This improvement can be attributed to the improved charge-carrier mobility and the formation of favorable film morphology. These observations suggest that the molecular design strategy of incorporating different side chains can provide a new and promising approach to developing n-type conjugated polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Unique Determinants of Neuraminidase Inhibitor Resistance among N3, N7, and N9 Avian Influenza Viruses.

PubMed

Song, Min-Suk; Marathe, Bindumadhav M; Kumar, Gyanendra; Wong, Sook-San; Rubrum, Adam; Zanin, Mark; Choi, Young-Ki; Webster, Robert G; Govorkova, Elena A; Webby, Richard J

2015-11-01

Human infections with avian influenza viruses are a serious public health concern. The neuraminidase (NA) inhibitors (NAIs) are the frontline anti-influenza drugs and are the major option for treatment of newly emerging influenza. Therefore, it is essential to identify the molecular markers of NAI resistance among specific NA subtypes of avian influenza viruses to help guide clinical management. NAI-resistant substitutions in NA subtypes other than N1 and N2 have been poorly studied. Here, we identified NA amino acid substitutions associated with NAI resistance among influenza viruses of N3, N7, and N9 subtypes which have been associated with zoonotic transmission. We applied random mutagenesis and generated recombinant influenza viruses carrying single or double NA substitution(s) with seven internal genes from A/Puerto Rico/8/1934 (H1N1) virus. In a fluorescence-based NA inhibition assay, we identified three categories of NA substitutions associated with reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir): (i) novel subtype-specific substitutions in or near the enzyme catalytic site (R152W, A246T, and D293N, N2 numbering), (ii) subtype-independent substitutions (E119G/V and/or D and R292K), and (iii) substitutions previously reported in other subtypes (Q136K, I222M, and E276D). Our data show that although some markers of resistance are present across NA subtypes, other subtype-specific markers can only be determined empirically. The number of humans infected with avian influenza viruses is increasing, raising concerns of the emergence of avian influenza viruses resistant to neuraminidase (NA) inhibitors (NAIs). Since most studies have focused on NAI-resistance in human influenza viruses, we investigated the molecular changes in NA that could confer NAI resistance in avian viruses grown in immortalized monolayer cells, especially those of the N3, N7, and N9 subtypes, which have caused human infections. We identified not only numerous NAI

Effect of ionic strength and cationic DNA affinity binders on the DNA sequence selective alkylation of guanine N7-positions by nitrogen mustards

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartley, J.A.; Forrow, S.M.; Souhami, R.L.

Large variations in alkylation intensities exist among guanines in a DNA sequence following treatment with chemotherapeutic alkylating agents such as nitrogen mustards, and the substituent attached to the reactive group can impose a distinct sequence preference for reaction. In order to understand further the structural and electrostatic factors which determine the sequence selectivity of alkylation reactions, the effect of increase ionic strength, the intercalator ethidium bromide, AT-specific minor groove binders distamycin A and netropsin, and the polyamine spermine on guanine N7-alkylation by L-phenylalanine mustard (L-Pam), uracil mustard (UM), and quinacrine mustard (QM) was investigated with a modification of the guanine-specificmore » chemical cleavage technique for DNA sequencing. The result differed with both the nitrogen mustard and the cationic agent used. The effect, which resulted in both enhancement and suppression of alkylation sites, was most striking in the case of netropsin and distamycin A, which differed from each other. DNA footprinting indicated that selective binding to AT sequences in the minor groove of DNA can have long-range effects on the alkylation pattern of DNA in the major groove.« less

Substitutions in position 222 of haemagglutinin of pandemic influenza A (H1N1) 2009 viruses in Spain.

PubMed

Ledesma, Juan; Pozo, Francisco; Pérez Ruiz, Mercedes; Navarro, Jose María; Piñeiro, Luis; Montes, Milagros; Pérez Castro, Sonia; Suárez Fernández, Jonathan; García Costa, Juan; Fernández, Mirian; Galán, Juan Carlos; Cuevas, María Teresa; Casas, Inmaculada; Pérez Breña, Pilar

2011-05-01

A change of aspartic acid (D) to glycine (G) at position 222 in the haemagglutinin (HA) protein of pandemic influenza A (H1N1) 2009 viruses was described in Norway on November 2009 with considerable frequency in fatal and severe cases. This change was detected in other countries and was related only with severe disease. Other substitutions to glutamic acid (E) or asparagine (N) at position 222 were detected among pandemic viruses but it is unclear what implications might have in terms of severity. To analyse the appearance of amino acid substitutions at position 222 in the HA protein of circulating viruses in Spain and to determine their relationships with the disease symptoms observed. Pandemic influenza A (H1N1) 2009 viruses detected in respiratory samples of 273 severe and 533 non-severe cases from different Spanish regions were selected for sequencing of a partial segment of HA1 subunit and studied to monitor substitutions at position 222. D222G substitution was only detected in viruses from 14 severe cases (5.12%). D222E was found in viruses from 47 severe (17.21%) and from 52 non-severe cases (9.75%). D222N occurred in viruses from 3 additional severe cases (0.37%). Appearance of D222G and D222E substitution in HA of pandemic influenza A (H1N1) viruses circulating in Spain might be related with severe respiratory disease. Copyright © 2011 Elsevier B.V. All rights reserved.

N-methylpurine DNA glycosylase inhibits p53-mediated cell cycle arrest and coordinates with p53 to determine sensitivity to alkylating agents.

PubMed

Song, Shanshan; Xing, Guichun; Yuan, Lin; Wang, Jian; Wang, Shan; Yin, Yuxin; Tian, Chunyan; He, Fuchu; Zhang, Lingqiang

2012-08-01

Alkylating agents induce genome-wide base damage, which is repaired mainly by N-methylpurine DNA glycosylase (MPG). An elevated expression of MPG in certain types of tumor cells confers higher sensitivity to alkylation agents because MPG-induced apurinic/apyrimidic (AP) sites trigger more strand breaks. However, the determinant of drug sensitivity or insensitivity still remains unclear. Here, we report that the p53 status coordinates with MPG to play a pivotal role in such process. MPG expression is positive in breast, lung and colon cancers (38.7%, 43.4% and 25.3%, respectively) but negative in all adjacent normal tissues. MPG directly binds to the tumor suppressor p53 and represses p53 activity in unstressed cells. The overexpression of MPG reduced, whereas depletion of MPG increased, the expression levels of pro-arrest gene downstream of p53 including p21, 14-3-3σ and Gadd45 but not proapoptotic ones. The N-terminal region of MPG was specifically required for the interaction with the DNA binding domain of p53. Upon DNA alkylation stress, in p53 wild-type tumor cells, p53 dissociated from MPG and induced cell growth arrest. Then, AP sites were repaired efficiently, which led to insensitivity to alkylating agents. By contrast, in p53-mutated cells, the AP sites were repaired with low efficacy. To our knowledge, this is the first direct evidence to show that a DNA repair enzyme functions as a selective regulator of p53, and these findings provide new insights into the functional linkage between MPG and p53 in cancer therapy.

C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin: a new cleavage mixture prevents their formation.

PubMed

Stathopoulos, Panagiotis; Papas, Serafim; Tsikaris, Vassilios

2006-03-01

Decomposition of the resin linkers during TFA cleavage of the peptides in the Fmoc strategy leads to alkylation of sensitive amino acids. The C-terminal amide alkylation, reported for the first time, is shown to be a major problem in peptide amides synthesized on the Rink amide resin. This side reaction occurs as a result of the Rink amide linker decomposition under TFA treatment of the peptide resin. The use of 1,3-dimethoxybenzene in a cleavage cocktail prevents almost quantitatively formation of C-terminal N-alkylated peptide amides. Oxidized by-product in the tested Cys- and Met-containing peptides were not observed, even if thiols were not used in the cleavage mixture. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.

Analytical characterization of bioactive N-benzyl-substituted phenethylamines and 5-methoxytryptamines.

PubMed

Brandt, Simon D; Elliott, Simon P; Kavanagh, Pierce V; Dempster, Nicola M; Meyer, Markus R; Maurer, Hans H; Nichols, David E

2015-04-15

Substances based on the N-(2-methoxybenzyl)phenethylamine template ('NBOMe' derivatives) play an important role in medicinal research but some of these derivatives have also appeared as 'research chemicals' for recreational use which has attracted attention worldwide. A major challenge associated with newly emerging substances includes the lack of analytical data and the ability to correctly identify positional isomers. Six N-benzylphenethylamines based on the 2,5-dimethoxy-4-iodophenethylamine structure ('25I') and twelve substituted N-benzyl-5-methoxytryptamines ('5MT') have been prepared and extensively characterized. Techniques used for characterization were gas chromatography/ion trap mass spectrometry in electron and chemical ionization mode, liquid chromatography/diode array detection (DAD), infrared spectroscopy, electrospray high mass accuracy quadrupole time-of-flight tandem mass spectrometry, and triple quadrupole tandem mass spectrometry. The characterization of 18 'NBOMe' compounds provided a comprehensive collection of chromatographic and spectral data. Four groups of three positional isomers, i.e. 25I-NB2OMe, 25I-NB3OMe, 25I-NB4OMe, 25I-NB2B, 25I-NB3B, 25I-NB4B and their 5-methoxytryptamine counterparts, were included and assessed for ability to obtain differentiation. Six meta-substituted N-benzyl derivatives of 5-methoxytryptamine (CF3, F, CH3, Cl, I, SCH3) were also studied. The implementation of mass spectral techniques was helpful for the differentiation between isomers, for example, when considering the difference in a number of ion ratios. This was considered beneficial in cases where chromatographic separation was only partially achieved under liquid chromatography (LC) conditions. The use of LC/DAD analysis was also found to be valuable for this particular purpose, which confirmed the integrative value of complementary techniques used in areas related to forensic toxicology. Copyright © 2015 John Wiley & Sons, Ltd.

Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives.

PubMed

Kraemer, Thomas; Maurer, Hans H

2002-04-01

This paper reviews the toxicokinetics of amphetamines. The designer drugs MDA (methylenedioxy-amphetamine, R,S-1-(3;,4;-methylenedioxyphenyl)2-propanamine), MDMA (R,S-methylenedioxymethamphetamine), and MDE (R,S-methylenedioxyethylamphetamine), as well as BDB (benzodioxolylbutanamine; R,S-1-(1;,3;-benzodioxol-5;-yl)-2-butanamine or R,S-1-(3;,4;-methylenedioxyphenyl)-2-butanamine) and MBDB (R,S-N-methyl-benzodioxolylbutanamine), were taken into consideration, as were the following N-alkylated amphetamine derivatives: amphetaminil, benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, methamphetamine, prenylamine, and selegiline. English-language publications from 1995 to 2000 were reviewed. Papers describing identification of metabolites or cytochrome P450 isoenzyme-dependent metabolism and papers containing pharmacokinetic/toxicokinetic data were considered and summarized. The implications of toxicokinetics for toxicologic assessment or for interpretation in forensic cases are discussed.

Thermodynamic, Spectroscopic, and Computational Studies of f -Element Complexation by N -Hydroxyethyl-diethylenetriamine- N,N ', N ", N"-tetraacetic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grimes, Travis S.; Heathman, Colt R.; Jansone-Popova, Santa

Potentiometric and spectroscopic techniques were combined with DFT calculations to probe the coordination environment and determine thermodynamic features of trivalent f-element complexation by N-hydroxyethyl-diethylenetriamine-N,N',N",N"-tetraacetic acid, HEDTTA. Ligand protonation constants and lanthanide stability constants were determined using potentiometry. Five protonation constants were accessible in I = 2.0 M (H +/Na +)ClO 4. UV–vis spectroscopy was used to determine stability constants for Nd 3+ and Am 3+ complexation with HEDTTA. Luminescence spectroscopy indicates two water molecules in the inner coordination sphere of the Eu/HEDTTA complex, suggesting HEDTTA is heptadentate. Luminescence data was supported by DFT calculations, which demonstrate that substitution of themore » acetate pendant arm by a N-hydroxyethyl group weakens the metal–nitrogen bond. This bond elongation is reflected in HEDTTA’s ability to differentiate trivalent actinides from trivalent lanthanides. The trans-lanthanide Ln/HEDTTA complex stability trend is analogous to Ln/DTPA complexation; however, the loss of one chelate ring resulting from structural substitution weakens the complexation by ~3 orders of magnitude. Successful separation of trivalent americium from trivalent lanthanides was demonstrated when HEDTTA was utilized as aqueous holdback complexant in a liquid–liquid system. Time-dependent extraction studies for HEDTTA were compared to diethylenetriamine-N,N,N',N",N"-pentaacetic acid (DTPA) and N-hydroxyethyl-ethylenediamine-N,N',N'-triacetic acid (HEDTA). The results presented here indicate substantially enhanced phase-transfer kinetic rates for mixtures containing HEDTTA.« less

Thermodynamic, Spectroscopic, and Computational Studies of f -Element Complexation by N -Hydroxyethyl-diethylenetriamine- N,N ', N ", N"-tetraacetic Acid

DOE PAGES

Grimes, Travis S.; Heathman, Colt R.; Jansone-Popova, Santa; ...

2017-01-24

Potentiometric and spectroscopic techniques were combined with DFT calculations to probe the coordination environment and determine thermodynamic features of trivalent f-element complexation by N-hydroxyethyl-diethylenetriamine-N,N',N",N"-tetraacetic acid, HEDTTA. Ligand protonation constants and lanthanide stability constants were determined using potentiometry. Five protonation constants were accessible in I = 2.0 M (H +/Na +)ClO 4. UV–vis spectroscopy was used to determine stability constants for Nd 3+ and Am 3+ complexation with HEDTTA. Luminescence spectroscopy indicates two water molecules in the inner coordination sphere of the Eu/HEDTTA complex, suggesting HEDTTA is heptadentate. Luminescence data was supported by DFT calculations, which demonstrate that substitution of themore » acetate pendant arm by a N-hydroxyethyl group weakens the metal–nitrogen bond. This bond elongation is reflected in HEDTTA’s ability to differentiate trivalent actinides from trivalent lanthanides. The trans-lanthanide Ln/HEDTTA complex stability trend is analogous to Ln/DTPA complexation; however, the loss of one chelate ring resulting from structural substitution weakens the complexation by ~3 orders of magnitude. Successful separation of trivalent americium from trivalent lanthanides was demonstrated when HEDTTA was utilized as aqueous holdback complexant in a liquid–liquid system. Time-dependent extraction studies for HEDTTA were compared to diethylenetriamine-N,N,N',N",N"-pentaacetic acid (DTPA) and N-hydroxyethyl-ethylenediamine-N,N',N'-triacetic acid (HEDTA). The results presented here indicate substantially enhanced phase-transfer kinetic rates for mixtures containing HEDTTA.« less

Critical role of alkyl chain branching of organic semiconductors in enabling solution-processed N-channel organic thin-film transistors with mobility of up to 3.50 cm² V(-1) s(-1).

PubMed

Zhang, Fengjiao; Hu, Yunbin; Schuettfort, Torben; Di, Chong-an; Gao, Xike; McNeill, Christopher R; Thomsen, Lars; Mannsfeld, Stefan C B; Yuan, Wei; Sirringhaus, Henning; Zhu, Daoben

2013-02-13

Substituted side chains are fundamental units in solution processable organic semiconductors in order to achieve a balance of close intermolecular stacking, high crystallinity, and good compatibility with different wet techniques. Based on four air-stable solution-processed naphthalene diimides fused with 2-(1,3-dithiol-2-ylidene)malononitrile groups (NDI-DTYM2) that bear branched alkyl chains with varied side-chain length and different branching position, we have carried out systematic studies on the relationship between film microstructure and charge transport in their organic thin-film transistors (OTFTs). In particular synchrotron measurements (grazing incidence X-ray diffraction and near-edge X-ray absorption fine structure) are combined with device optimization studies to probe the interplay between molecular structure, molecular packing, and OTFT mobility. It is found that the side-chain length has a moderate influence on thin-film microstructure but leads to only limited changes in OTFT performance. In contrast, the position of branching point results in subtle, yet critical changes in molecular packing and leads to dramatic differences in electron mobility ranging from ~0.001 to >3.0 cm(2) V(-1) s(-1). Incorporating a NDI-DTYM2 core with three-branched N-alkyl substituents of C(11,6) results in a dense in-plane molecular packing with an unit cell area of 127 Å(2), larger domain sizes of up to 1000 × 3000 nm(2), and an electron mobility of up to 3.50 cm(2) V(-1) s(-1), which is an unprecedented value for ambient stable n-channel solution-processed OTFTs reported to date. These results demonstrate that variation of the alkyl chain branching point is a powerful strategy for tuning of molecular packing to enable high charge transport mobilities.

Polymeric media comprising polybenzimidazoles N-substituted with organic-inorganic hybrid moiety

DOEpatents

Klaehn, John R [Idaho Falls, ID; Peterson, Eric S [Idaho Falls, ID; Wertsching, Alan K [Idaho Falls, ID; Orme, Christopher J [Shelley, ID; Luther, Thomas A [Idaho Falls, ID; Jones, Michael G [Pocatello, ID

2009-12-15

A PBI compound includes imidazole nitrogens at least a portion of which are substituted with an organic-inorganic hybrid moiety may be included in a separator medium. At least 85% of the imidazole nitrogens may be substituted. The organic-inorganic hybrid moiety may be an organosilane moiety, for example, (R)Me.sub.2SiCH.sub.2-- where R is selected from among methyl, phenyl, vinyl, and allyl. The separatory medium may exhibit an H.sub.2, Ar, N.sub.2, O.sub.2, CH.sub.3, or CO.sub.2 gas permeability greater than the gas permeability of a comparable separatory medium comprising the PBI compound without substitution. The separatory medium may further include an electronically conductive medium and/or ionically conductive medium. The separatory medium may be used as a membrane (semi-permeable, permeable, and non-permeable), a barrier, an ion exhcange media, a filter, a gas chromatography coating (such as stationary phase coating in affinity chromatography), etc.

Synthesis of N4-(Substituted phenyl)-N4-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and Identification of New Microtubule Disrupting Compounds that are Effective against Multidrug Resistant Cells1

PubMed Central

Gangjee, Aleem; Zaware, Nilesh; Devambatla, Ravi Kumar Vyas; Raghavan, Sudhir; Westbrook, Cara D.; Dybdal-Hargreaves, Nicholas F.; Hamel, Ernest; Mooberry, Susan L.

2013-01-01

A series of fourteen N4-(substituted phenyl)-N4-methyl/desmethyl-9H-pyrimido[4,5-b]indole-2,4-diamines was synthesized as potential microtubule targeting agents. The synthesis involved a Fisher indole cyclization of 2-amino-6-hydrazinylpyrimidin-4(3H)-one with cyclohexanone, followed by oxidation, chlorination and displacement with appropriate anilines. Compounds 6, 14 and 15 had low nanomolar potency against MDA-MB-435 tumor cells and depolymerized microtubules. Compound 6 additionally had nanomolar GI50 values against 57 of the NCI 60-tumor panel cell lines. Mechanistic studies showed that 6 inhibited tubulin polymerization and [3H]colchicine binding to tubulin. The most potent compounds were all effective in cells expressing P-glycoprotein or the βIII isotype of tubulin, which have been associated with clinical drug reisistence. Modeling studies provided the potential interactions of 6, 14 and 15 within the colchicine site. PMID:23332369

Crystal Structure of a Novel N-Substituted L-Amino Acid Dioxygenase from Burkholderia ambifaria AMMD

PubMed Central

Qin, Hui-Min; Miyakawa, Takuya; Jia, Min Ze; Nakamura, Akira; Ohtsuka, Jun; Xue, You-Lin; Kawashima, Takashi; Kasahara, Takuya; Hibi, Makoto; Ogawa, Jun; Tanokura, Masaru

2013-01-01

A novel dioxygenase from Burkholderia ambifaria AMMD (SadA) stereoselectively catalyzes the C3-hydroxylation of N-substituted branched-chain or aromatic L-amino acids, especially N-succinyl-L-leucine, coupled with the conversion of α-ketoglutarate to succinate and CO2. To elucidate the structural basis of the substrate specificity and stereoselective hydroxylation, we determined the crystal structures of the SadA.Zn(II) and SadA.Zn(II).α-KG complexes at 1.77 Å and 1.98 Å resolutions, respectively. SadA adopted a double-stranded β-helix fold at the core of the structure. In addition, an HXD/EXnH motif in the active site coordinated a Zn(II) as a substitute for Fe(II). The α-KG molecule also coordinated Zn(II) in a bidentate manner via its 1-carboxylate and 2-oxo groups. Based on the SadA.Zn(II).α-KG structure and mutation analyses, we constructed substrate-binding models with N-succinyl-L-leucine and N-succinyl-L-phenylalanine, which provided new insight into the substrate specificity. The results will be useful for the rational design of SadA variants aimed at the recognition of various N-succinyl L-amino acids. PMID:23724013

Reactions of a Ruthenium Complex with Substituted N-Propargyl Pyrroles.

PubMed

Chia, Pi-Yeh; Huang, Shou-Ling; Liu, Yi-Hong; Lin, Ying-Chih

2016-04-05

In an investigation into the chemical reactions of N-propargyl pyrroles 1 a-c, containing aldehyde, keto, and ester groups on the pyrrole ring, with [Ru]-Cl ([Ru]=Cp(PPh3 )2 Ru; Cp=C5 H5 ), an aldehyde group in the pyrrole ring is found to play a crucial role in stimulating the cyclization reaction. The reaction of 1 a, containing an aldehyde group, with [Ru]-Cl in the presence of NH4 PF6 yields the vinylidene complex 2 a, which further reacts with allyl amine to give the carbene complex 6 a with a pyrrolizine group. However, if 1 a is first reacted with allyl amine to yield the iminenyne 8 a, then the reaction of 8 a with [Ru]-Cl in the presence of NH4 PF6 yields the ruthenium complex 9 a, containing a cationic pyrrolopyrazinium group, which has been fully characterized by XRD analysis. These results can be adequately explained by coordination of the triple bond of the propargyl group to the ruthenium metal center first, followed by two processes, that is, formation of a vinylidene intermediate or direct nucleophilic attack. Additionally, the deprotonation of 2 a by R4 NOH yields the neutral acetylide complex 3 a. In the presence of NH4 PF6 , the attempted alkylation of 3 a resulted in the formation the Fischer-type amino-carbene complex 5 a as a result of the presence of NH3, which served as a nucleophile. With KPF6, the alkylation of 3 a with ethyl and benzyl bromoacetates afforded the disubstituted vinylidene complexes 10 a and 11 a, containing ester groups, which underwent deprotonation reactions to give the furyl complexes 12 a and 13 a, respectively. For 13 a, containing an O-benzyl group, subsequent 1,3-migration of the benzyl group was observed to yield product 14 a with a lactone unit. Similar reactivity was not observed for the corresponding N-propargyl pyrroles 1 b and 1 c, which contained keto and ester groups, respectively, on the pyrrole ring. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

N-methylpurine DNA glycosylase inhibits p53-mediated cell cycle arrest and coordinates with p53 to determine sensitivity to alkylating agents

PubMed Central

Song, Shanshan; Xing, Guichun; Yuan, Lin; Wang, Jian; Wang, Shan; Yin, Yuxin; Tian, Chunyan; He, Fuchu; Zhang, Lingqiang

2012-01-01

Alkylating agents induce genome-wide base damage, which is repaired mainly by N-methylpurine DNA glycosylase (MPG). An elevated expression of MPG in certain types of tumor cells confers higher sensitivity to alkylation agents because MPG-induced apurinic/apyrimidic (AP) sites trigger more strand breaks. However, the determinant of drug sensitivity or insensitivity still remains unclear. Here, we report that the p53 status coordinates with MPG to play a pivotal role in such process. MPG expression is positive in breast, lung and colon cancers (38.7%, 43.4% and 25.3%, respectively) but negative in all adjacent normal tissues. MPG directly binds to the tumor suppressor p53 and represses p53 activity in unstressed cells. The overexpression of MPG reduced, whereas depletion of MPG increased, the expression levels of pro-arrest gene downstream of p53 including p21, 14-3-3σ and Gadd45 but not proapoptotic ones. The N-terminal region of MPG was specifically required for the interaction with the DNA binding domain of p53. Upon DNA alkylation stress, in p53 wild-type tumor cells, p53 dissociated from MPG and induced cell growth arrest. Then, AP sites were repaired efficiently, which led to insensitivity to alkylating agents. By contrast, in p53-mutated cells, the AP sites were repaired with low efficacy. To our knowledge, this is the first direct evidence to show that a DNA repair enzyme functions as a selective regulator of p53, and these findings provide new insights into the functional linkage between MPG and p53 in cancer therapy. PMID:22801474

Total Synthesis of (+)-Batzelladine A and (−)-Batzelladine D via [4 + 2]-Annulation of Vinyl Carbodiimides with N-Alkyl Imines

PubMed Central

Arnold, Michael A.; Day, Kenneth A.; Durón, Sergio G.; Gin, David Y.

2008-01-01

A diastereoselective [4 + 2]-annulation of vinyl carbodiimides with chiral N-alkyl imines has been developed to access the stereochemically rich polycyclic guanidine cores of the batzelladine alkaloids. Application of this strategy, together with additional key steps such as long-range directed hydrogenation and diastereoselective intramolecular iodo-amination, led to highly convergent total syntheses of (−)-batzelladine D and (+)-batzelladine A with excellent stereocontrol. PMID:17017806

Prediction of the vapor pressure and vaporization enthalpy of 1-n-alkyl-3-methylimidazolium-bis-(trifluoromethanesulfonyl) amide ionic liquids.

PubMed

Diedenhofen, Michael; Klamt, Andreas; Marsh, Kenneth; Schäfer, Ansgar

2007-09-07

The vapor pressures and vaporization enthalpies of a series of 1-n-alkyl-3-methylimidazolium-bis-(trifluoromethanesulfonyl) amide ionic liquids have been predicted with two different approaches using the COSMO-RS method and quantum chemical gas phase calculations. While the calculated enthalpies are in good agreement with the experimental data, COSMO-RS seems to underestimate the vapor pressures by roughly 0.5-4 log units dependent on the IL and approach used.

Structural Basis of APH(3)-IIIa-Mediated Resistance to N1-Substituted Aminoglycoside Antibiotics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fong, D.; Berghuis, A

2009-01-01

Butirosin is unique among the naturally occurring aminoglycosides, having a substituted amino group at position 1 (N1) of the 2-deoxystreptamine ring with an (S)-4-amino-2-hydroxybutyrate (AHB) group. While bacterial resistance to aminoglycosides can be ascribed chiefly to drug inactivation by plasmid-encoded aminoglycoside-modifying enzymes, the presence of an AHB group protects the aminoglycoside from binding to many resistance enzymes, and hence, the antibiotic retains its bactericidal properties. Consequently, several semisynthetic N1-substituted aminoglycosides, such as amikacin, isepamicin, and netilmicin, were developed. Unfortunately, butirosin, amikacin, and isepamicin are not resistant to inactivation by 3'-aminoglycoside O-phosphotransferase type IIIa [APH(3')-IIIa]. We report here the crystal structuremore » of APH(3')-IIIa in complex with an ATP analog, AMPPNP [adenosine 5'-(?,{gamma}-imido)triphosphate], and butirosin A to 2.4-A resolution. The structure shows that butirosin A binds to the enzyme in a manner analogous to other 4,5-disubstituted aminoglycosides, and the flexible antibiotic-binding loop is key to the accommodation of structurally diverse substrates. Based on the crystal structure, we have also constructed a model of APH(3')-IIIa in complex with amikacin, a commonly used semisynthetic N1-substituted 4,6-disubstituted aminoglycoside. Together, these results suggest a strategy to further derivatize the AHB group in order to generate new aminoglycoside derivatives that can elude inactivation by resistance enzymes while maintaining their ability to bind to the ribosomal A site.« less

Unusual hafnium-pyridylamido/ER(n) heterobimetallic adducts (ER(n) = ZnR2 or AlR3).

PubMed

Rocchigiani, Luca; Busico, Vincenzo; Pastore, Antonello; Talarico, Giovanni; Macchioni, Alceo

2014-02-17

NMR spectroscopy and DFT studies indicate that the Symyx/Dow Hf(IV)-pyridylamido catalytic system for olefin polymerization, [{N(-),N,CNph(-)}HfMe][B(C6F5)4] (1, Nph = naphthyl), interacts with ER(n) (E = Al or Zn, R = alkyl group) to afford unusual heterobimetallic adducts [{N(-),N}HfMe(μ-CNph)(μ-R)ER(n-1)][B(C6F5)4 in which the cyclometalated Nph acts as a bridge between Hf and E. (1)H VT (variable-temperature) EXSY NMR spectroscopy provides direct evidence of reversible alkyl exchanges in heterobimetallic adducts, with ZnR2 showing a higher tendency to participate in this exchange than AlR3. 1-Hexene/ERn competitive reactions with 1 at 240 K reveal that the formation of adducts is strongly favored over 1-hexene polymerization. Nevertheless, a slight increase in the temperature (to >265 K) initiates 1-hexene polymerization. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of alkyl chain length and solvents on thermodynamic dissociation constants of the ionic liquids with one carboxyl group in the alkyl chain of imidazolium cations.

PubMed

Chen, Yuehua; Wang, Huiyong; Wang, Jianji

2014-05-01

Thermodynamic dissociation constants of the Brønsted acidic ionic liquids (ILs) are important for their catalytic and separation applications. In this work, a series of imidazolium bromides with one carboxylic acid substitute group in their alkyl chain ([{(CH2)nCOOH}mim]Br, n = 1,3,5,7) have been synthesized, and their dissociation constants (pKa) at different ionic strengths have been determined in aqueous and aqueous organic solvents at 0.1 mole fraction (x) of ethanol, glycol, iso-propanol, and dimethyl sulfoxide by potentiometric titrations at 298.2 K. The standard thermodynamic dissociation constants (pKa(T)) of the ILs in these solvents were calculated from the extended Debye-Hückel equation. It was found that the pKa values increased with the increase of ionic strength of the media and of the addition of organic solvent in water. The pKa(T) values also increased with the increase of the alkyl chain length of cations of the ILs. In addition, the effect of solvent nature on pKa(T) values is interpreted from solvation of the dissociation components and their Gibbs energy of transfer from water to aqueous organic solutions.

Lithium perchlorate-nitromethane-promoted alkylation of anilines with arylmethanols.

PubMed

Zhou, Jun; Mao, Hai-Feng; Wang, Lu; Zou, Jian-Ping; Zhang, Wei

2011-11-01

A new application of lithium perchlorate-nitromethane (LPNM) for the formation of aromatic C-N and C-C bonds is introduced. LPNM-promoted reactions of anilines with diarylmethanols selectively generate N-alkylated anilines or mono and double Friedel-Crafts alkylation products under different conditions by changing the reaction time, reaction temperature, and the ratio of the reactants. This method does not require the use of transition metal catalysts to prepare alkylated aniline derivatives.

Cysteine Substitution of Transmembrane Domain Amino Acids Alters the Ethanol Inhibition of GluN1/GluN2A N-Methyl-d-Aspartate Receptors

PubMed Central

Xu, Minfu; Smothers, C. Thetford

2015-01-01

N-Methyl-d-aspartate receptors (NMDARs) are inhibited by behaviorally relevant concentrations of ethanol, and residues within transmembrane (TM) domains of NMDARs, including TM3 GluN1 phenylalanine 639 (F639), regulate this sensitivity. In the present study, we used cysteine (C) mutagenesis to determine whether there are additional residues within nearby TM domains that regulate ethanol inhibition on NMDARs. GluN1(F639C)/GluN2A receptors were less inhibited by ethanol than wild-type receptors, and inhibition was restored to wild-type levels following treatment with ethanol-like methanethiosulfonate reagents. Molecular modeling identified six residues in the GluN1 TM1 domain (valine V566; serine S569) and the GluN2A TM4 domain (methionine, M817; V820, F821, and leucine, L824) that were in close vicinity to the TM3 F639 residue, and these were individually mutated to cysteine and tested for ethanol inhibition and receptor function. The F639C-induced decrease in ethanol inhibition was blunted by coexpression of GluN1 TM1 mutants V566C and S569C, and statistically significant interactions were observed for ethanol inhibition among V566C, F639C, and GluN2A TM4 mutants V820C and F821C and S569C, F639C, and GluN2A TM4 mutants F821C and L824C. Ethanol inhibition was also reduced when either GluN1 TM1 mutant V566C or S569C was combined with GluN2A V820C, suggesting a novel TM1:TM4 intrasubunit site of action for ethanol. Cysteines substituted at TM3 and TM4 sites previously suggested to interact with ethanol had less dramatic effects on ethanol inhibition. Overall, the results from these studies suggest that interactions among TM1, TM3, and TM4 amino acids in NMDARs are important determinants of ethanol action at these receptors. PMID:25635140

AN EFFICIENT AQUEOUS N-HETEROCYCLIZATION OF ANILINE DERIVATIVES: MICROWAVE-ASSISTED SYNTHESIS OF N-ARYL AZACYCLOALKANES

EPA Science Inventory

N-aryl azacycloalkanes, an important class of building blocks in natural product and pharmaceuticals, are synthesized via an efficient and simple eco-friendly protocol that involves double N-alkylation of aniline derivatives. The reaction is accelerated by exposure to microwaves ...

Singlet Fission and Excimer Formation in Disordered Solids of Alkyl-Substituted 1,3-Diphenylisobenzofurans.

PubMed

Dron, Paul I; Michl, Josef; Johnson, Justin C

2017-11-16

We describe the preparation and excited state dynamics of three alkyl derivatives of 1,3-diphenylisobenzofuran (1) in both solutions and thin films. The substitutions are intended to disrupt the slip-stacked packing observed in crystals of 1 while maintaining the favorable energies of singlet and triplet for singlet fission (SF). All substitutions result in films that are largely amorphous as judged by the absence of strong X-ray diffraction peaks. The films of 1 carrying a methyl in the para position of one phenyl ring undergo SF relatively efficiently (≥75% triplet yield, Φ T ) but more slowly than thin films of 1. When the methyl is replaced with a t-butyl, kinetic competition in the excited state favors excimer formation rather than SF (Φ T = 55%). When t-Bu groups are placed in both meta positions of the phenyl substituent, SF is slowed further and Φ T = 35%.

Superconductivity and role of pnictogen and Fe substitution in 112-LaPdxP n2 (P n =Sb ,Bi )

NASA Astrophysics Data System (ADS)

Retzlaff, Reiner; Buckow, Alexander; Komissinskiy, Philipp; Ray, Soumya; Schmidt, Stefan; Mühlig, Holger; Schmidl, Frank; Seidel, Paul; Kurian, Jose; Alff, Lambert

2015-03-01

We report on the epitaxial growth of As-free and phase-pure thin films of the 112-pnictide compounds LaPdxP n2 (P n =Sb ,Bi ) grown on (100) MgO substrates by molecular beam epitaxy. X-ray diffraction, reflection high-energy electron diffraction, and x-ray photoelectron spectroscopy confirm the HfCuSi2 structure of the material with a peculiar pnictogen square net layer. The superconducting transition temperature Tc varies little with Pd concentration. LaPdxSb2 has a higher Tc (3.2 K) by about 20% compared with LaPdxBi2 (2.7 K). Fe substitution of Pd leads to a rapid decay of superconductivity, suggesting that these superconductors are conventional type II.

Synthesis of cis-C-Iodo-N-Tosyl-Aziridines using Diiodomethyllithium: Reaction Optimization, Product Scope and Stability, and a Protocol for Selection of Stationary Phase for Chromatography

PubMed Central

2013-01-01

The preparation of C-iodo-N-Ts-aziridines with excellent cis-diastereoselectivity has been achieved in high yields by the addition of diiodomethyllithium to N-tosylimines and N-tosylimine–HSO2Tol adducts. This addition-cyclization protocol successfully provided a wide range of cis-iodoaziridines, including the first examples of alkyl-substituted iodoaziridines, with the reaction tolerating both aryl imines and alkyl imines. An ortho-chlorophenyl imine afforded a β-amino gem-diiodide under the optimized reaction conditions due to a postulated coordinated intermediate preventing cyclization. An effective protocol to assess the stability of the sensitive iodoaziridine functional group to chromatography was also developed. As a result of the judicious choice of stationary phase, the iodoaziridines could be purified by column chromatography; the use of deactivated basic alumina (activity IV) afforded high yield and purity. Rearrangements of electron-rich aryl-iodoaziridines have been promoted, selectively affording either novel α-iodo-N-Ts-imines or α-iodo-aldehydes in high yield. PMID:23738857

Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-Substituted Isoxazolidin-5-ones: Straightforward Access to β2,2 -Amino Acids.

PubMed

Nascimento de Oliveira, Marllon; Arseniyadis, Stellios; Cossy, Janine

2018-04-03

We report here an unprecedented and highly enantioselective palladium-catalyzed allylic alkylation applied to 4-substituted isoxazolidin-5-ones. Ultimately, the process provides a straightforward access to β 2,2 -amino acids bearing an all-carbon quaternary stereogenic center in great yields and a high degree of enantioselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

C2-Selective Branched Alkylation of Benzimidazoles by Rhodium(I)-Catalyzed C-H Activation.

PubMed

Tran, Gaël; Confair, Danielle; Hesp, Kevin D; Mascitti, Vincent; Ellman, Jonathan A

2017-09-01

Herein, we report a Rh(I)/bisphosphine/K 3 PO 4 catalytic system allowing for the first time the selective branched C-H alkylation of benzimidazoles with Michael acceptors. Branched alkylation with N,N-dimethyl acrylamide was successfully applied to the alkylation of a broad range of benzimidazoles incorporating a variety of N-substituents and with both electron-rich and -poor functionality displayed at different sites of the arene. Moreover, the introduction of a quaternary carbon was achieved by alkylation with ethyl methacrylate. The method was also shown to be applicable to the C2-selective branched alkylation of azabenzimidazoles.

Rigid Dipeptide Mimics: Synthesis of Enantiopure 5- and 7-Benzyl and 5,7-Dibenzyl Indolizidinone Amino Acids via Enolization and Alkylation of delta-Oxo alpha,omega-Di-[N-(9-(9-phenylfluorenyl))amino]azelate Esters.

PubMed

Polyak, Felix; Lubell, William D.

1998-08-21

Azabicyclo[X.Y.0]alkane amino acids are tools for constructing mimics of peptide structure and templates for generating combinatorial libraries for drug discovery. Our methodology for synthesizing these conformationally rigid dipeptides has been elaborated such that alkyl groups can be appended onto the heterocycle to generate mimics of peptide backbone and side-chain structure. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/ketone alkylation/reductive amination/lactam cyclization sequence that furnished alkyl-branched azabicyclo[4.3.0]alkane amino acid. Enantiopure 5-benzyl-, 7-benzyl-, and 5,7-dibenzylindolizidinone amino acids 2-4 were stereoselectively synthesized via efficient reaction sequences featuring the alkylation of di-tert-butyl alpha,omega-di-[N-(PhF)amino]azelate delta-ketone 5. A variety of alkyl halides were readily added to the enolate of ketone 5 to provide mono- and dialkylated ketones 6 and 7. Hydride additions to 6 and 7, methanesulfonations, and intramolecular S(N)2 displacements by the PhF amine gave 5-alkylprolines that were converted by lactam cyclizations into 7- and 5-benzyl-, as well as 5,7-dibenzyl-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylate methyl esters 10, 11, and 14. Epimerization of the alkyl-branched stereocenter via an iminium-enaminium equilibrium proved effective for controlling diastereoselectivity in reductive aminations with 6 and 7 in order to furnish 5-alkylprolines that were similarly converted to 7- benzyl- and 5,7-dibenzylindolizidinone N-(BOC)amino esters 10 and 14. Ester hydrolysis with hydroxide ion and potassium trimethylsilanolate then gave enantiopure indolizidinone amino acids 2-4. Epimerization at C-9 of benzylindolizidinone amino esters was also used to provide alternative diastereomers of 10, 11, and 14. This practical methodology for introducing side-chain groups onto the heterocycle with regioselective and diastereoselective control is designed to enhance

Electrophoretic deposition of silicon substituted hydroxyapatite coatings from n-butanol-chloroform mixture.

PubMed

Xiao, Xiu Feng; Liu, Rong Fang; Tang, Xiao Lian

2008-01-01

Silicon Substituted Hydroxyapatite (Si-HA) coatings were prepared on titanium substrates by electrophoretic deposition (EPD). The stability of Si-HA suspension in n-butanol and chloroform mixture has been studied by electricity conductivity and sedimentation test. The microstructure, shear strength and bioactivity in vitro has been tested. The stability of Si-HA suspension containing n-butanol and chloroform mixture as medium is better than that of pure n-butanol as medium. The good adhesion of the particles with the substrate and good cohesion between the particles were obtained in n-butanol and chloroform mixture. Adding triethanolamine (TEA) as additive into the suspension is in favor of the formation of uniform and compact Si-HA coatings on the titanium substrates by EPD. The shear strength of the coatings can reach 20.43 MPa after sintering at 700 degrees C for 2 h, when the volume ratio of n-butanol: chloroform is 2:1 and the concentration of TEA is 15 ml/L. Titanium substrates etched in H(2)O(2)/NH(3) solution help to improve the shear strength of the coatings. After immersion in simulated body fluid for 7 days, Si-HA coatings have the ability to induce the bone-like apatite formation.

Rapid acquisition adaptive amino acid substitutions involved in the virulence enhancement of an H1N2 avian influenza virus in mice.

PubMed

Yu, Zhijun; Sun, Weiyang; Zhang, Xinghai; Cheng, Kaihui; Zhao, Chuqi; Xia, Xianzhu; Gao, Yuwei

2017-08-01

Although H1N2 avian influenza virus (AIV) only infect birds, documented cases of swine infection with H1N2 influenza viruses suggest this subtype AIV may pose a potential threat to mammals. Here, we generated mouse-adapted variants of a H1N2 AIV to identify adaptive changes that increased virulence in mammals. MLD 50 of the variants were reduced >1000-fold compared to the parental virus. Variants displayed enhanced replication in vitro and in vivo, and replicate in extrapulmonary organs. These data show that enhanced replication capacity and expanded tissue tropism may increase the virulence of H1N2 AIV in mice. Sequence analysis revealed multiple amino acid substitutions in the PB2 (L134H, I647L, and D701N), HA (G228S), and M1 (D231N) proteins. These results indicate that H1N2 AIV can rapidly acquire adaptive amino acid substitutions in mammalian hosts, and these amino acid substitutions collaboratively enhance the ability of H1N2 AIV to replicate and cause severe disease in mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

CO2 Reduction Selective for C≥2 Products on Polycrystalline Copper with N-Substituted Pyridinium Additives.

PubMed

Han, Zhiji; Kortlever, Ruud; Chen, Hsiang-Yun; Peters, Jonas C; Agapie, Theodor

2017-08-23

Electrocatalytic CO 2 reduction to generate multicarbon products is of interest for applications in artificial photosynthetic schemes. This is a particularly attractive goal for CO 2 reduction by copper electrodes, where a broad range of hydrocarbon products can be generated but where selectivity for C-C coupled products relative to CH 4 and H 2 remains an impediment. Herein we report a simple yet highly selective catalytic system for CO 2 reduction to C ≥2 hydrocarbons on a polycrystalline Cu electrode in bicarbonate aqueous solution that uses N-substituted pyridinium additives. Selectivities of 70-80% for C 2 and C 3 products with a hydrocarbon ratio of C ≥2 /CH 4 significantly greater than 100 have been observed with several additives. 13 C-labeling studies verify CO 2 to be the sole carbon source in the C ≥2 hydrocarbons produced. Upon electroreduction, the N-substituted pyridinium additives lead to film deposition on the Cu electrode, identified in one case as the reductive coupling product of N -arylpyridinium. Product selectivity can also be tuned from C ≥2 species to H 2 (∼90%) while suppressing methane with certain N-heterocyclic additives.

Lewis acid tuned facial stereodivergent HDA reactions using beta-substituted N-vinyloxazolidinones.

PubMed

Gohier, Frédéric; Bouhadjera, Keltoum; Faye, Djibril; Gaulon, Catherine; Maisonneuve, Vincent; Dujardin, Gilles; Dhal, Robert

2007-01-18

The [4 + 2] acido-catalyzed heterocycloaddition between new beta-substituted N-vinyl-1,3-oxazolidin-2-ones (with R' = Me, Ar, CH2 Ar) and beta,gamma-unsaturated alpha-ketoesters (R = Ar) afforded heteroadducts with high levels of endo and facial selectivities. A complete reversal of facial differentiation was achieved by varying the Lewis acid, leading to the stereoselective formation of either endo-alpha or endo-beta adducts. [reaction: see text].

Ab-initio study of dilute nitride substitutional and split-interstitial impurities in gallium antimonide (N-GaSb)

NASA Astrophysics Data System (ADS)

Jadaun, Priyamvada; Nair, Hari P.; Bank, Seth R.; Banerjee, Sanjay K.

2012-02-01

We present an ab-initio density functinal theory study of dilute-nitride GaSb. Adding dilute quantities of nitrogen causes rapid reduction in bandgap of GaSb (˜300 meV for 2% N). Due to this rapid reduction in bandgap, dilute-nitrides provide a pathway for extending the emission of GaSb based type-I diode lasers into the mid-infrared wavelength region (3-5 micron). In this study we look at the effect of substitutional N impurity on the electronic properties of our system and compare it with the band-anticrossing model, a phenomenological model, which has been used to explain giant band bowing observed in dilute-nitride alloys. We also study the effect of Sb-N split interstitials which are known to be non-radiative recombination centers. Furthermore we also discuss the stability of the Sb-N split interstitial relative to substitutional nitrogen to determine if the split interstitials can be annihilated using post-growth annealing to improve the radiative lifetime of the material which essential for laser operation.

Cu-catalyzed aerobic oxidative cyclizations of 3-N-hydroxyamino-1,2-propadienes with alcohols, thiols, and amines to form α-O-, S-, and N-substituted 4-methylquinoline derivatives.

PubMed

Sharma, Pankaj; Liu, Rai-Shung

2015-03-16

A one-pot, two-step synthesis of α-O-, S-, and N-substituted 4-methylquinoline derivatives through Cu-catalyzed aerobic oxidations of N-hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N-hydroxyaminoallenes with NuH (Nu = OH, OR, NHR, and SR) to form 3-substituted 2-en-1-ones, followed by Brønsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical-type mechanism rather than a typical nitrone-intermediate route. The utility of this new Cu-catalyzed reaction is shown by its applicability to the synthesis of several 2-amino-4-methylquinoline derivatives, which are known to be key precursors to several bioactive molecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new acylamidase from Rhodococcus erythropolis TA37 can hydrolyze N-substituted amides.

PubMed

Lavrov, K V; Zalunin, I A; Kotlova, E K; Yanenko, A S

2010-08-01

A new acylamidase was isolated from Rhodococcus erythropolis TA37 and characterized. N-Substituted acrylamides (isopropyl acrylamide, N,N-dimethyl-aminopropyl acrylamide, and methylene-bis-acrylamide), acid para-nitroanilides (4'-nitroacetanilide, Gly-pNA, Ala-pNA, Leu-pNA), and N-acetyl derivatives of glycine, alanine, and leucine are good substrates for this enzyme. Aliphatic amides (acetamide, acrylamide, isobutyramide, n-butyramide, and valeramide) are also used as substrates but with less efficiency. The enzyme subunit mass by SDS-PAGE is 55 kDa. Maximal activity is exhibited at pH 7-8 and 55°C. The enzyme is stable for 15 h at 22°C and for 0.5 h at 45°C. The Michaelis constant (K(m)) is 0.25 mM with Gly-pNA and 0.55 mM with Ala-pNA. The acylamidase activity is suppressed by inhibitors of serine proteases (phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate) but is not suppressed by inhibitors of aliphatic amidases (acetaldehyde and nitrophenyl disulfides). The N-terminal amino acid sequence of the acylamidase is highly homologous to those of two putative amidases detected from sequenced R. erythropolis genomes. It is suggested that the acylamidase together with the detected homologs forms a new class within the amidase signature family.

N-Methylamino Pyrimidyl Amides (MAPA): Highly Reactive, Electronically-Activated Amides in Catalytic N-C(O) Cleavage.

PubMed

Meng, Guangrong; Lalancette, Roger; Szostak, Roman; Szostak, Michal

2017-09-01

Despite recent progress in catalytic cross-coupling technologies, the direct activation of N-alkyl-N-aryl amides has been a challenging transformation. Here, we report the first Suzuki cross-coupling of N-methylamino pyrimidyl amides (MAPA) enabled by the controlled n N → π Ar conjugation and the resulting remodeling of the partial double bond character of the amide bond. The new mode of amide activation is suitable for generating acyl-metal intermediates from unactivated primary and secondary amides.

Extending the cleavage rules for the hammerhead ribozyme: mutating adenosine15.1 to inosine15.1 changes the cleavage site specificity from N16.2U16.1H17 to N16.2C16.1H17.

PubMed Central

Ludwig, J; Blaschke, M; Sproat, B S

1998-01-01

In this paper, we show that an adenosine to inosine mutation at position 15.1 changes the substrate specificity of the hammerhead ribozyme from N16.2U16.1H17to N16.2C16.1H17(H represents A, C or U). This result extends the hammerhead cleavage triplet definition from N16.2U16.1H17to the more general N16.2Y16.1H17. Comparison of cleavage rates using I15.1ribozymes for NCH triplets and standard A15.1 ribozymes for NUH triplets under single turnover conditions shows similar or slightly enhanced levels of reactivity for the I15. 1-containing structures. The effect of I15.1 substitution was also tested in nuclease-resistant 2'- O -alkyl substituted derivatives (oligozymes), showing a similar level of activity for the NUH and NCH cleaving structures. The availability of NCH triplets that can be targeted without loss of efficiency increases the flexibility of ribozyme targeting strategies. This was demonstrated by an efficient cleavage of an HCV transcript at a previously inaccessible GCA site in codon 2. PMID:9580675

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

PubMed Central

Chattopadhyay, Kalicharan; Fenster, Erik; Grenning, Alexander J

2012-01-01

Summary The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening. PMID:23019448

Identification of Substituted Pyrimido[5,4-b]indoles as Selective Toll-Like Receptor 4 Ligands

PubMed Central

2013-01-01

A cell-based high-throughput screen to identify small molecular weight stimulators of the innate immune system revealed substituted pyrimido[5,4-b]indoles as potent NFκB activators. The most potent hit compound selectively stimulated Toll-like receptor 4 (TLR4) in human and mouse cells. Synthetic modifications of the pyrimido[5,4-b]indole scaffold at the carboxamide, N-3, and N-5 positions revealed differential TLR4 dependent production of NFκB and type I interferon associated cytokines, IL-6 and interferon γ-induced protein 10 (IP-10) respectively. Specifically, a subset of compounds bearing phenyl and substituted phenyl carboxamides induced lower IL-6 release while maintaining higher IP-10 production, skewing toward the type I interferon pathway. Substitution at N-5 with short alkyl substituents reduced the cytotoxicity of the leading hit compound. Computational studies supported that active compounds appeared to bind primarily to MD-2 in the TLR4/MD-2 complex. These small molecules, which stimulate innate immune cells with minimal toxicity, could potentially be used as adjuvants or immune modulators. PMID:23656327

In vitro cytotoxicity and differential cellular sensitivity of derivatives of diamino acids. II. N1-methyl, N1-allyl, N1-(2-chloroethyl) and N1-propargyl nitrosoureas.

PubMed

Dulude, H; Salvador, R; Gallant, G

1995-01-01

The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-methyl, N1-allyl, N1-2-chloroethyl and N1-propargyl nitrosourea derivatives of diamino acids were determined in the National Cancer Institute's primary antitumor drug screen. The compounds tested showed an in vitro anticancer activity similar to commercialized nitrosoureas such as CCNU, BCNU, MeCCNU, chlorozotocin, streptozotocin and PCNU. The alkylating moiety of the nitrosoureas seems to play a role in the general selectivity of our compounds. The N1-methyl and N1-2-chloroethyl nitrosourea derivatives are more selective for central nervous system cell lines, the N1-allyl nitrosourea derivatives are more selective for lung cancer cell lines and the N1-propargyl nitrosoureas are more selective for leukemia cell lines.

N-substituted imidazolines and ethylenediamines and their action on alpha- and beta-adrenergic receptors.

PubMed

Hamada, A; Yaden, E L; Horng, J S; Ruffolo, R R; Patil, P N; Miller, D D

1985-09-01

A series of N-substituted imidazolines and ethylenediamines were synthesized and examined for their activity in alpha- and beta-adrenergic systems. The length of the intermediate side chain between the catechol and imidazoline ring or the amine of the ethylenediamine segment was shown to affect the adrenergic activity. N-[2-(3,4-Dihydroxyphenyl)ethyl]imidazoline hydrochloride (2) and N-[2-(3,4-dihydroxyphenyl)ethyl]ethylenediamine dihydrochloride (4), both with two methylene groups between the catechol and amine segment, were found to be somewhat selective for alpha 2-adrenergic receptors while 1-(3,4-dihydroxybenzyl)imidazoline hydrochloride (1) and N-2-(3,4-dihydroxybenzyl)ethylenediamine dihydrochloride (3), both with one methylene group between the catechol and amine segment, were more selective for alpha1-adrenergic receptors in a pithed rat model. Of the four compounds examined, only compound 2 showed significant direct activity on beta1- and beta2-adrenergic receptors.

Analytical characterization of seventeen ring-substituted N,N-diallyltryptamines

PubMed Central

Brandt, Simon D.; Kavanagh, Pierce V.; Dowling, Geraldine; Talbot, Brian; Westphal, Folker; Meyer, Markus R.; Maurer, Hans H.; Halberstadt, Adam L.

2017-01-01

Many N,N-dialkylated tryptamines show psychoactive properties in humans and the number of derivatives involved in multidisciplinary areas of research has grown over the last few decades. Whereas some derivatives form the basis of a range of medicinal products, others are predominantly encountered as recreational drugs, and in some cases, the areas of therapeutic and recreational use can overlap. In recent years, 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) has appeared as a new psychoactive substance (NPS) and ‘research chemical’ whereas 4-acetoxy-DALT and the ring-unsubstituted DALT have only been detected very recently. Strategies pursued in the authors’ laboratories included the preparation and biological evaluation of previously unreported N,N-diallyltryptamines (DALTs). This report describes the analytical characterization of seventeen DALTs. Fifteen DALTs were prepared by a microwave-accelerated Speeter and Anthony procedure following established procedures developed previously in the authors’ laboratories. In addition to DALT, the substances included in this study were 2-phenyl-, 4-acetoxy-, 4-hydroxy-, 4,5-ethylenedioxy-, 5-methyl-, 5-methoxy-, 5-methoxy-2-methyl-, 5-ethoxy-, 5-fluoro-, 5-fluoro-2-methyl-, 5-chloro-, 5-bromo-, 5,6-methylenedioxy-, 6-fluoro-, 7-methyl, and 7-ethyl-DALT, respectively. The DALTs were characterized by nuclear magnetic resonance spectroscopy (NMR), gas chromatography (GC) quadrupole and ion trap (EI/CI) mass spectrometry (MS), low and high mass accuracy MS/MS, ultraviolet diode array detection and GC solid-state infrared analysis, respectively. A comprehensive collection of spectral data was obtained that are provided to research communities who face the challenge of encountering newly emerging substances where analytical data are not available. These data are also relevant to researchers who might wish to explore the clinical and non-clinical uses of these substances. PMID:27100373

Thermoelectric properties of n-type double substituted SrTiO3 bulk materials.

PubMed

Cui, Yanjie; He, Jian; Amow, Gisele; Kleinke, Holger

2010-01-28

A series of La, Ta double substituted Sr(1-x)La(x)Ti(1-x)Ta(x)O(3), with x = 0.01, 0.05 and 0.10, and La, Nb double substituted Sr(0.90)La(0.10)Ti(0.90)Nb(0.10)O(3) for comparison were investigated in this project. Rietveld refinements were performed to check for purity and symmetry reduction. Electronic structure calculations indicate n-type conduction with steep and flat bands in the vicinity of the Fermi level for x = 0.125. Seebeck coefficient, electrical conductivity, and thermal conductivity measurements on hot-pressed and spark-plasma-sintered samples were performed over a wide range of temperatures. Best results were obtained by spark-plasma-sintering of double substituted Sr(0.99)La(0.01)Ti(0.99)Ta(0.01)O(3) with a thermoelectric figure-of-merit of 0.13 at 660 K.

Reduced DNA repair in mouse satellite DNA after treatment with methylmethanesulfonate, and N-methyl-N-nitrosourea.

PubMed Central

Bodell, W J; Banerjee, M R

1976-01-01

We have measured DNA repair in mouse satellite and main band DNA as resolved by Ag+-Cs2SO4 centrifugation in response to treatment with the alkylating agents, methyl methanesulfonate, and N-methyl-N-nitrosourea. We find that there is a statistically significant lower incorporation of 3H-Tdr into the satellite DNA as compared to the main band at varying periods after treatment with the alkylating agents. This suggests a reduced repair activity in the satellite DNA. We have measured the extent of binding of 14C-methyl methanesulfonate to the satellite, and main band DNA, and no difference in binding was observed, indicating that the reduced repair activity of satellite DNA is not due to a difference in binding of alkylating agents. We believe that the reduced incorporation of 3H-Tdr into satellite DNA may be due to its location in the condensed chromatin fraction. PMID:184436

Exploring High-Performance n-Type Thermoelectric Composites Using Amino-Substituted Rylene Dimides and Carbon Nanotubes.

PubMed

Wu, Guangbao; Zhang, Zhi-Guo; Li, Yongfang; Gao, Caiyan; Wang, Xin; Chen, Guangming

2017-06-27

Taking advantage of the high electrical conductivity of a single-walled carbon nanotube (SWCNT) and the large Seebeck coefficient of rylene diimide, a convenient strategy is proposed to achieve high-performance n-type thermoelectric (TE) composites containing a SWCNT and amino-substituted perylene diimide (PDINE) or naphthalene diimide (NDINE). The obtained n-type composites display greatly enhanced TE performance with maximum power factors of 112 ± 8 (PDINE/SWCNT) and 135 ± 14 (NDINE/SWCNT) μW m -1 K -2 . A short doping time of 0.5 h can ensure high TE performance. The corresponding TE module consisting of five p-n junctions reaches a large output power of 3.3 μW under a 50 °C temperature gradient. In addition, the n-type composites exhibit high air stability and excellent thermal stability. This design strategy benefits the future fabricating of high-performance n-type TE materials and devices.

C- and N-Metalated Nitriles: The Relationship between Structure and Selectivity.

PubMed

Yang, Xun; Fleming, Fraser F

2017-10-17

Metalated nitriles are exceptional nucleophiles capable of forging highly hindered stereocenters in cases where enolates are unreactive. The excellent nucleophilicity emanates from the powerful inductive stabilization of adjacent negative charge by the nitrile, which has a miniscule steric demand. Inductive stabilization is the key to understanding the reactivity of metalated nitriles because this permits a continuum of structures that range from N-metalated ketenimines to nitrile anions. Solution and solid-state analyses reveal two different metal coordination sites, the formally anionic carbon and the nitrile nitrogen, with the site of metalation depending intimately on the solvent, counterion, temperature, and ligands. The most commonly encountered structures, C- and N-metalated nitriles, have either sp 3 or sp 2 hybridization at the nucleophilic carbon, which essentially translates into two distinct organometallic species with similar but nonidentical stereoselectivity, regioselectivity, and reactivity preferences. The hybridization differences are particularly important in S N i displacements of cyclic nitriles because the orbital orientations create very precise trajectories that control the cyclization selectivity. Harnessing the orbital differences between C- and N-metalated nitriles allows selective cyclization to afford nitrile-containing cis- or trans-hydrindanes, decalins, or bicyclo[5.4.0]undecanes. Similar orbital constraints favor preferential S N i displacements with allylic electrophiles on sp 3 centers over sp 2 centers. The strategy permits stereoselective displacements on secondary centers to set contiguous tertiary and quaternary stereocenters or even contiguous vicinal quaternary centers. Stereoselective alkylations of acyclic nitriles are inherently more challenging because of the difficulty in creating steric differentiation in a dynamic system with rotatable bonds. However, judicious substituent placement of vicinal dimethyl groups and a

Alkylation of a bioinspired high spin Ni(II)N{sub 3}S{sub 2} complex with bifunctional reagents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chohan, B. S., E-mail: bsc12@psu.edu

2013-12-15

Crystal structures of two S-alkylated complexes generated from the reaction of iodoacetamide and iodoethanol with an air and moisture sensitive high spin Ni(II) pentacoordinate triaminodithiolate complex, 1 are determined by X-ray structure analysis. Crystals of complex 2, [NiC{sub 16}H{sub 31}N{sub 5}O{sub 2}S{sub 2}]I{sub 2}, are triclinic, sp. gr. P-bar1 , Z = 2. Crystals of complex 3, [NiC{sub 16}H{sub 28}N{sub 3}O{sub 2}S{sub 2}]I{sub 2}, are monoclinic, sp. gr. P2{sub 1}/c, Z = 4. Structures of complexes 2 and 3 are very similar: one of the S-acetamide (2) or S-ethanol (3) groups coordinates to the Ni center through the oxygen atom formingmore » N{sub 3}S{sub 2}O hexacoordination; the other group remains unbound to the Ni and left dangling. Crystal packing shows that complexes 2 and 3 interact with the iodide counterions, and that only complex 2 interact with neighboring molecules; some of these close intermolecular contacts include H-bonding interactions.« less

Small angle neutron scattering from 1-alkyl-3-methylimidazolium hexafluorophosphate ionic liquids ([Cnmim][PF6], n=4, 6, and 8)

NASA Astrophysics Data System (ADS)

Hardacre, Christopher; Holbrey, John D.; Mullan, Claire L.; Youngs, Tristan G. A.; Bowron, Daniel T.

2010-08-01

The presence of local anisotropy in the bulk, isotropic, and ionic liquid phases—leading to local mesoscopic inhomogeneity—with nanoscale segregation and expanding nonpolar domains on increasing the length of the cation alkyl-substituents has been proposed on the basis of molecular dynamics (MD) simulations. However, there has been little conclusive experimental evidence for the existence of intermediate mesoscopic structure between the first/second shell correlations shown by neutron scattering on short chain length based materials and the mesophase structure of the long chain length ionic liquid crystals. Herein, small angle neutron scattering measurements have been performed on selectively H/D-isotopically substituted 1-alkyl-3-methylimidazolium hexafluorophosphate ionic liquids with butyl, hexyl, and octyl substituents. The data show the unambiguous existence of a diffraction peak in the low-Q region for all three liquids which moves to longer distances (lower Q), sharpens, and increases in intensity with increasing length of the alkyl substituent. It is notable, however, that this peak occurs at lower values of Q (longer length scale) than predicted in any of the previously published MD simulations of ionic liquids, and that the magnitude of the scattering from this peak is comparable with that from the remainder of the amorphous ionic liquid. This strongly suggests that the peak arises from the second coordination shells of the ions along the vector of alkyl-chain substituents as a consequence of increasing the anisotropy of the cation, and that there is little or no long-range correlated nanostructure in these ionic liquids.

Bis(thienothiophenyl) diketopyrrolopyrrole-based conjugated polymers with various branched alkyl side chains and their applications in thin-film transistors and polymer solar cells.

PubMed

Shin, Jicheol; Park, Gi Eun; Lee, Dae Hee; Um, Hyun Ah; Lee, Tae Wan; Cho, Min Ju; Choi, Dong Hoon

2015-02-11

New thienothiophene-flanked diketopyrrolopyrrole and thiophene-containing π-extended conjugated polymers with various branched alkyl side-chains were successfully synthesized. 2-Octyldodecyl, 2-decyltetradecyl, 2-tetradecylhexadecyl, 2-hexadecyloctadecyl, and 2-octadecyldocosyl groups were selected as the side-chain moieties and were anchored to the N-positions of the thienothiophene-flanked diketopyrrolopyrrole unit. All five polymers were found to be soluble owing to the bulkiness of the side chains. The thin-film transistor based on the 2-tetradecylhexadecyl-substituted polymer showed the highest hole mobility of 1.92 cm2 V(-1) s(-1) due to it having the smallest π-π stacking distance between the polymer chains, which was determined by grazing incidence X-ray diffraction. Bulk heterojunction polymer solar cells incorporating [6,6]-phenyl-C71-butyric acid methyl ester as the n-type molecule and the additive 1,8-diiodooctane (1 vol %) were also constructed from the synthesized polymers without thermal annealing; the device containing the 2-octyldodecyl-substituted polymer exhibited the highest power conversion efficiency of 5.8%. Although all the polymers showed similar physical properties, their device performance was clearly influenced by the sizes of the branched alkyl side-chain groups.

Assembly of N,N-disubstituted hydrazines and 1-aryl-1H-indazoles via copper-catalyzed coupling reactions.

PubMed

Xiong, Xiaodong; Jiang, Yongwen; Ma, Dawei

2012-05-18

CuI-catalyzed coupling of N-acyl-N'-substituted hydrazines with aryl iodides takes place at 60-90 °C to afford N-acyl-N',N'-disubstituted hydrazines regioselectively and thereby gives a facile method for assembling N,N-diaryl hydrazines. N-Acyl-N'-substituted hydrazines can also react with 2-bromoarylcarbonylic compounds at 60-125 °C under the catalysis of CuI/4-hydroxy-l-proline to provide 1-aryl-1H-indazoles.

Inhibition by Avibactam and Clavulanate of the β-Lactamases KPC-2 and CTX-M-15 Harboring the Substitution N132G in the Conserved SDN Motif.

PubMed

Ourghanlian, Clément; Soroka, Daria; Arthur, Michel

2017-03-01

The substitution N 132 G in the SDN motif of class A β-lactamases from rapidly growing mycobacteria was previously shown to impair their inhibition by avibactam but to improve the stability of acyl-enzymes formed with clavulanate. The same substitution was introduced in KPC-2 and CTX-M-15 to assess its impact on β-lactamases from Enterobacteriaceae and evaluate whether it may lead to resistance to the ceftazidime-avibactam combination. Kinetic parameters for the inhibition of the β-lactamases by avibactam and clavulanate were determined by spectrophotometry using nitrocefin as the substrate. The substitution N 132 G impaired (>1,000-fold) the efficacy of carbamylation of KPC-2 and CTX-M-15 by avibactam. The substitution improved the inhibition of KPC-2 by clavulanate due to reduced deacylation, whereas the presence or absence of N 132 G resulted in the inhibition of CTX-M-15 by clavulanate. The hydrolysis of amoxicillin and nitrocefin by KPC-2 and CTX-M-15 was moderately affected by the substitution N 132 G, but that of ceftazidime, ceftaroline, and aztreonam was drastically reduced. Isogenic strains producing KPC-2 and CTX-M-15 were constructed to assess the impact of the substitution N 132 G on the antibacterial activities of β-lactam-inhibitor combinations. For amoxicillin, the substitution resulted in resistance and susceptibility for avibactam and clavulanate, respectively. For ceftazidime, ceftaroline, and aztreonam, the negative impact of the substitution on β-lactamase activity prevented resistance to the β-lactam-avibactam combinations. In conclusion, the N 132 G substitution has profound effects on the substrate and inhibition profiles of class A β-lactamases, which are largely conserved in distantly related enzymes. Fortunately, the substitution does not lead to resistance to the ceftazidime-avibactam combination. Copyright © 2017 American Society for Microbiology.

New carbocyclic N(6)-substituted adenine and pyrimidine nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, antiviral, anticancer activity and X-ray crystallography.

PubMed

Tănase, Constantin I; Drăghici, Constantin; Cojocaru, Ana; Galochkina, Anastasia V; Orshanskaya, Jana R; Zarubaev, Vladimir V; Shova, Sergiu; Enache, Cristian; Maganu, Maria

2015-10-01

New nucleoside analogues with an optically active bicyclo[2.2.1]heptane skeleton as sugar moiety and 6-substituted adenine were synthesized by alkylation of 6-chloropurine intermediate. Thymine and uracil analogs were synthesized by building the pyrimidine ring on amine 1. X-ray crystallography confirmed an exo-coupling of the thymine to the ring and an L configuration of the nucleoside analogue. The library of compounds was tested for their inhibitory activity against influenza virus A∖California/07/09 (H1N1)pdm09 and coxsackievirus B4 in cell culture. Compounds 13a and 13d are the most promising for their antiviral activity against influenza, and compound 3c against coxsackievirus B4. Compounds 3b and 3g were tested for anticancer activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

"CH"/N substituted mer-Gaq3 and mer-Alq3 derivatives: an effective approach for the tuning of emitting color.

PubMed

Gahungu, Godefroid; Zhang, Jingping

2005-09-22

Equilibrium geometry configurations of the "CH"/N substituted Alq3 and Gaq3 derivatives are calculated by density functional theory (B3LYP/6-31G). The frontier molecular orbital and gap energy calculations for all complexes have been performed at the HF/6-31G level. It was shown that, compared to the pristine molecules, the HOMO and LUMO are stabilized, the net effect being however an increasing/decreasing of the gap (Eg) depending on the position of the substituted group. On the basis of the equilibrium geometries, the effect of the substitution on the absorption and emission spectra was evaluated using TDB3LYP/3-21G. It was shown that the change of "CH"/N substituted position on 8-hydroxyquinoline ligand is a powerful approach for the tuning of emitting color. An important blue shift was predicted for 5-substituted 8-hydroxyquinoline derivatives, an important red one being observed for 4-substituted ones. Interestingly, relatively significant blue and red shifts were also predicted for the 7- and 2-substituted derivatives. In this work, the correlation between the spectrum shifts and the metal-ligand bonding is also discussed.

Mechanism of Surface Alkylation of a Gold Aerogel with Tetra-n-butylstannane-d36: Identification of Byproducts.

PubMed

Benkovičová, Monika; Wen, Dan; Plutnar, Jan; Čížková, Martina; Eychmüller, Alexander; Michl, Josef

2017-05-18

The formation of self-assembled monolayers on surfaces is often likely to be accompanied by the formation of byproducts, whose identification holds clues to the reaction mechanism but is difficult due to the minute amounts produced. We now report a successful identification of self-assembly byproducts using gold aerogel with a large specific surface area, a procedure likely to be applicable generally. Like a thin gold layer on a flat substrate, the aerogel surface is alkylated with n-butyl-d 9 groups upon treatment with a solution of tetra-n-butylstannane-d 36 under ambient conditions. The reaction byproducts accumulate in the mother liquor in amounts sufficient for GC-MS analysis. In chloroform solvent, they are butene-d 8 , butane-d 10 , octane-d 18 , and tributylchlorostannane-d 27 . In hexane, they are the same except that tributylchlorostannane-d 27 is replaced with hexabutyldistannane-d 54 . The results are compatible with an initial homolytic dissociation of a C-Sn bond on the gold surface, followed by known radical processes.

Substitution Effects and Linear Free Energy Relationships During Reduction of 4- Benzoyl-n-(4-substituted Benzyl)pyridinium Cations

NASA Technical Reports Server (NTRS)

Leventis, Nicholas; Zhang, Guo-Hui; Rawashdeh, Abdel-Monem M.; Sotiriou-Leventis, Chariklia; Gray, Hugh R. (Technical Monitor)

2003-01-01

In analogy to 4-(para-substituted benzoyl)-N-methylpyridinium cations (1-X's), the title species (2-X's, -X = -OCH3, -CH3, -H, -Br, -COCH3, -NO2) undergo two reversible, well-separated (E(sub 1/2) greater than or equal to 650 mV) one-electron reductions. The effect of substitution on the reduction potentials of 2-X's is much weaker than the effect of the same substituents on 1-X's: the Hammett rho-values are 0.80 and 0.93 for the 1st- and 2nd-e reduction of 2-X's vs. 2.3 and 3.3 for the same reductions of 1-X's, respectively. Importantly, the nitro group of 2-NO2 undergoes reduction before the 2nd-e reduction of the 4-benzoylpyridinium system. These results suggest that the redox potentials of the 4-benzoylpyridinium system can be course-tuned via p-benzoyl substitution and fine-tuned via para-benzyl substitution. Introducing the recently derived substituent constant of the -NO2(sup)- group (sigma para-NO2(sup)- = -0.97) yields an excellent correlation for the 3rd-e reduction of 2- NO2 (corresponding to the reduction of the carbonyl group) with the 2nd-e reduction of the other 2-X's, and confirms the electron donating properties of -NO2(sup)-.

Palladium-catalyzed one-pot three- or four-component coupling of aryl iodides, alkynes, and amines through C-N bond cleavage: efficient synthesis of indole derivatives.

PubMed

Hao, Wei; Geng, Weizhi; Zhang, Wen-Xiong; Xi, Zhenfeng

2014-02-24

An efficient synthesis of N-substituted indole derivatives was realized by combining the Pd-catalyzed one-pot multicomponent coupling approach with cleavage of the C(sp(3))-N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene-phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1-bromo-2-iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4-methylpiperidine, 1-methylpiperazine, 2-methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3-b]indole. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-assembled structures of N-alkylated bisbenzimidazolyl naphthalene in aqueous media for highly sensitive detection of picric acid.

PubMed

Wu, Yan-Cheng; Luo, Shi-He; Cao, Liang; Jiang, Kai; Wang, Ling-Yun; Xie, Jie-Chun; Wang, Zhao-Yang

2017-07-11

A 2,6-dibenzimidazole-appended naphthalene derivative flanking with two N-alkyl chains (sensor 4) was designed and applied for highly sensitive detection of picric acid (PA) in aqueous media. Driven by the hydrophobicity of alkyl chain and π-π stacking effect of aryl, sensor 4 can undergo self-assembly to form an orderly rod-like structure in H 2 O/THF (v/v, 90/10) solution, as shown by the dynamic light scattering (DLS) and scanning electron microscopy (SEM) studies. Sensor 4 shows high selectivity and sensitivity toward PA over other nitroaromatic explosives. DFT calculations and 1 H NMR, the time-correlated single photon counting (TCSPC) experiments confirm that the quenching mechanism is due to both electron and energy transfer from the electron-rich sensor 4 to the electron-deficient PA. Sensor 4 can detect as low as 0.57 ppb PA in aqueous media and 11.46 ag cm -2 PA by contact mode. Importantly, sensor 4 exhibits low interference against common solvents, metal ions and anions. Thus, it is practically applicable for sensing PA in real environmental samples and vapor phase. Copyright © 2017 Elsevier B.V. All rights reserved.

Anhydrous versus hydrated N4-substituted 1H-pyrazolo[3,4-d]pyrimidine-4,6-diamines: hydrogen bonding in two and three dimensions.

PubMed

Trilleras, Jorge; Quiroga, Jairo; Cobo, Justo; Marchal, Antonio; Nogueras, Manuel; Low, John N; Glidewell, Christopher

2008-10-01

Ten new N(4)-substituted 1H-pyrazolo[3,4-d]pyrimidine-4,6-diamines have been synthesized and the structures of nine of them are reported here, falling into two clear groups, those which are stoichiometric hydrates and those which crystallize in solvent-free forms. In each of N(4)-methyl-N(4)-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine, C(12)H(12)N(6) (I), N(4)-cyclohexyl-N(4)-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine, C(12)H(18)N(6) (II), and N(4)-(3-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine, C(11)H(9)ClN(6) (III), the molecules are linked into hydrogen-bonded sheets. The molecules of 2-{4-(6-amino-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl}ethanol, C(11)H(17)N(7)O (IV), are linked into a three-dimensional framework, while the structure of N(4)-methyl-N(4)-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine monohydrate, C(13)H(14)N(6) x H(2)O (V), is only two-dimensional despite the presence of five independent hydrogen bonds. The stoichiometric hemihydrates N(4)-ethyl-N(4)-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine hemihydrate, C(13)H(14)N(6) x 0.5 H(2)O (VI) and N(4)-(4-methoxyphenyl)-N(4)-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine hemihydrate, C(13)H(14)N(6)O x 0.5 H(2)O (VII), exhibit remarkably similar sheet structures, despite different space groups and Z' values, Z' = 0.5 in C2/c for (VI) and Z' = 1 in P1 for (VII). N(4)-4-Benzyl-N(4)-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine monohydrate, C(18)H(16)N(6) x H(2)O (VIII), crystallizes with Z' = 2 in P2(1)/n, and the four independent molecular components are linked into sheets by a total of 11 intermolecular hydrogen bonds. The sheet structure in {4-(pyrrolidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine-6-amine} ethanol hemisolvate hemihydrate, C(9)H(12)N(6).0.5C(2)H(6)O x 0.5 H(2)O (IX), is built from the pyrimidine and water components only; it contains eight independent hydrogen bonds, and it very closely mimics the sheets in (VI) and (VII); the ethanol molecules are

Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes.

PubMed

Trost, Barry M; Bai, Wen-Ju; Hohn, Christoph; Bai, Yu; Cregg, James J

2018-05-30

Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1 H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.

Conformational analysis of some N,N-diethyl-2-[(4‧-substituted) phenylthio] acetamides

NASA Astrophysics Data System (ADS)

Vinhato, Elisângela; Olivato, Paulo R.; Zukerman-Schpector, Julio; Dal Colle, Maurizio

2013-11-01

The conformational analysis of some N,N-diethyl-2[(4‧-substituted)phenylthio]acetamides bearing the substituents OMe 1, Me 2, H 3, Cl 4, Br 5 and NO26, was performed by νCO IR analysis, along with B3LYP/6-311++G(d,p) and Polarisable Continuum Model (PCM) calculations, as well as NBO analysis for 1, 3, and 6 and X-ray diffraction for 4. The results of the calculations indicated the existence of two stable conformation pairs, i.e. gauche (anti; syn) (most stable) and cis (anti; syn) in the gas phase. The gauche conformers were less polar with respect to the cis ones for 1 and 3, but more polar for 6. The most intense IR carbonyl doublet component observed at the lower frequency can be ascribed to the gauche conformers g(anti; syn) for 3-6 in n-C6H14, which is in agreement with the gauche and cis relative stabilities and frequencies resulting from the PCM calculations. Similarly, the single IR band for 1 and 2 in n-hexane may be attributed to the gauche conformers. The PCM calculations compared well with the IR data for the compounds in solution, showing that there is a progressive increase of the cis/gauche population ratio as the solvent polarity increases. The NBO analysis indicated that the gauche(anti; syn) conformation in the gas phase was stabilized by the relevant LPS4 → πC 2dbnd O 1∗, πC 2dbnd O 1 → σC 3sbnd S 4∗ , σC 3sbnd S 4 → πC 2dbnd O 1∗, πC 2dbnd O 1∗ → σC 3sbnd S 4∗, and LPO1 →σ∗ C11sbnd H28 orbital interactions, which were absent in the cis(anti; syn) conformer. On the contrary, the cis conformer for derivatives 1, 3, and 6 were stabilized by the σC 3 -S 4∗ →σ∗ C2sbnd N5 orbital interaction (through bond coupling), along with the additional LPO1 →σ∗ S4sbnd C10 interaction for 6. Moreover, the electrostatic repulsion between the Cδ+sbnd Sδ- and Cδ+dbnd Oδ- dipoles (Repulsive Field Effect) contributed to both the larger destabilization and increase of the νCO frequency of the cis conformer with respect

Reactivities of Substituted α-Phenyl-N-tert-butyl Nitrones

PubMed Central

2015-01-01

In this work, a series of α-phenyl-N-tert-butyl nitrones bearing one, two, or three substituents on the tert-butyl group was synthesized. Cyclic voltammetry (CV) was used to investigate their electrochemical properties and showed a more pronounced substituent effect for oxidation than for reduction. Rate constants of superoxide radical (O2•–) reactions with nitrones were determined using a UV–vis stopped-flow method, and phenyl radical (Ph•) trapping rate constants were measured by EPR spectroscopy. The effect of N-tert-butyl substitution on the charge density and electron density localization of the nitronyl carbon as well as on the free energies of nitrone reactivity with O2•– and HO2• were computationally rationalized at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level of theory. Theoretical and experimental data showed that the rates of the reaction correlate with the nitronyl carbon charge density, suggesting a nucleophilic nature of O2•– and Ph• addition to the nitronyl carbon atom. Finally, the substituent effect was investigated in cell cultures exposed to hydrogen peroxide and a correlation between the cell viability and the oxidation potential of the nitrones was observed. Through a combination of computational methodologies and experimental methods, new insights into the reactivity of free radicals with nitrone derivatives have been proposed. PMID:24968285

Resistance of Salmonella typhimurium TA 1535 to O6-guanine methylation and mutagenesis induced by low doses of N-methyl-N'-nitro-N-nitrosoguanidine: an apparent constitutive repair activity.

PubMed

Guttenplan, J B; Milstein, S

1982-01-01

Salmonella tester strains which are reverted by base-pair substitution mutagens are relatively insensitive to the mutagenic effects of N-methyl-N-nitroso compounds. One reason for this insensitivity is the ability of these strains to withstand low doses of these compounds before they become sensitive to their mutagenic effects. In this report it is shown that mutagenesis induced by treatment of Salmonella typhimurium TA 1535 with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) in buffer is biphasic with a low sensitivity range at low doses where little mutagenesis occurs, followed by a high sensitivity range whose onset begins after an apparent threshold dose has been exceeded. levels of O6-methylguanine (O6-MeG) in the DNA extracted from the bacteria follow a similar dose-response curve suggesting a dependency of mutagenesis on O6-MeG. In contrast, levels of 7-methylguanine (7-MeG) in the DNA increase linearly with dose. O6-MeG was undetectable at the lowest dose of MNNG whereas 7-MeG was readily detectable. Although such resistance to O6-alkylation has been demonstrated in MNNG- pretreated (adapted) E. coli, it has not been reported in unpretreated cells. Then isolated DNA was treated with MNNG a linear dose-response in the generation of O6-MeG was observed. The lack of O6-MeG in DNA isolated from MNNG treated cells after low doses is attributed to a saturable, constitutive repair activity in the bacteria. An attempt to observe the removal of O6-MeG from the bacteria after exposure to a short challenge dose of N-nitroso-N-methylurea (NMU) followed by a subsequent incubation in buffer was unsuccessful, probably because all the repair occurred within the time necessary to treat and lyse the cells.

Determination of acrylamide and methacrylamide by normal phase high performance liquid chromatography and UV detection.

PubMed

Paleologos, E K; Kontominas, M G

2005-06-10

A method using normal phase high performance liquid chromatography (NP-HPLC) with UV detection was developed for the analysis of acrylamide and methacrylamide. The method relies on the chromatographic separation of these analytes on a polar HPLC column designed for the separation of organic acids. Identification of acrylamide and methacrylamide is approached dually, that is directly in their protonated forms and as their hydrolysis products acrylic and methacrylic acid respectively, for confirmation. Detection and quantification is performed at 200 nm. The method is simple allowing for clear resolution of the target peaks from any interfering substances. Detection limits of 10 microg L(-1) were obtained for both analytes with the inter- and intra-day RSD for standard analysis lying below 1.0%. Use of acetonitrile in the elution solvent lowers detection limits and retention times, without impairing resolution of peaks. The method was applied for the determination of acrylamide and methacrylamide in spiked food samples without native acrylamide yielding recoveries between 95 and 103%. Finally, commercial samples of french and roasted fries, cookies, cocoa and coffee were analyzed to assess applicability of the method towards acrylamide, giving results similar with those reported in the literature.

Reducing Mg Acceptor Activation-Energy in Al0.83Ga0.17N Disorder Alloy Substituted by Nanoscale (AlN)5/(GaN)1 Superlattice Using MgGa δ-Doping: Mg Local-Structure Effect

NASA Astrophysics Data System (ADS)

Zhong, Hong-Xia; Shi, Jun-Jie; Zhang, Min; Jiang, Xin-He; Huang, Pu; Ding, Yi-Min

2014-10-01

Improving p-type doping efficiency in Al-rich AlGaN alloys is a worldwide problem for the realization of AlGaN-based deep ultraviolet optoelectronic devices. In order to solve this problem, we calculate Mg acceptor activation energy and investigate its relationship with Mg local structure in nanoscale (AlN)5/(GaN)1 superlattice (SL), a substitution for Al0.83Ga0.17N disorder alloy, using first-principles calculations. A universal picture to reduce acceptor activation energy in wide-gap semiconductors is given for the first time. By reducing the volume of the acceptor local structure slightly, its activation energy can be decreased remarkably. Our results show that Mg acceptor activation energy can be reduced significantly from 0.44 eV in Al0.83Ga0.17N disorder alloy to 0.26 eV, very close to the Mg acceptor activation energy in GaN, and a high hole concentration in the order of 1019 cm-3 can be obtained in (AlN)5/(GaN)1 SL by MgGa δ-doping owing to GaN-monolayer modulation. We thus open up a new way to reduce Mg acceptor activation energy and increase hole concentration in Al-rich AlGaN.

Reducing Mg Acceptor Activation-Energy in Al0.83Ga0.17N Disorder Alloy Substituted by Nanoscale (AlN)5/(GaN)1 Superlattice Using MgGa δ-Doping: Mg Local-Structure Effect

PubMed Central

Zhong, Hong-xia; Shi, Jun-jie; Zhang, Min; Jiang, Xin-he; Huang, Pu; Ding, Yi-min

2014-01-01

Improving p-type doping efficiency in Al-rich AlGaN alloys is a worldwide problem for the realization of AlGaN-based deep ultraviolet optoelectronic devices. In order to solve this problem, we calculate Mg acceptor activation energy and investigate its relationship with Mg local structure in nanoscale (AlN)5/(GaN)1 superlattice (SL), a substitution for Al0.83Ga0.17N disorder alloy, using first-principles calculations. A universal picture to reduce acceptor activation energy in wide-gap semiconductors is given for the first time. By reducing the volume of the acceptor local structure slightly, its activation energy can be decreased remarkably. Our results show that Mg acceptor activation energy can be reduced significantly from 0.44 eV in Al0.83Ga0.17N disorder alloy to 0.26 eV, very close to the Mg acceptor activation energy in GaN, and a high hole concentration in the order of 1019 cm−3 can be obtained in (AlN)5/(GaN)1 SL by MgGa δ-doping owing to GaN-monolayer modulation. We thus open up a new way to reduce Mg acceptor activation energy and increase hole concentration in Al-rich AlGaN. PMID:25338639

Reducing Mg acceptor activation-energy in Al(0.83)Ga(0.17)N disorder alloy substituted by nanoscale (AlN)₅/(GaN)₁ superlattice using Mg(Ga) δ-doping: Mg local-structure effect.

PubMed

Zhong, Hong-xia; Shi, Jun-jie; Zhang, Min; Jiang, Xin-he; Huang, Pu; Ding, Yi-min

2014-10-23

Improving p-type doping efficiency in Al-rich AlGaN alloys is a worldwide problem for the realization of AlGaN-based deep ultraviolet optoelectronic devices. In order to solve this problem, we calculate Mg acceptor activation energy and investigate its relationship with Mg local structure in nanoscale (AlN)5/(GaN)1 superlattice (SL), a substitution for Al(0.83)Ga(0.17)N disorder alloy, using first-principles calculations. A universal picture to reduce acceptor activation energy in wide-gap semiconductors is given for the first time. By reducing the volume of the acceptor local structure slightly, its activation energy can be decreased remarkably. Our results show that Mg acceptor activation energy can be reduced significantly from 0.44 eV in Al(0.83)Ga(0.17)N disorder alloy to 0.26 eV, very close to the Mg acceptor activation energy in GaN, and a high hole concentration in the order of 10(19) cm(-3) can be obtained in (AlN)5/(GaN)1 SL by Mg(Ga) δ-doping owing to GaN-monolayer modulation. We thus open up a new way to reduce Mg acceptor activation energy and increase hole concentration in Al-rich AlGaN.

CO 2 Reduction Selective for C ≥2 Products on Polycrystalline Copper with N-Substituted Pyridinium Additives

DOE PAGES

Han, Zhiji; Kortlever, Ruud; Chen, Hsiang -Yun; ...

2017-07-21

Electrocatalytic CO 2 reduction to generate multicarbon products is of interest for applications in artificial photosynthetic schemes. This is a particularly attractive goal for CO 2 reduction by copper electrodes, where a broad range of hydrocarbon products can be generated but where selectivity for C–C coupled products relative to CH 4 and H 2 remains an impediment. Herein we report a simple yet highly selective catalytic system for CO 2 reduction to C ≥2 hydrocarbons on a polycrystalline Cu electrode in bicarbonate aqueous solution that uses N-substituted pyridinium additives. Selectivities of 70–80% for C 2 and C 3 products withmore » a hydrocarbon ratio of C ≥2/CH 4 significantly greater than 100 have been observed with several additives. 13C-labeling studies verify CO 2 to be the sole carbon source in the C ≥2 hydrocarbons produced. Upon electroreduction, the N-substituted pyridinium additives lead to film deposition on the Cu electrode, identified in one case as the reductive coupling product of N-arylpyridinium. As a result, product selectivity can also be tuned from C ≥2 species to H 2 (~90%) while suppressing methane with certain N-heterocyclic additives.« less

CO 2 Reduction Selective for C ≥2 Products on Polycrystalline Copper with N-Substituted Pyridinium Additives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Zhiji; Kortlever, Ruud; Chen, Hsiang -Yun

Electrocatalytic CO 2 reduction to generate multicarbon products is of interest for applications in artificial photosynthetic schemes. This is a particularly attractive goal for CO 2 reduction by copper electrodes, where a broad range of hydrocarbon products can be generated but where selectivity for C–C coupled products relative to CH 4 and H 2 remains an impediment. Herein we report a simple yet highly selective catalytic system for CO 2 reduction to C ≥2 hydrocarbons on a polycrystalline Cu electrode in bicarbonate aqueous solution that uses N-substituted pyridinium additives. Selectivities of 70–80% for C 2 and C 3 products withmore » a hydrocarbon ratio of C ≥2/CH 4 significantly greater than 100 have been observed with several additives. 13C-labeling studies verify CO 2 to be the sole carbon source in the C ≥2 hydrocarbons produced. Upon electroreduction, the N-substituted pyridinium additives lead to film deposition on the Cu electrode, identified in one case as the reductive coupling product of N-arylpyridinium. As a result, product selectivity can also be tuned from C ≥2 species to H 2 (~90%) while suppressing methane with certain N-heterocyclic additives.« less

Microsynthesis and electron ionization mass spectral studies of O(S)-alkyl N,N-dimethyl alkylphosphono(thiolo)thionoamidates for Chemical Weapons Convention verification.

PubMed

Saeidian, Hamdollah; Babri, Mehran; Abdoli, Morteza; Sarabadani, Mansour; Ashrafi, Davood; Naseri, Mohammad Taghi

2012-12-15

The availability of mass spectra and interpretation skills are essential for unambiguous identification of the Chemical Weapons Convention (CWC)-related chemicals. The O(S)-alkyl N,N-dimethyl alkylphosphono(thiolo)thionoamidates are included in the list of scheduled CWC-related compounds, but there are very few spectra from these compounds in the literature. This paper examines these spectra and their mass spectral fragmentation routes. The title chemicals were prepared through microsynthetic protocols and were analyzed using electron ionization mass spectrometry with gas chromatography as a MS-inlet system. Structures of fragments were confirmed using analysis of fragment ions of deuterated analogs, tandem mass spectrometry and density functional theory (DFT) calculations. Mass spectrometric studies revealed some interesting fragmentation pathways during the ionization process, such as alkene and amine elimination and McLafferty-type rearrangements. The most important fragmentation route of the chemicals is the thiono-thiolo rearrangement. DFT calculations are used to support MS results and to reveal relative preference formation of fragment ions. The retention indices (RIs) of all the studied compounds are also reported. Mass spectra of the synthesized compounds were investigated with the aim to enrich the Organization for the Prohibition of Chemical Weapons (OPCW) Central Analytical Database (OCAD) which may be used for detection and identification of CWC-related chemicals during on-site inspection and/or off-site analysis such as OPCW proficiency tests. Copyright © 2012 John Wiley & Sons, Ltd.

Probing the N-5 region of the indoloquinoline alkaloid, cryptolepine for anticryptococcal activity.

PubMed

Ablordeppey, S Y; Fan, P; Clark, A M; Nimrod, A

1999-02-01

N-5 Alkylated analogues of cryptolepine were synthesized and tested for anticryptococcal activity. Evidence provided in this study suggests that the active form of cryptolepine consists of the flat tetracyclic aromatic ring with the methyl group on the N-5 atom. It was also found that changes in the electronic density around the N-5 atom do not appear to affect activity. Steric hindrance of the N-5 substituents seems to decrease activity. Through systematic modification of the N-5 alkyl groups, o-phenylpentyl group was shown to possess the highest potency thus far.

Effect of alkyl chain length on the rotational diffusion of nonpolar and ionic solutes in 1-alkyl-3-methylimidazolium-bis(trifluoromethylsulfonyl)imides.

PubMed

Gangamallaiah, V; Dutt, G B

2013-10-10

Rotational diffusion of a nonpolar solute 9-phenylanthracene (9-PA) and a cationic solute rhodamine 110 (R110) has been examined in a series of 1-alkyl-3-methylimidazolium (alkyl = octyl, decyl, dodecyl, tetradecyl, hexadecyl, and octadecyl) bis(trifluoromethylsulfonyl)imides to understand the influence of alkyl chain length on solute rotation. In this study, reorientation times (τr) have been measured as a function of viscosity (η) by varying the temperature (T) of the solvents. These results have been analyzed using the Stokes-Einstein-Debye (SED) hydrodynamic theory along with the ones obtained for the same solutes in 1-alkyl-3-methylimidazolium (alkyl = methyl, ethyl, propyl, butyl, and hexyl) bis(trifluoromethylsulfonyl)imides (Gangamallaiah and Dutt, J. Phys. Chem. B 2012, 116, 12819-12825). It has been noticed that the data for 9-PA and R110 follows the relation τr = A(η/T)(n) with A being the ratio of hydrodynamic volume of the solute to the Boltzmann constant and n = 1 as envisaged by the SED theory. However, upon increasing the alkyl chain length from methyl to octadecyl significant deviations from the SED theory have been observed especially from the octyl derivative onward. From methyl to octadecyl derivatives, the value of A decreases by a factor of 3 for both the solutes and n by a factor of 1.4 and 1.6 for 9-PA and R110, respectively. These observations have been rationalized by taking into consideration the organized structure of the ionic liquids, whose influence appears to be pronounced when the number of carbon atoms in the alkyl chain attached to the imidazolium cation exceeds eight.

Synthesis, Biological Evaluation, and Autophagy Mechanism of 12N-Substituted Sophoridinamines as Novel Anticancer Agents.

PubMed

Bi, Chongwen; Zhang, Na; Yang, Peng; Ye, Cheng; Wang, Yanxiang; Fan, Tianyun; Shao, Rongguang; Deng, Hongbin; Song, Danqing

2017-02-09

A series of 12 N -substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N '-end could greatly enhance antiproliferation potency. Among them, compound 6b possessing a N '-trimethoxyphenyl methylene exhibited potent antiproliferation effect against three human tumor cell lines including HepG2, leukemia (K562), and breast cancer (HMLE), with IC 50 between 0.55 and 1.7 μM. The underlying mechanism of 6b against tumor cells is to block autophagic flux, mainly through neutralizing lysosomal acidity. Our results indicated that compound 6b is a potent lysosomal deacidification agent and is accordingly able to block autophagic flux and inhibit tumor cell growth.

A quantum chemistry study on surface reactivity of pristine and carbon-substituted AlN nanotubes

NASA Astrophysics Data System (ADS)

Mahdaviani, Amir; Esrafili, Mehdi D.; Esrafili, Ali; Behzadi, Hadi

2013-09-01

A density functional theory investigation was performed to predict the surface reactivity of pristine and carbon-substituted (6,0) single-walled aluminum nitride nanotubes (AlNNTs). The properties determined include the electrostatic potentials VS(r) and average local ionization energies ĪS(r) on the surfaces of the investigated tubes. According to computed VS(r) results, the Al/N atoms in edge or cap regions show a different reactivity pattern than those at the middle portion of the tubes. Due to the carbon-substitution at the either Al or N sites of the tubes, the negative regions associated with nitrogen atoms are stronger than before. The prediction of surface reactivity and regioselectivity using average local ionization energies has been verified by atomic hydrogen chemisorption energies calculated for AlNNTs at the B3LYP/6-31 G* level. There is an acceptable correlation between the minima of ĪS(r) and the atomic hydrogen chemisorption energies, demonstrating that ĪS(r) provides an effective means for rapidly and economically assessing the relative reactivities of finite sized AlNNTs.

Synthesis and anticancer activity of N-substituted 2-arylquinazolinones bearing trans-stilbene scaffold.

PubMed

Mahdavi, Mohammad; Pedrood, Keyvan; Safavi, Maliheh; Saeedi, Mina; Pordeli, Mahboobeh; Ardestani, Sussan Kabudanian; Emami, Saeed; Adib, Mehdi; Foroumadi, Alireza; Shafiee, Abbas

2015-05-05

A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were designed, synthesized, and evaluated against human breast cancer cell lines including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl derivative 7h showed the best profile of activity (IC50 < 5 μM) against all cell lines, being 2-fold more potent than standard drug, etoposide. Our investigation revealed that the cytotoxic activity was significantly affected by N3-alkyl substituents. Furthermore, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that the prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Substitution and Redox Chemistry of [Bu(4)N](2)[Ta(6)Cl(12)(OSO(2)CF(3))(6)].

PubMed

Prokopuk, Nicholas; Kennedy, Vance O.; Stern, Charlotte L.; Shriver, Duward F.

1998-09-21

Two sequential electrochemical reductions occur for the cluster anion [Ta(6)Cl(12)(OSO(2)CF(3))(6)](2)(-) at 0.89 and 0.29 V vs Ag/AgCl, with the generation [Ta(6)Cl(12)(OSO(2)CF(3))(6)](3)(-) and [Ta(6)Cl(12)(OSO(2)CF(3))(6)](4)(-). Chemical reduction of [Ta(6)Cl(12)(OSO(2)CF(3))(6)](2)(-) by ferrocene produces [Ta(6)Cl(12)(OSO(2)CF(3))(6)](3)(-) with the concomitant shift of the nu(SO(2)) stretch from 1002 to 1018 cm(-)(1). Reaction of [Bu(4)N](2)[Ta(6)Cl(12)(OSO(2)CF(3))(6)] (1) with [Bu(4)N]X (X = Cl, Br, I, NCS) occurs by reduction and substitution, yielding [Bu(4)N](3)[Ta(6)Cl(12)X(6)], where the clusters with X = Br, I, and NCS are new. Spectroscopic (IR and UV-vis) evidence indicates that the reduced cluster core {Ta(6)Cl(12)}(2+) is produced in reaction mixtures of 1 with the halide and pseudohalide ions. Concomitant substitution of the triflate ligands of 1 by X(-) occurs and the rates for the overall reduction and substitution increase in the order X(-) = Cl(-) < Br(-) < NCS(-) < I(-) < CN(-). Reduction of 1 with ferrocene followed by addition of [Bu(4)N]O(2)CCH(3) produces the new cluster [Ta(6)Cl(12)(O(2)CCH(3))(6)](3)(-) isolated as the tetrabutylammonium salt. Cyclic voltammetry and UV-vis spectroscopy on the new clusters [Bu(4)N](3)[Ta(6)Cl(12)X(6)] (X = Br, I, NCS, and O(2)CCH(3)) are reported. Crystal data for [Bu(4)N](3)[Ta(6)Cl(12)(NCS)(6)].CH(2)Cl(2): monoclinic, space group, P2(1)/c (No. 14); a = 25.855(6) Å, b = 21.843(6) Å, c = 16.423(3) Å; beta = 100.03(2) degrees; V = 9133(3) Å(3); Z = 4.

In vitro induction of micronuclei by monofunctional methanesulphonic acid esters: possible role of alkylation mechanisms.

PubMed

Eder, Erwin; Kütt, Wolfgang; Deininger, Christoph

2006-12-01

Six monofunctional alkylating methanesulphonates of widely varying structures were investigated in the in vitro micronucleus assay with Syrian hamster embryo fibroblast cells. The results were compared with the alkylating activities measured in the 4-(nitrobenzyl)pyridine test (NBP-test) and the N-methyl mercaptoimidazole (MMI-test) as measures for S(N)2 reactivity as well as in the triflouoroacetic acid (TFA) solvolysis and the hydrolysis reaction as measures for S(N)1 reactivity in order to provide insights into the role of alkylation mechanisms on induction of micronuclei. Moreover we compared the results of micronucleus assay with those of the Ames tests in strain TA 100 and TA1535 and with those of the SOS chromotest with the strains PQ37, PQ243, PM21 and GC 4798. The potency of methanesulphonates to induce micronuclei depended only to a certain degree, on the total alkylating activity (S(N)1 and S(N)2 reactivity). An inverse, significant correlation between the Ames test and the micronucleus assay was observed and an inverse correlation between the micronucleus assay and the SOS chromotest with the different strains. The results indicate that the primary mechanism leading to induction of micronuclei is not O-alkylation in DNA as it is the case in the Ames test with the hisG46 strains TA1535 and TA100 and not N-alkylation as with the SOS chromotest. There is evidence that protein alkylation, e.g. in the spindle apparatus in mitosis is decisive for induction of micronuclei by alkylating compounds. The structurally voluminous methanesulphonates 2-phenyl ethyl methanesulphonate and 1-phenyl-2-propyl methanesulphonate show a clear higher micronuclei inducing potency than the other tested though the bulky methanesulphonates possess a lower total alkylating activity than the others. This effect can be explained by a higher disturbance during mitosis after alkylation of the spindle apparatus with the structurally more bulky methanesulphonates.

Electrochemical fluorination of trichloroethylene and N, N-dimethyltrifluoroacetamide

NASA Technical Reports Server (NTRS)

Hsu, L. C.

1979-01-01

Fluorination of trichloroethylene and N, N-dimethyltrifluoroacetamide was carried out on a laboratory scale in an advanced Simons type electrochemical apparatus which could be operated automatically from ambient to 50 psi pressure. A variety of fluorine-substituted products are formed, depending upon electrolysis conditions and concentrations of reactant relative to the NaF, KF, HF electrolyte. A new reaction mechanism of electrochemical fluorination of trichloroethylene is proposed. The solvency-to-fluorine content relationship of fluorinated N, N-dimethyltrifluoroacetamide is described.

Complete regioselective addition of grignard reagents to pyrazine N-oxides, toward an efficient enantioselective synthesis of substituted piperazines.

PubMed

Andersson, Hans; Banchelin, Thomas Sainte-Luce; Das, Sajal; Gustafsson, Magnus; Olsson, Roger; Almqvist, Fredrik

2010-01-15

A conceptually new one-pot strategy for the synthesis of protected substituted piperazines via the addition of Grignard reagents to pyrazine N-oxides is presented. This strategy is high yielding (33-91% over three steps), step-efficient, and fast. The synthesized N,N-diprotected piperazines are convenient to handle and allow for orthogonal deprotection at either nitrogen for selective transformations. In addition, this is a synthetic route to enantiomerically enriched piperazines by using a combination of phenyl magnesium chloride and (-)-sparteine, which resulted in enantiomeric excesses up to 83%.

Anaerobic biotransformation of roxarsone and related N-substituted phenylarsonic acids

USGS Publications Warehouse

Cortinas, I.; Field, J.A.; Kopplin, M.; Garbarino, J.R.; Gandolfi, A.J.; Sierra-Alvarez, R.

2006-01-01

Large quantities of arsenic are introduced into the environment through land application of poultry litter containing the organoarsenical feed additive roxarsone (3-nitro-4-hydroxyphenylarsonic acid). The objective of this study was to evaluate the bioconversion of roxarsone and related N-substituted phenylarsonic acid derivatives under anaerobic conditions. The results demonstrate that roxarsone is rapidly transformed in the absence of oxygen to the corresponding aromatic amine, 4-hydroxy-3-aminophenylarsonic acid (HAPA). The formation of HAPA is attributable to the facile reduction of the nitro group. Electron-donating substrates, such as hydrogen gas, glucose, and lactate, stimulated the rate of nitro group reduction, indicating a microbial role. During long-term incubations, HAPA and the closely related 4-aminophenylarsonic acid (4-APA) were slowly biologically eliminated by up to 99% under methanogenic and sulfate-reducing conditions, whereas little or no removal occurred in heat-killed inoculum controls. Arsenite and, to a lesser extent, arsenate were observed as products of the degradation. Freely soluble forms of the inorganic arsenical species accounted for 19-28% of the amino-substituted phenylarsonic acids removed. This constitutes the first report of a biologically catalyzed rupture of the phenylarsonic group under anaerobic conditions. ?? 2006 American Chemical Society.

Effects of alkyl chain length and substituent pattern of fullerene bis-adducts on film structures and photovoltaic properties of bulk heterojunction solar cells.

PubMed

Tao, Ran; Umeyama, Tomokazu; Kurotobi, Kei; Imahori, Hiroshi

2014-10-08

A series of alkoxycarbonyl-substituted dihydronaphthyl-based [60]fullerene bis-adduct derivatives (denoted as C2BA, C4BA, and C6BA with the alkyl chain of ethyl, n-butyl, and n-hexyl, respectively) have been synthesized to investigate the effects of alkyl chain length and substituent pattern of fullerene bis-adducts on the film structures and photovoltaic properties of bulk heterojunction polymer solar cells. The shorter alkyl chain length caused lower solubility of the fullerene bis-adducts (C6BA > C4BA > C2BA), thereby resulting in the increased separation difficulty of respective bis-adduct isomers. The device performance based on poly(3-hexylthiophene) (P3HT) and the fullerene bis-adduct regioisomer mixtures was enhanced by shortening the alkyl chain length. When using the regioisomerically separated fullerene bis-adducts, the devices based on trans-2 and a mixture of trans-4 and e of C4BA exhibited the highest power conversion efficiencies of ca. 2.4%, which are considerably higher than those of the C6BA counterparts (ca. 1.4%) and the C4BA regioisomer mixture (1.10%). The film morphologies as well as electron mobilities of the P3HT:bis-adduct blend films were found to affect the photovoltaic properties considerably. These results reveal that the alkyl chain length and substituent pattern of fullerene bis-adducts significantly influence the photovoltaic properties as well as the film structures of bulk heterojunction solar cells.

Copper-catalyzed intermolecular and regioselective aminofluorination of styrenes: facile access to β-fluoro-N-protected phenethylamines.

PubMed

Saavedra-Olavarría, Jorge; Arteaga, Gean C; López, Jhon J; Pérez, Edwin G

2015-02-25

A copper-catalyzed regio- and intermolecular aminofluorination of styrenes has been developed. In this reaction Ph-I=N-Ts and Et3N·3HF act as nitrogen and fluorine sources, respectively. The obtained β-fluoro-N-Ts-phenethylamines can be N-alkylated with subsequent deprotection affording the corresponding β-fluoro-N-alkylated phenethylamines, which are interesting building blocks for compounds acting on neuronal targets.

Substitution of D701N in the PB2 protein could enhance the viral replication and pathogenicity of Eurasian avian-like H1N1 swine influenza viruses.

PubMed

Liu, Suli; Zhu, Wenfei; Feng, Zhaomin; Gao, Rongbao; Guo, Junfeng; Li, Xiyan; Liu, Jia; Wang, Dayan; Shu, Yuelong

2018-05-02

Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs) have become predominant in pig populations in China and have recently been reported to have the most potential to raise the next pandemic in humans. The mutation D701N in the PB2 protein, which accounts for 31% of H1N1 SIVs, has previously been shown to contribute to the adaptation of the highly pathogenic H5N1 or H7N7 avian influenza viruses in mammals. However, little is known of the effects of this substitution on the EA H1N1 viruses. Herein, we investigated the contributions of 701N in the PB2 protein to an EA H1N1 SIV (A/Hunan/42443/2015(H1N1), HuN EA-H1N1), which had 701D in the PB2 protein. Our results found that viral polymerase activity, viral replication, and pathogenicity in mice were indeed enhanced due to the introduction of 701N into the PB2 protein, and the increased viral growth was partly mediated by the host factor importin-α7. Thus, substantial attention should be paid to the D701N mutation in pig populations.

Synthesis and stereochemical analysis of β-nitromethane substituted γ-amino acids and peptides.

PubMed

Ganesh Kumar, Mothukuri; Mali, Sachitanand M; Gopi, Hosahudya N

2013-02-07

The high diastereoselectivity in the Michael addition of nitromethane to α,β-unsaturated γ-amino esters, crystal conformations of β-nitromethane substituted γ-amino acids and peptides are studied. Results suggest that the N-Boc protected amide NH, conformations of α,β-unsaturated γ-amino esters and alkyl side chains play a crucial role in dictating the high diastereoselectivity of nitromethane addition to E-vinylogous amino esters. Investigation of the crystal conformations of both α,β-unsaturated γ-amino esters and the Michael addition products suggests that an H-C(γ)-C(β)=C(α) eclipsed conformer of the unsaturated amino ester leads to the major (anti) product compared to that of an N-C(γ)-C(β)=C(α) eclipsed conformer. The major diastereomers were separated and subjected to the peptide synthesis. The single crystal analysis of the dipeptide containing β-nitromethane substituted γ-amino acids reveals a helical type of folded conformation with an isolated H-bond involving a nine-atom pseudocycle.

Sorbate-nitrite interactions: acetonitrile oxide as an alkylating agent.

PubMed

Pérez-Prior, M Teresa; Gómez-Bombarelli, Rafael; González-Pérez, Marina; Manso, José A; García-Santos, M Pilar; Calle, Emilio; Casado, Julio

2009-07-01

Because chemical species with DNA-damaging and mutagenic activity are formed in sorbate-nitrite mixtures and because sorbic acid sometimes coexists with nitrite occurring naturally or incorporated as a food additive, the study of sorbate-nitrite interactions is important. Here, the alkylating potential of the products resulting from such interactions was investigated. Drawn were the following conclusions: (i) Acetonitrile oxide (ACNO) is the compound responsible for the alkylating capacity of sorbate-nitrite mixtures; (ii) ACNO alkylates 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, forming an adduct (AD; epsilon = 1.4 x 10(4) M(-1) cm(-1); lambda = 519 nm); (iii) the NBP alkylation reaction complies with the rate equation, r = d[AD]/dt = k(alk)(ACNO)[ACNO][NBP]-k(hyd)(AD)[AD], k(alk)(ACNO) being the NBP alkylation rate constant for ACNO and k(hyd)(AD) the rate constant for the adduct hydrolysis reaction; (iv) the small fraction of ACNO forming the adduct with NBP, as well as the small magnitude of the quotient (k(alk) (ACNO)/k(hyd)(ACNO)) as compared with those reported for other alkylating agents, such as some lactones and N-alkyl-N-nitrosoureas, reveals the ACNO effective alkylating capacity to be less significant; (v) the low value of the NBP-ACNO adduct life (defined as the total amount of adduct present along the progression of the NBP alkylation per unit of alkylating agent concentration) points to the high instability of this adduct; and (vi) the obtained results are in accordance with the low carcinogenicity of ACNO.

The implications of water extractable organic matter (WEOM) on the sorption of typical parent, alkyl and N/O/S-containing polycyclic aromatic hydrocarbons (PAHs) by microplastics.

PubMed

Li, Ruilong; Tan, Huadong; Zhang, Linlin; Wang, Shaopeng; Wang, Yinghui; Yu, Kefu

2018-07-30

Microplastics sorption of persistent organic pollutants (POPs) was the core processes that cause negative effects to biota, and their influencing factors and related mechanisms are poorly understood. In this study, we explored the impacts of water extractable organic matter (WEOM), an important source of endogenous dissolved organic matter in mangrove sediment, on the sorption coefficients of typical parent, alkyl and N/O/S-containing polycyclic aromatic hydrocarbons (PAHs) by microplastics. The presence of L-WEOM (D) impeded the PAHs sorption as the coefficients (K f ) decreased to 10.17 (μg/kg)/(μg/L) n and to 8.39 (μg/kg)/(μg/L) n for fluorene (Flu) and 1-methyl-fluorene (1-M-Flu), respectively. The K f exhibited good linear relationships with the aliphaticity of L-WEOM (p < 0.05) rather than the aromatic carbon/alkyl carbon content (p > 0.05). Under the presences of L-WEOM (D), (S) and (K), the lone pair electrons of N/O/S-containing PAHs was the dominant factor contributing to the obvious difference of the K f values from the other groups. Moreover, the largest impact of L-WEOM (D) on the Flu sorption was in the case of PVC microplastics, while almost no effect was in the case of PS microplastics. The findings of our work may be helpful in improving our understanding of the role of WEOM on the sorption of PAHs to microplastics in the field mangrove sediment. Copyright © 2018 Elsevier Inc. All rights reserved.

Electrochemical fluorination of trichloroethylene and N, N-dimethyltrifluoroacetamide

NASA Technical Reports Server (NTRS)

Hsu, L.-C.

1979-01-01

The paper presents the results of experiments concerning the fluorination of trichloroethylene and N, N-dimethyltrifluoroacetamide carried out on a laboratory scale in an advanced 'Simons' type electrochemical apparatus which could be operated automatically from ambient to 50 psi pressure. It is shown that a variety of fluorine-substituted products are formed, depending upon electrolysis conditions and concentrations of reactant relative to the NaF, KF, HF electrolyte. A new reaction mechanism of electrochemical fluorination of trichloroethylene is proposed. Finally, the solvency-to-fluorine content relationship of fluorinated N, N-dimethyltrifluoroacetamide is described.

Vapor pressures of 1,3-dialkylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquids with long alkyl chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocha, Marisa A. A., E-mail: lbsantos@fc.up.pt, E-mail: marisa.alexandra.rocha@gmail.com; Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven; Coutinho, João A. P.

2014-10-07

This work presents the vapor pressure at several temperatures for the 1,3-dialkylimidazolium bis(trifluoromethylsulfonyl)imide series, [C{sub N/2}C{sub N/2}im][NTf{sub 2}] (N = 14, 16, 18, and 20), measured by a Knudsen effusion method combined with a quartz crystal microbalance. The thermodynamic properties of vaporization of the ionic liquids under study are analysed together with the results obtained previously for the shorter alkyl chain length [C{sub N/2}C{sub N/2}im][NTf{sub 2}] (N = 2, 4, 6, 8, 10, and 12), in order to evaluate the effect of the alkyl side chains of the cation and to get additional insights concerning the nanostructuration of ionic liquids.more » The symmetry effect is explored, based on the comparison with the asymmetric imidazolium based ionic liquids, [C{sub N-1}C{sub 1}im][NTf{sub 2}]. A trend shift on the thermodynamic properties of vaporization along the alkyl side chains of the extended symmetric ionic liquids, around [C{sub 6}C{sub 6}im][NTf{sub 2}], was detected. An intensification of the odd-even effect was observed starting from [C{sub 6}C{sub 6}im][NTf{sub 2}], with higher enthalpies and entropies of vaporization for the odd numbered ionic liquids, [C{sub 7}C{sub 7}im][NTf{sub 2}] and [C{sub 9}C{sub 9}im][NTf{sub 2}]. Similar, but less pronounced, odd-even effect was found for the symmetric ionic liquids with lower alkyl side chains length, [C{sub N/2}C{sub N/2}im][NTf{sub 2}] (with N = 4, 6, 8, 10, and 12). This effect is related with the predominant orientation of the terminal methyl group of the alkyl chain to the imidazolium ring and their influence in the cation-anion interaction. The same Critical Alkyl length at the hexyl, (C{sub 6}C{sub 1}and C{sub 6}C{sub 6}) was found for both asymmetric and symmetric series indicating that the nanostructuration of the ionic liquids is related with alkyl chain length.« less

Asymmetric allylation of α-ketoester-derived N-benzoylhydrazones promoted by chiral sulfoxides/N-oxides Lewis bases: highly enantioselective synthesis of quaternary α-substituted α-allyl-α-amino acids.

PubMed

Reyes-Rangel, Gloria; Bandala, Yamir; García-Flores, Fred; Juaristi, Eusebio

2013-09-01

Chiral sulfoxides/N-oxides (R)-1 and (R,R)-2 are effective chiral promoters in the enantioselective allylation of α-keto ester N-benzoylhydrazone derivatives 3a-g to generate the corresponding N-benzoylhydrazine derivatives 4a-g, with enantiomeric excesses as high as 98%. Representative hydrazine derivatives 4a-b were subsequently treated with SmI2, and the resulting amino esters 5a-b with LiOH to obtain quaternary α-substituted α-allyl α-amino acids 6a-b, whose absolute configuration was assigned as (S), with fundament on chemical correlation and electronic circular dichroism (ECD) data. © 2013 Wiley Periodicals, Inc.

Tuning of superconductivity by Ni substitution into noncentrosymmetric ThC o1 -xN ixC2

NASA Astrophysics Data System (ADS)

Grant, T. W.; Cigarroa, O. V.; Rosa, P. F. S.; Machado, A. J. S.; Fisk, Z.

2017-07-01

The recently discovered noncentrosymmetric superconductor ThCoC2 was observed to show unusual superconducting behavior with a critical temperature of Tc=2.65 K . Here we investigate the effect of nickel substitution on the superconducting state in ThC o1 -xN ixC2 . Magnetization, resistivity, and heat capacity measurements demonstrate Ni substitution has a dramatic effect with critical temperature increased up to Tc=12.1 K for x =0.4 Ni concentration, which is a rather high transition temperature for a noncentrosymmetric superconductor. In addition, the unusual superconducting characteristics observed in pure ThCoC2 appear to be suppressed or tuned with Ni substitution towards a more conventional fully gapped superconductor.

σ Receptor Effects of N-Substituted Benztropine Analogs: Implications for Antagonism of Cocaine Self-Administration

PubMed Central

Hiranita, Takato; Hong, Weimin C.; Kopajtic, Theresa

2017-01-01

Several N-substituted benztropine (BZT) analogs are atypical dopamine transport inhibitors as they have affinity for the dopamine transporter (DAT) but have minimal cocaine-like pharmacologic effects and can block numerous effects of cocaine, including its self-administration. Among these compounds, N-methyl (AHN1-055), N-allyl (AHN2-005), and N-butyl (JHW007) analogs of 3α-[bis(4′-fluorophenyl)methoxy]-tropane were more potent in antagonizing self-administration of cocaine and d-methamphetamine than in decreasing food-maintained responding. The antagonism of cocaine self-administration (0.03–1.0 mg/kg per injection) with the above BZT analogs was reproduced in the present study. Further, the stimulant-antagonist effects resembled previously reported effects of pretreatments with combinations of standard DAT inhibitors and σ1-receptor (σ1R) antagonists. Therefore, the present study examined binding of the BZT analogs to σRs, as well as their in vivo σR antagonist effects. Each of the BZT analogs displaced radiolabeled σR ligands with nanomolar affinity. Further, self-administration of the σR agonist DTG (0.1–3.2 mg/kg/injection) was dose dependently blocked by AHN2-005 and JHW007 but potentiated by AHN1-055. In contrast, none of the BZT analogs that were active against DTG self-administration was active against the self-administration of agonists at dopamine D1-like [R(+)-SKF 81297, (±)-SKF 82958 (0.00032–0.01 mg/kg per injection each)], D2-like [R(–)-NPA (0.0001–0.0032 mg/kg per injection), (–)-quinpirole (0.0032–0.1 mg/kg per injection)], or μ-opioid (remifentanil, 0.0001–0.0032 mg/kg per injection) receptors. The present results indicate that behavioral antagonist effects of the N-substituted BZT analogs are specific for abused drugs acting at the DAT and further suggest that σR antagonism contributes to those actions. PMID:28442581

σ Receptor Effects of N-Substituted Benztropine Analogs: Implications for Antagonism of Cocaine Self-Administration.

PubMed

Hiranita, Takato; Hong, Weimin C; Kopajtic, Theresa; Katz, Jonathan L

2017-07-01

Several N-substituted benztropine (BZT) analogs are atypical dopamine transport inhibitors as they have affinity for the dopamine transporter (DAT) but have minimal cocaine-like pharmacologic effects and can block numerous effects of cocaine, including its self-administration. Among these compounds, N -methyl (AHN1-055), N -allyl (AHN2-005), and N -butyl (JHW007) analogs of 3 α -[bis(4'-fluorophenyl)methoxy]-tropane were more potent in antagonizing self-administration of cocaine and d -methamphetamine than in decreasing food-maintained responding. The antagonism of cocaine self-administration (0.03-1.0 mg/kg per injection) with the above BZT analogs was reproduced in the present study. Further, the stimulant-antagonist effects resembled previously reported effects of pretreatments with combinations of standard DAT inhibitors and σ 1 -receptor ( σ 1 R) antagonists. Therefore, the present study examined binding of the BZT analogs to σ Rs, as well as their in vivo σ R antagonist effects. Each of the BZT analogs displaced radiolabeled σ R ligands with nanomolar affinity. Further, self-administration of the σ R agonist DTG (0.1-3.2 mg/kg/injection) was dose dependently blocked by AHN2-005 and JHW007 but potentiated by AHN1-055. In contrast, none of the BZT analogs that were active against DTG self-administration was active against the self-administration of agonists at dopamine D 1 -like [ R (+)-SKF 81297, (±)-SKF 82958 (0.00032-0.01 mg/kg per injection each)], D 2 -like [ R (-)-NPA (0.0001-0.0032 mg/kg per injection), (-)-quinpirole (0.0032-0.1 mg/kg per injection)], or μ -opioid (remifentanil, 0.0001-0.0032 mg/kg per injection) receptors. The present results indicate that behavioral antagonist effects of the N -substituted BZT analogs are specific for abused drugs acting at the DAT and further suggest that σ R antagonism contributes to those actions. U.S. Government work not protected by U.S. copyright.

Hydroperoxide Measurements During Low-Temperature Gas-Phase Oxidation of n-Heptane and n-Decane.

PubMed

Rodriguez, Anne; Herbinet, Olivier; Meng, Xiangzan; Fittschen, Christa; Wang, Zhandong; Xing, Lili; Zhang, Lidong; Battin-Leclerc, Frédérique

2017-03-09

A wide range of hydroperoxides (C 1 -C 3 alkyl hydroperoxides, C 3 -C 7 alkenyl hydroperoxides, C 7 ketohydroperoxides, and hydrogen peroxide (H 2 O 2 )), as well as ketene and diones, have been quantified during the gas-phase oxidation of n-heptane. Some of these species, as well as C 10 alkenyl hydroperoxides and ketohydroperoxides, were also measured during the oxidation of n-decane. These experiments were performed using an atmospheric-pressure jet-stirred reactor at temperatures from 500 to 1100 K and one of three analytical methods, time-of-flight mass spectrometry combined with tunable synchrotron photoionization with a molecular beam sampling: time-of-flight mass spectrometry combined with laser photoionization with a capillary tube sampling, continuous wave cavity ring-down spectroscopy with sonic probe sampling. The experimental temperature at which the maximum mole fraction is observed increases significantly for alkyl hydroperoxides, alkenyl hydroperoxides, and then more so again for hydrogen peroxide, compared to ketohydroperoxides. The influence of the equivalence ratio from 0.25 to 4 on the formation of these peroxides has been studied during n-heptane oxidation. The up-to-date detailed kinetic oxidation models for n-heptane and for n-decane found in the literature have been used to discuss the possible pathways by which these peroxides, ketene, and diones are formed. In general, the model predicts well the reactivity of the two fuels, as well as the formation of major intermediates.

Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary alkyl halides at room temperature.

PubMed

Do, Hien-Quang; Bachman, Shoshana; Bissember, Alex C; Peters, Jonas C; Fu, Gregory C

2014-02-05

The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for SN2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C-N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper-amidate complex, followed by electron transfer to form an alkyl radical.

Chemoselective room temperature E1cB N-N cleavage of oxazolidinone hydrazides from enantioselective aldehyde α-hydrazination: synthesis of (+)-1,4-dideoxyallonojirimycin.

PubMed

Ferreira, Jasmin; Rees-Jones, Sophie C M; Ramaotsoa, Valerie; Msutu, Ath'enkosi; Hunter, Roger

2016-02-07

Room temperature E1cB N-N cleavage of oxazolidinone hydrazides via N-alkylation with diethyl bromomalonate and potassium or caesium carbonate as base in acetonitrile is presented. The new method has a much improved chemoselectivity, which is illustrated by a concise total synthesis of the piperidine iminosugar (+)-1,4-dideoxyallonojirimycin.

Effects of polarizability on the structural and thermodynamics properties of [C{sub n}mim][Gly] ionic liquids (n = 1–4) using EEM/MM molecular dynamic simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Yang; Hu, Na; Yue, Lili

2015-02-14

An extended electronegativity equalization method/molecular mechanics (EEM/MM) model for ionic liquids is used to investigate the structures and properties of 1-alkyl-3-methylimidazolium glycine ionic liquids [C{sub n}mim][Gly] (n = 1–4) with alkyl substituents of different lengths. The EEM/MM model describes the electrostatic interactions of atoms and their changes in different ambient environments. This property is the most outstanding characteristic of the model. EEM parameters (i.e., valence electronegativities and valence hardness parameters) are calibrated using linear regression and least-squares methods, which can accurately predict the gas-phase properties of [C{sub n}mim]{sup +}, [Gly]{sup −}, and [C{sub n}mim][Gly] ion pairs. We utilize the EEM/MMmore » force field to systematically investigate the effects of polarizability on the accuracy of [C{sub n}mim][Gly] properties predicted through the molecular dynamic simulations. EEM/MM explicitly describes the atom-based polarizability of [C{sub n}mim][Gly]; thus, the densities, enthalpies of vaporization, self-diffusion coefficients, and conductivities of the [C{sub n}mim][Gly] are consistent with the experimental values. The calculated radial distribution functions provide a mechanistic understanding of the effects of polarizability on ionic aggregations in amino acid ionic liquids. The effects of alkyl chain length on the diffusion coefficient and conductivity are also discussed.« less

Resolving mass spectral overlaps in atom probe tomography by isotopic substitutions - case of TiSi15N.

PubMed

Engberg, David L J; Johnson, Lars J S; Jensen, Jens; Thuvander, Mattias; Hultman, Lars

2018-01-01

Mass spectral overlaps in atom probe tomography (APT) analyses of complex compounds typically limit the identification of elements and microstructural analysis of a material. This study concerns the TiSiN system, chosen because of severe mass-to-charge-state ratio overlaps of the 14 N + and 28 Si 2+ peaks as well as the 14 N 2 + and 28 Si + peaks. By substituting 14 N with 15 N, mass spectrum peaks generated by ions composed of one or more N atoms will be shifted toward higher mass-to-charge-state ratios, thereby enabling the separation of N from the predominant Si isotope. We thus resolve thermodynamically driven Si segregation on the nanometer scale in cubic phase Ti 1- x Si x 15 N thin films for Si contents 0.08 ≤ x ≤ 0.19 by APT, as corroborated by transmission electron microscopy. The APT analysis yields a composition determination that is in good agreement with energy dispersive X-ray spectroscopy and elastic recoil detection analyses. Additionally, a method for determining good voxel sizes for visualizing small-scale fluctuations is presented and demonstrated for the TiSiN system. Copyright © 2017 Elsevier B.V. All rights reserved.

Alkyl-substituted phenylamino derivatives of 7-nitrobenz-2-oxa-1,3-diazole as uncouplers of oxidative phosphorylation and antibacterial agents: involvement of membrane proteins in the uncoupling action.

PubMed

Antonenko, Yuri N; Denisov, Stepan S; Khailova, Ljudmila S; Nazarov, Pavel A; Rokitskaya, Tatyana; Tashlitsky, Vadim N; Firsov, Alexander M; Korshunova, Galina A; Kotova, Elena A

2017-03-01

In search for new effective uncouplers of oxidative phosphorylation, we studied 4-aryl amino derivatives of a fluorescent group 7-nitrobenz-2-oxa-1,3-diazol (NBD). In our recent work (Denisov et al., Bioelectrochemistry, 2014), NBD-conjugated alkyl amines (NBD-C n ) were shown to exhibit uncoupling activity. It was concluded that despite a pK a value being about 10, the expected hindering of the uncoupling activity could be overcome by insertion of an alkyl chain. There is evidence in the literature that the introduction of an aryl substituent in the 4-amino NBD group shifts the pK a to neutral values. Here we report the data on the properties of a number of 4-arylamino derivatives of NBD, namely, alkylphenyl-amino-NBD (C n -phenyl-NBD) with varying alkyl chain C n . By measuring the electrical current across planar bilayer lipid membrane, the protonophoric activity of C n -phenyl-NBD at neutral pH grew monotonously from C 1 - to C 6 -phenyl-NBD. All of these compounds increased the respiration rate and reduced the membrane potential of isolated rat liver mitochondria. Importantly, the uncoupling action of C 6 - and C 4 -phenyl-NBD was partially reversed by glutamate, diethyl pyrocarbonate (DEPC), 6-ketocholestanol, and carboxyatractyloside, thus pointing to the involvement of membrane proteins in the uncoupling activity of C n -phenyl-NBD in mitochondria. The pronounced recoupling effect of DEPC, an inhibitor of an aspartate-glutamate carrier (AGC), and that of its substrates for the first time highlighted AGC participation in the action of potent uncouplers on mitochondria. C 6 -phenyl-NBD produced strong antimicrobial effect on Bacillus subtilis, which manifested itself in cell membrane depolarization and suppression of bacterial growth at submicromolar concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel 4-Substituted-N,N-dimethyltetrahydronaphthalen-2-amines: Synthesis, Affinity, and In Silico Docking Studies at Serotonin 5-HT2-type and Histamine H1 G Protein-Coupled Receptors

PubMed Central

Sakhuja, Rajeev; Kondabolu, Krishnakanth; Córdova-Sintjago, Tania; Travers, Sean; Vincek, Adam S.; Kim, Myong Sang; Abboud, Khalil A.; Fang, Lijuan; Sun, Zhuming; Canal, Clinton E.; Booth, Raymond G.

2015-01-01

Syntheses were undertaken of derivatives of (2S, 4R)-(−)-trans-4-phenyl-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (4-phenyl-2-dimethylaminotetralin, PAT), a stereospecific agonist at the serotonin 5-HT2C G protein-coupled receptor (GPCR), with inverse agonist activity at 5-HT2A and 5-HT2B GPCRs. Molecular changes were made at the PAT C(4)-position, while preserving N, N-dimethyl substitution at the 2-position as well as trans-stereochemistry, structural features previously shown to be optimal for 5-HT2 binding. Affinities of analogs were determined at recombinant human 5-HT2 GPCRs in comparison to the phylogenetically closely-related histamine H1 GPCR, and in silico ligand docking studies were conducted at receptor molecular models to help interpret pharmacological results and guide future ligand design. In most cases, C(4)-substituted PAT analogs exhibited the same stereoselectivity ([−]-trans > [+]-trans) as the parent PAT across 5-HT2 and H1 GPCRs, albeit, with variable receptor selectivity. 4-(4′-substituted)-PAT analogs, however, demonstrated reversed stereoselectivity ([2S, 4R]-[+]-trans > [2S, 4R]-[−]-trans), with absolute configuration confirmed by single X-ray crystallographic data for the 4-(4′-Cl)-PAT analog. Pharmacological affinity results and computational results herein support further PAT drug development studies and provide a basis for predicting and interpreting translational results, including, for (+)-trans-4-(4′-Cl)-PAT and (−)-trans-4-(3′-Br)-PAT that were previously shown to be more potent and efficacious than their corresponding enantiomers in rodent models of psychoses, psychostimulant-induced behaviors, and compulsive feeding (‘binge-eating’). PMID:25703249

Alkyl radical generation by an intramolecular homolytic substitution reaction between iron (II) and trialkylsulfonium groups.

PubMed

Jungen, Stefan; Chen, Peter

2018-05-16

Intramolecular, homolytic substitution reactions between iron (II) species and various trialkylsulfonium groups were directly observed in the gas phase upon collision induced dissociation. In spite of the notoriously low reduction potential of trialkylsulfonium species and the mismatched oxidation potential of iron (II), the reactions proceed at moderate collision energies, forming an alkyl radical as well as a thioether coordinated to the iron. In contrast to classical homolytic substitutions, the attacking radical is a "metalloradical", namely iron (II) that is oxidized to iron (III) during the reaction. With this process we demonstrate that the conceptually analogous, putative radical generation step in Radical S-Adenosyl Methionine Enzymes is possible and plausible. Further, we show that this kind of reaction only occurs in constrained systems with a defined geometry. Combining experimental measurements with DFT studies and NBO analyses allowed us to gain insights into the reactivity and transition states of these systems. Based on our findings, we challenge the notion of a collinear transition state in the radical generation step of Radical SAM Enzymes and propose it to be bent instead. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Substituent Effects on the [N-I-N](+) Halogen Bond.

PubMed

Carlsson, Anna-Carin C; Mehmeti, Krenare; Uhrbom, Martin; Karim, Alavi; Bedin, Michele; Puttreddy, Rakesh; Kleinmaier, Roland; Neverov, Alexei A; Nekoueishahraki, Bijan; Gräfenstein, Jürgen; Rissanen, Kari; Erdélyi, Máté

2016-08-10

We have investigated the influence of electron density on the three-center [N-I-N](+) halogen bond. A series of [bis(pyridine)iodine](+) and [1,2-bis((pyridine-2-ylethynyl)benzene)iodine](+) BF4(-) complexes substituted with electron withdrawing and donating functionalities in the para-position of their pyridine nitrogen were synthesized and studied by spectroscopic and computational methods. The systematic change of electron density of the pyridine nitrogens upon alteration of the para-substituent (NO2, CF3, H, F, Me, OMe, NMe2) was confirmed by (15)N NMR and by computation of the natural atomic population and the π electron population of the nitrogen atoms. Formation of the [N-I-N](+) halogen bond resulted in >100 ppm (15)N NMR coordination shifts. Substituent effects on the (15)N NMR chemical shift are governed by the π population rather than the total electron population at the nitrogens. Isotopic perturbation of equilibrium NMR studies along with computation on the DFT level indicate that all studied systems possess static, symmetric [N-I-N](+) halogen bonds, independent of their electron density. This was further confirmed by single crystal X-ray diffraction data of 4-substituted [bis(pyridine)iodine](+) complexes. An increased electron density of the halogen bond acceptor stabilizes the [N···I···N](+) bond, whereas electron deficiency reduces the stability of the complexes, as demonstrated by UV-kinetics and computation. In contrast, the N-I bond length is virtually unaffected by changes of the electron density. The understanding of electronic effects on the [N-X-N](+) halogen bond is expected to provide a useful handle for the modulation of the reactivity of [bis(pyridine)halogen](+)-type synthetic reagents.

Synthesis of 7-azabicyclo[2.2.1]heptane and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives by base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides.

PubMed

Gómez-Sanchez, Elena; Soriano, Elena; Marco-Contelles, José

2007-11-09

We have studied the base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides, investigating the effect of the nitrogen protecting group and the relative configuration of the leaving group at C3 and C4 on the outcome of this reaction. We have observed that the sodium hydride-promoted heterocyclization of alkyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamates (10, 12, 14, 16, 18) is a convenient method for the synthesis of 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of tert-butyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamate (10) with sodium hydride in DMF at room temperature provides 2-bromo-7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]heptane (2) (52% yield), whose t-BuOK-promoted hydrogen bromide elimination affords 7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (31) in 78% yield, an intermediate in the total synthesis of epibatidine (1). However, the NaH/DMF-mediated heterocyclization of alkyl N-(trans-3,cis-4-dibromocyclohex-1-yl)carbamates (11, 13) is a more structure dependent reaction, where the nucleophilic attack of the oxygen atom of the protecting group controls the outcome of the reaction, giving rise to benzooxazolone and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, from low to moderate yields, in complex reaction mixtures. Conversely, the NaH/DMF heterocyclizations of N-(cis-3,trans-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (40) or N-(trans-3,cis-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (42) are very clean reactions giving 7-azabicyclo[2.2.1]heptane or 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, in good yields. Finally, a mechanistic investigation, based on DFT calculations, has been carried out to rationalize the formation of the different adducts.

15N nuclear magnetic resonance studies on the tautomerism of 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and other C8-substituted guanine nucleosides.

PubMed

Cho, B P; Kadlubar, F F; Culp, S J; Evans, F E

1990-01-01

The favored tautomeric and ionic structures were examined for the oxidative DNA damage adduct 8-hydroxy-2'-deoxyguanosine and its RNA analogue 8-hydroxyguanosine by 15N NMR spectroscopy. In addition, 15N chemical shifts and coupling constants from 13 different guanine nucleosides, including a wide variety of C8 substitutions (OH, SH, Br, OCH2C6H5, OCH3, SCH3, and SO2CH3), have been analyzed with respect to their tautomeric structures. A -98.5-Hz proton-nitrogen coupling constant observed for the N7 resonance of 8-hydroxyguanosine in dimethyl sulfoxide was evidence for 8-keto substitution, which is contrary to the structure implied by the generally used nomenclature. The pH dependence of 15N NMR spectra of 8-hydroxyguanosine in aqueous solution showed downfield shifts of the N1 and N7 resonances that were greater than 50 ppm, which indicated the conversion from a neutral 6,8-diketo to a 6-enolate-8-keto (pKa1 = 8.6) and finally to a 6,8-dienolate structure (pKa2 = 11.7). There was no evidence of an 8-enol substituent in the absence of ionization. It is proposed that the syn conformation of these oxidized bases in duplex DNA and RNA can be further stabilized by abnormal hydrogen bonding or mispairing that involves N7-H. The combined data show that 15N NMR is a sensitive probe to examine tautomerism of the guanine ring system. The analysis indicates that the change from a single to a double bond for the C8 substituent, and the accompanying removal of the normal double bond between N7 and C8 on the imidazole ring system, has no detectable effect on the tautomerism at the N1-O6 site of the pyrimidine ring system for both the 8-keto and 8-thio substitutions. In addition, large differences in electronegativity of the C8 substituents do not alter the N1-O6 tautomerism.

Fragmentation of negative ions from N-linked carbohydrates, part 4. Fragmentation of complex glycans lacking substitution on the 6-antenna.

PubMed

Harvey, David J; Jaeken, Jaak; Butler, Mike; Armitage, Alison J; Rudd, Pauline M; Dwek, Raymond A

2010-05-01

Negative ion CID spectra of N-linked glycans released from glycoproteins contain many ions that are diagnostic for specific structural features such as the detailed arrangement of antennae and the location of fucose residues. Identification of such ions requires reference glycans that are often difficult to acquire in a pure state. The recent acquisition of a sample of N-glycans from a patient lacking the enzyme N-acetylglucosaminyltransferase-2 provided an opportunity to investigate fragmentation of glycans lacking a 6-antenna. These glycans contained one or two galactose-N-acetylglucosamine-chains attached to the 3-linked mannose residue of the trimannosyl-chitobiose core with and without fucose substitution. The spectra from the patient sample clearly defined the antenna distribution and showed striking differences from the spectra of isomeric compounds obtained from normal subjects. Furthermore, they provided additional information on previously identified antenna-specific fragment ions and indicated the presence of additional ions that were diagnostic of fucose substitution. Glycans obtained from such enzyme-deficient patients can, thus, be a valuable way of obtaining spectra of specific isomers in a relatively pure state for interpretation of mass spectra. 2010 John Wiley & Sons, Ltd.

Fluorinated methacrylamide chitosan sequesters reactive oxygen species to relieve oxidative stress while delivering oxygen.

PubMed

Patil, Pritam S; Leipzig, Nic D

2017-08-01

Antioxidants play an important role in regulating overabundant reactive oxygen species (ROS) in wound healing to reduce oxidative stress and inflammation. In this work, we demonstrate for the first time that functionalization of methacrylamide chitosan (MAC) with aliphatic pentadecafluoro chains, to synthesize pentadecafluoro-octanoyl methacrylamide chitosan (MACF), enhances the antioxidant capacity of the MAC base hydrogel material, while being able to deliver oxygen for future enhanced wound healing applications. As such, MACF was shown to sequester more nitric oxide (p < 0.01) and hydroxyl (p < 0.0001) radicals as compared to the negative control even when delivering additional oxygen. MACF's beneficial antioxidant capacity was further confirmed in in vitro cell culture experiments using human dermal fibroblasts stressed with 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2368-2374, 2017. © 2017 Wiley Periodicals, Inc.

SOME SYSTEMS OF GENERATORS OF THE GROUP \\mathrm{GL}(n,\\,\\mathbb{Z}) FOR n\\leq5

NASA Astrophysics Data System (ADS)

Dress, A.; Ryshkov, S. S.

1994-02-01

It is proved geometrically that the groups \\mathrm{GL}(n,\\,\\mathbb{Z}), 0, are generated by systems of generators of finite groups G_n and, for each such n, one additional substitution h(n).Bibliography: 8 titles.

Photoinduced, Copper-Catalyzed Carbon-Carbon Bond Formation with Alkyl Electrophiles: Cyanation of Unactivated Secondary Alkyl Chlorides at Room Temperature.

PubMed

Ratani, Tanvi S; Bachman, Shoshana; Fu, Gregory C; Peters, Jonas C

2015-11-04

We have recently reported that, in the presence of light and a copper catalyst, nitrogen nucleophiles such as carbazoles and primary amides undergo C-N coupling with alkyl halides under mild conditions. In the present study, we establish that photoinduced, copper-catalyzed alkylation can also be applied to C-C bond formation, specifically, that the cyanation of unactivated secondary alkyl chlorides can be achieved at room temperature to afford nitriles, an important class of target molecules. Thus, in the presence of an inexpensive copper catalyst (CuI; no ligand coadditive) and a readily available light source (UVC compact fluorescent light bulb), a wide array of alkyl halides undergo cyanation in good yield. Our initial mechanistic studies are consistent with the hypothesis that an excited state of [Cu(CN)2](-) may play a role, via single electron transfer, in this process. This investigation provides a rare example of a transition metal-catalyzed cyanation of an alkyl halide, as well as the first illustrations of photoinduced, copper-catalyzed alkylation with either a carbon nucleophile or a secondary alkyl chloride.

Oxidative 1,2-carboamination of alkenes with alkyl nitriles and amines toward γ-amino alkyl nitriles

NASA Astrophysics Data System (ADS)

Liu, Yan-Yun; Yang, Xu-Heng; Song, Ren-Jie; Luo, Shenglian; Li, Jin-Heng

2017-04-01

Difunctionalization of alkenes has become a powerful tool for quickly increasing molecular complexity in synthesis. Despite significant progress in the area of alkene difunctionalization involving the incorporation of a nitrogen atom across the C-C double bonds, approaches for the direct 1,2-carboamination of alkenes to produce linear N-containing molecules are scarce and remain a formidable challenge. Here we describe a radical-mediated oxidative intermolecular 1,2-alkylamination of alkenes with alkyl nitriles and amines involving C(sp3)-H oxidative functionalization catalysed by a combination of Ag2CO3 with iron Lewis acids. This three-component alkene 1,2-alkylamination method is initiated by the C(sp3)-H oxidative radical functionalization, which enables one-step formation of two new chemical bonds, a C-C bond and a C-N bond, to selectively produce γ-amino alkyl nitriles.

Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, novel small molecule Hypoxia Inducible Factor-1 (HIF-1) pathway inhibitors and anti-cancer agents

PubMed Central

Mun, Jiyoung; Jabbar, Adnan Abdul; Devi, Narra Sarojini; Yin, Shaoman; Wang, Yingzhe; Tan, Chalet; Culver, Deborah; Snyder, James P.; Van Meir, Erwin G.; Goodman, Mark M.

2013-01-01

The Hypoxia Inducible Factor (HIF) pathway is an attractive target for cancer as it controls tumor adaptation to growth under hypoxia and mediates chemo- and radiation resistance. We previously discovered 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, as a novel small molecule HIF-1 pathway inhibitor in a high-throughput cell-based assay, but its in vivo delivery is hampered by poor aqueous solubility (0.009 μM in water; logP7.4: 3.7). Here we describe the synthesis of twelve N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, which were designed to possess optimal lipophilicities and aqueous solubilities by in silico calculations. Experimental logP7.4 values of 8 of the 12 new analogs ranged from 1.2 ∼ 3.1. Aqueous solubilities of 3 analogs were measured, among which the most soluble N-[(8-methoxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridine-2-sulfonamide had an aqueous solubility of 80 μM, e.g. a solubility improvement of ∼9,000-fold. The pharmacological optimization had minimal impact on drug efficacy as the compounds retained IC50 values at or below 5 μM in our HIF-dependent reporter assay. PMID:22746274

Activation of rhenium(I) toward substitution in fac-[Re(N,O'-Bid)(CO)3(HOCH3)] by Schiff-base bidentate ligands (N,O'-Bid).

PubMed

Brink, Alice; Visser, Hendrik G; Roodt, Andreas

2013-08-05

A series of fac-[Re(N,O'-Bid)(CO)3(L)] (N,O'-Bid = monoanionic bidentate Schiff-base ligands with N,O donor atoms; L = neutral monodentate ligand) has been synthesized, and the methanol substitution reactions have been investigated. The complexes were characterized by NMR, IR, and UV-vis spectroscopy. X-ray crystal structures of the compounds fac-[Re(Sal-mTol)(CO)3(HOCH3)], fac-[Re(Sal-pTol)(CO)3(HOCH3)], fac-[Re(Sal-Ph)(CO)3(HOCH3)], and fac-[Re(Sal-Ph)(CO)3(Py)] (Sal-mTol = 2-(m-tolyliminomethyl)phenolato; Sal-pTol = 2-(p-tolyliminomethyl)phenolato; Sal-Ph = 2-(phenyliminomethyl)phenolato; Py = pyridine) are reported. Significant activation for the methanol substitution is induced by the use of the N,O bidentate ligand as manifested by the second order rate constants, with limiting kinetics being observed for the first time. Rate constants (25 °C) (k1 or k3) and activation parameters (ΔHk‡, kJ mol(-1); ΔSk‡, J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as indicated are as follows: fac-[Re(Sal-mTol)(CO)3(HOCH3)] 3-chloropyridine: (k1) 2.33 ± 0.01 M(-1) s(-1); 85.1 ± 0.6, 48 ± 2; fac-[Re(Sal-mTol)(CO)3(HOCH3)] pyridine: (k1) 1.29 ± 0.02 M(-1) s(-1); 92 ± 2, 66 ± 7; fac-[Re(Sal-mTol)(CO)3(HOCH3)] 4-picoline: (k1) 1.27 ± 0.05 M(-1) s(-1); 88 ± 2, 53 ± 6; (k3) 3.9 ± 0.03 s(-1); 78 ± 8, 30 ± 27; (kf) 1.7 ± 0.02 M(-1) s(-1); 86 ± 2, 49 ± 6; fac-[Re(Sal-mTol)(CO)3(HOCH3)] DMAP (k3) 1.15 ± 0.02 s(-1); 88 ± 2, 52 ± 7. An interchange dissociative mechanism is proposed.

40 CFR 721.5288 - Chromate(2-), [3-hydroxy-4-[(2-hydroxy-1-naphthenyl)azo]-7-nitro-1-substituted][N-[7-hydroxy-8...

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.5288 Chromate(2-), [3-hydroxy-4-[(2-hydroxy-1-naphthenyl)azo]-7-nitro-1-substituted][N-[7-hydroxy-8-[(2-hydroxy-5-nitrophenyl)azo]-1-substituted]-, salt (generic). (a) Chemical...

Primary amino acid derivatives: substitution of the 4'-N'-benzylamide site in (R)-N'-benzyl 2-amino-3-methylbutanamide, (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide, and (R)-N'-benzyl 2-amino-3-methoxypropionamide provides potent anticonvulsants with pain-attenuating properties.

PubMed

King, Amber M; Salomé, Christophe; Salomé-Grosjean, Elise; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Stables, James P; Kohn, Harold

2011-10-13

Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED(50) = 13-21 mg/kg) exceeded those of phenobarbital (ED(50) = 22 mg/kg). Two additional studies defining the structure-activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (∼4-fold) increase in activity (ED(50) = 8.9 mg/kg), a value that surpassed phenytoin (ED(50) = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.

Structure-activity relationships for hallucinogenic N,N-dialkyltryptamines: photoelectron spectra and serotonin receptor affinities of methylthio and methylenedioxy derivatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kline, T.B.; Benington, F.; Morin, R.D.

1982-11-01

Serotonin receptor affinity and photelectron spectral data were obtained on a number of substituted N,N-dimethyltryptamines. Evidence is presented that electron-donating substituents in the 5-position lead to enhanced behavioral disruption activity and serotonin receptor affinity as compared to unsubstituted N,N-dimethyltryptamine and analogues substituted in the 4- or 6-position. Some correlation was found between ionization potentials and behavioral activity, which may have implications concerning the mechanism of receptor binding.

Design and Synthesis of N6-Substituted-4′-thioadenosine-5′-uronamides As Potent and Selective Human A3 Adenosine Receptor Agonists

PubMed Central

Choi, Won Jun; Lee, Hyuk Woo; Kim, Hea Ok; Chinn, Moshe; Gao, Zhan-Guo; Patel, Amit; Jacobson, Kenneth A.; Moon, Hyung Ryong; Jung, Young Hoon; Jeong, Lak Shin

2009-01-01

On the basis of a bioisosteric rationale, 4′-thionucleoside analogues of IB-MECA, which is a potent and selective A3 adenosine receptor agonist (AR), were synthesized from d-gulonic acid γ-lactone. The 4′-thio analogue (5h) of IB-MECA showed extremely high binding affinity (Ki = 0.25 nM) at the human A3AR and was more potent than IB-MECA (Ki = 1.4 nM). Bulky substituents at the 5′-uronamide position, such as cyclohexyl and 2- methylbenzyl, in this series of 2-H nucleoside derivatives were tolerated in A3AR binding, although small alkyl analogues were more potent. PMID:19879151

Charge transport in fibre-based perylene-diimide transistors: effect of the alkyl substitution and processing technique.

PubMed

Savage, Rebecca C; Orgiu, Emanuele; Mativetsky, Jeffrey M; Pisula, Wojciech; Schnitzler, Tobias; Eversloh, Christian Lütke; Li, Chen; Müllen, Klaus; Samorì, Paolo

2012-04-07

We report a comparative study on the self-assembly from solution and electrical characterization of n-type semiconducting fibres obtained from five different perylenebis(dicarboximide) (PDI) derivatives. In particular we investigated the role of the nature of the alkyl chain covalently linked to the N,N' sites of the PDI in modulating the molecular solubility and aggregation capacity. We explored the morphologies of the self-assembled architectures physisorbed on dielectric surfaces and in particular how they can be modified by tuning the deposition and post-deposition procedures, i.e. by modulating the kinetics of the self-assembly process. To this end, alongside the conventional spin-coating, solvent vapour annealing (SVA) and solvent induced precipitation (SIP) have been employed. Both approaches led to fibres having widths of several hundred nanometres and lengths up to tens of micrometres. SVA formed isolated fibres which were tens of nanometres high, flat, and tapered at the ends. Conversely, SIP fibres exhibited nearly matching heights and widths, but organized into bundles. Despite these morphological differences, the same intermolecular packing is found by XRD in each type of structure, albeit with differing degrees of long-range order. The study of the electrical characteristics of the obtained low dimensional nano-assemblies has been accomplished by fabricating and characterizing organic field-effect transistors. This journal is © The Royal Society of Chemistry 2012

[Polymethylene derivatives of nucleic bases with omega-functional groups: VII. Cytotoxicity in the series of N-(2-oxocyclohexyl)-omega-oxoalkyl substituted purines and pyrimidines].

PubMed

Komissarov, V V; Volgareva, G M; Ol'shanskaia, Ia S; Chernyshova, M E; Zavalishina, L E; Frank, G A; Shtil', A A; Kritsyn, A M

2009-01-01

New polymethylene derivatives of nucleic bases with a beta-diketo function in the omega-position were obtained by alkylation of uracil, thymine, cytosine, hypoxanthine, adenine, and N(2)-isobutyryl guanine with 2-omega-chloroal-kanoyl)cyclohexanones. The physical and chemical characteristics of the compounds synthesized and their effect on the K562 and HCT116 tumor cell lines were studied.

Combustion Properties of Amino-Substituted Guanidinium 4,4',5,5'-Tetranitro-2,2'-biimidazolate(N4BIM) Salts

DOE PAGES

Tappan, Bryce C.; Chavez, David E.

2014-12-02

This paper describes the combustion properties of the amino-substituted guanidinium 4,4’,5,5’-tetranitro-2,2’-biimidazolate (N4BIM) series, including the bis-mono, di and triaminoguanidinium salts. These salts are of interest as propellant ingredient additives, and in particular, the bis-triaminoguanidinium salt of N4BIM displays excellent burn rate and combustion behavior. Our combustion studies have shown that TAGN4-BIM displays a fast burning rate and has the lowest pressure dependence exponent yet measured for a triaminoguanidinium salt.

Direct dehydroxytrifluoromethylthiolation of alcohols using silver(I) trifluoromethanethiolate and tetra-n-butylammonium iodide.

PubMed

Liu, Jian-Bo; Xu, Xiu-Hua; Chen, Zeng-Hao; Qing, Feng-Ling

2015-01-12

An unprecedented reaction for the direct trifluoromethylthiolation and fluorination of alkyl alcohols using AgSCF3 and nBu4NI has been developed. The trifluoromethylthiolated compounds and alkyl fluorides were selectively formed by changing the ratio of AgSCF3/nBu4NI. This protocol is tolerant of different functional groups and might be applicable to late-stage trifluoromethylthiolation of alcohols. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and serotonergic activity of substituted 2, N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N, N-dimethyltryptamine derivatives: novel antagonists for the vascular 5-HT(1B)-like receptor.

PubMed

Moloney, G P; Martin, G R; Mathews, N; Milne, A; Hobbs, H; Dodsworth, S; Sang, P Y; Knight, C; Williams, M; Maxwell, M; Glen, R C

1999-07-15

The synthesis and vascular 5-HT(1B)-like receptor activity of a novel series of substituted 2, N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N, N-dimethyltryptamine derivatives are described. Modifications to the 5-ethylene-linked heterocycle and to substituents on the 2-benzylamide side chain have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT(1B)-like receptor of pK(B) > 7.0, up to 100-fold selectivity over alpha(1)-adrenoceptor affinity and 5-HT(2A) receptor affinity, and which exhibited a favorable pharmacokinetic profile. N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2, 5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxamide (23) was identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5-HT(1B)-like receptor-mediated agonist activity in the rabbit femoral artery), and competitive vascular 5-HT(1B)-like receptor antagonist with a plasma elimination half-life of approximately 4 h in dog plasma and with good oral bioavailability. The selectivity of compounds from this series for the vascular 5-HT(1B)-like receptors over other receptor subtypes is discussed as well as a proposed mode of binding to the receptor pharmacophore. It has been proposed that the aromatic ring of the 2, N-benzylcarboxamide group can occupy an aromatic binding site rather than the indole ring. The resulting conformation allows an amine-binding site to be occupied by the ethylamine nitrogen and a hydrogen-bonding site to be occupied by one of the hydantoin carbonyls. The electronic nature of the 2,N-benzylcarboxamide aromatic group as well as the size of substituents on this aromatic group is crucial for producing potent and selective antagonists. The structural requirement on the 3-ethylamine side chain incorporating the protonatable nitrogen is achieved by the bulky 2, N-benzylcarboxamide group and its close proximity to the 3-side chain.

Synthesis, characterization and photophysical-theoretical analysis of compounds A-π-D. 1. Effect of alkyl-phenyl substituted amines in photophysical properties

NASA Astrophysics Data System (ADS)

Ortega, E.; Montecinos, R.; Cattin, L.; Díaz, F. R.; del Valle, M. A.; Bernède, J. C.

2017-08-01

The study of new dipolar A-π-D molecules, which have an acceptor (A) and donor (D) charge joined by a conjugate bridge, have been an attention focus in the recent years due their different properties. In the current work, a molecular system has been modified in order to compare the effect on properties, such as quantum yield. Thus, two series were generated (alkyl- and alkoxy-substituted) to determine if molecules with tertiary asymmetric amines change their optical properties and whether quantum yield is affected. The different products have been characterized by several techniques such as UV-Vis spectrophotometry, elemental analysis, NMR, FT-IR, mass spectroscopy and fluorescence spectroscopy. Furthermore, their behavior in eight organic solvents, dichloromethane, tetrahydrofuran, ethyl acetate, 1,4-dioxane, acetone, acetonitrile, dimethylformamide and dimethylsulfoxide were experimentally and theoretically studied. The quantum yields were higher for the alkyl-substituted series. Theoretically, the dihedral angles formed between the tertiary amine and carbonyl group moieties have a correlation with quantum yield values, helping to explain why they are higher in non-polar solvents. Consequently, the maximum quantum yield was obtained with (E)-2-cyano-3-(5-((E)-2-(9,9-diethyl-7-(methyl(phenyl)amino)-9H-fluoren-2-yl) vinyl)thiophen-2-yl)acrylic acid (M8-1) in 1,4-dioxane, reaching 98.8%.

Spin labeled antioxidants protect bacteria against the toxicity of alkylating antitumor drug CCNU.

PubMed

Gadjeva, Vesselina; Lazarova, Grozdanka; Zheleva, Antoaneta

2003-10-15

We have studied the toxic effect of the alkylating antitumor drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU) on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) strains, alone and in presence of oxygen radical-scavenging substances [Vitamin E, stable nitroxyl radical 2,2,6,6-tetramethylpiperidine-N-oxyl (TMPO), and spin labeled (nitroxyl free radical moiety containing) analogues of CCNU] and compared with that of the alkylating antitumor drug 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (dacarbazine, DTIC). All spin labeled compounds tested were almost no toxic at doses of 50-500 microM/ml, whereas the alkylating antitumor drug CCNU showed toxicity in a dose dependent manner. Even low doses of spin labeled nitrosoureas provided protection against the toxicity caused by the antitumor drug CCNU alone. The lowest toxicity against E. coli and S. aureus were achieved when 500 microM/ml of CCNU was combined with 200 microM/ml of spin labeled nitrosourea N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-glycine amid of 2,2,6,6-tetramethyl-4-aminopiperidine-1-oxyl (SLCNUgly). A combination of TMPO with vitamin E completely abolished the toxicity of CCNU. Endogenous formation of oxygen radicals and their possible involvement in CCNU toxicity towards the bacteria strains tested have been also discussed.

Multipotent MAO and cholinesterase inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of heterocyclic substituted alkyl and cycloalkyl propargyl amine.

PubMed

Samadi, Abdelouahid; de los Ríos, Cristóbal; Bolea, Irene; Chioua, Mourad; Iriepa, Isabel; Moraleda, Ignacio; Bartolini, Manuela; Andrisano, Vincenza; Gálvez, Enrique; Valderas, Carolina; Unzeta, Mercedes; Marco-Contelles, José

2012-06-01

The synthesis, pharmacological evaluation and molecular modeling of heterocyclic substituted alkyl and cycloalkyl propargyl amines 1-7 of type I, and 9-12 of type II, designed as multipotent inhibitors able to simultaneously inhibit monoamine oxidases (MAO-A/B) as well as cholinesterase (AChE/BuChE) enzymes, as potential drugs for the treatment of Alzheimer's disease, are described. Indole derivatives 1-7 of type I are well known MAO inhibitors whose capacity to inhibit AChE and BuChE was here investigated for the first time. As a result, compound 7 was identified as a MAO-B inhibitor (IC(50) = 31 ± 2 nM) and a moderately selective eqBuChE inhibitor (IC(50) = 4.7 ± 0.2 μM). Conversely, the new and readily available 5-amino-7-(prop-2-yn-1-yl)-6,7,8,9-tetrahydropyrido[2,3-b][1,6]naphthyridine derivatives 9-13 of type II are poor MAO inhibitors, but showed AChE selective inhibition, compound 12 being the most attractive as it acts as a non-competitive inhibitor on EeAChE (IC(50) = 25 ± 3 nM, K(i) = 65 nM). The ability of this compound to interact with the AChE peripheral binding site was confirmed by kinetic studies and by molecular modeling investigation. Studies on human ChEs confirmed that 12 is a selective AChE inhibitor with inhibitory potency in the submicromolar range. Moreover, in agreement with its mode of action, 12 was shown to be able to inhibit Aβ aggregation induced by hAChE by 30.6%. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Comparing Medline citations using modified N-grams.

PubMed

Nawab, Rao Muhammad Adeel; Stevenson, Mark; Clough, Paul

2014-01-01

We aim to identify duplicate pairs of Medline citations, particularly when the documents are not identical but contain similar information. Duplicate pairs of citations are identified by comparing word n-grams in pairs of documents. N-grams are modified using two approaches which take account of the fact that the document may have been altered. These are: (1) deletion, an item in the n-gram is removed; and (2) substitution, an item in the n-gram is substituted with a similar term obtained from the Unified Medical Language System Metathesaurus. N-grams are also weighted using a score derived from a language model. Evaluation is carried out using a set of 520 Medline citation pairs, including a set of 260 manually verified duplicate pairs obtained from the Deja Vu database. The approach accurately detects duplicate Medline document pairs with an F1 measure score of 0.99. Allowing for word deletions and substitution improves performance. The best results are obtained by combining scores for n-grams of length 1-5 words. Results show that the detection of duplicate Medline citations can be improved by modifying n-grams and that high performance can also be obtained using only unigrams (F1=0.959), particularly when allowing for substitutions of alternative phrases.

Discovery of novel and potent small-molecule inhibitors of NO and cytokine production as antisepsis agents: synthesis and biological activity of alkyl 6-(N-substituted sulfamoyl)cyclohex-1-ene-1-carboxylate.

PubMed

Yamada, Masami; Ichikawa, Takashi; Ii, Masayuki; Sunamoto, Mie; Itoh, Katsumi; Tamura, Norikazu; Kitazaki, Tomoyuki

2005-11-17

To develop a new therapeutic agent for sepsis, screening of the Takeda chemical library was carried out using mouse macrophages stimulated with lipopolysaccharide (LPS) to identify a new class of small-molecule inhibitors of inflammatory mediator production. The lead compound 5a was discovered, from which a series of novel cyclohexene derivatives I bearing a sulfamoyl and ester group were designed, synthesized and tested for their inhibitory activity against nitric oxide (NO) production. Derivatives I were synthesized by the coupling of sulfonyl chlorides and anilines with concomitant double bond migration in the presence of triethylamine, and phenyl ring substitution and modification of the ester and cyclohexene moieties were carried out. Among the compounds synthesized, ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate [(R)-(+)-5n, TAK-242] was found to exhibit the most potent suppressive activity for the production of not only NO but also inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) induced by LPS-stimulated mouse macrophages with IC50 values of 1.8, 1.9 and 1.3 nM, respectively. It shows marked beneficial effects in vivo also. Intravenous administration of (R)-(+)-5n at doses of 0.1 mg/kg or more suppressed the production of NO and various cytokines [TNF-alpha, IL-6 and IL-1beta] in the mouse endotoxin shock model. Furthermore, it protected mice from death dose-dependently and all mice survived at a dose of 3 mg/kg. The minimum effective dose to protect mice from lethality in this model was 0.3 mg/kg, which was consistent with those for inhibitory effects on the production of NO and cytokines. Compound (R)-(+)-5n is currently undergoing clinical trials for the treatment of sepsis.

Synthesis, characterization, and the antioxidant activity of N,N,N-trimethyl chitosan salts.

PubMed

Zhang, Jingjing; Tan, Wenqiang; Wang, Gang; Yin, Xiuli; Li, Qing; Dong, Fang; Guo, Zhanyong

2018-06-05

Chitosan, possessing excellent properties, has been drawing broad attention. For the further utilization of chitosan, chemical modification is performed in improving its water solubility and the bioactivities. In the current study, four N,N,N-trimethyl chitosan salts, including N,N,N-trimethyl chitosan citrate (TMCSCi), N,N,N-trimethyl chitosan acetylsalicylate (TMCSAc), N,N,N-trimethyl chitosan ascorbate (TMCSAs), and N,N,N-trimethyl chitosan gallate (TMCSGa), were prepared via N,N,N-trimethyl chitosan iodide (TMCSI). The as-prepared products were characterized by FT-IR and 1 H NMR. Meanwhile, the degrees of substitution were calculated by elemental analysis results. Furthermore, scavenging activities (against DPPH radicals and superoxide radicals) test and reducing power test were selected to evaluate the antioxidant property of N,N,N-trimethyl chitosan salts in vitro. The results indicated that TMCSAs and TMCSGa displayed excellent activity, probably due to the enhancement of ascorbate and gallate in antioxidant activity. However, because of the weak antioxidant property of citrate and acetylsalicylate, the activity was lower for TMCSCi and TMCSAc. For example, in the DPPH radicals scavenging assay, the scavenging rates of chitosan, TMCSI, TMCSCi, TMCSAc, TMCSAs, and TMCSGa were 25.22, 84.11, 6.90, 2.70, 94.92, and 96.75% at 0.4 mg/mL, respectively. Generally, TMCSAs and TMCSGa could be regarded as a potential source of antioxidants. Copyright © 2017. Published by Elsevier B.V.

Tunneling in hydrogen-transfer isomerization of n-alkyl radicals.

PubMed

Sirjean, Baptiste; Dames, Enoch; Wang, Hai; Tsang, Wing

2012-01-12

The role of quantum tunneling in hydrogen shift in linear heptyl radicals is explored using multidimensional, small-curvature tunneling method for the transmission coefficients and a potential energy surface computed at the CBS-QB3 level of theory. Several one-dimensional approximations (Wigner, Skodje and Truhlar, and Eckart methods) were compared to the multidimensional results. The Eckart method was found to be sufficiently accurate in comparison to the small-curvature tunneling results for a wide range of temperature, but this agreement is in fact fortuitous and caused by error cancellations. High-pressure limit rate constants were calculated using the transition state theory with treatment of hindered rotations and Eckart transmission coefficients for all hydrogen-transfer isomerizations in n-pentyl to n-octyl radicals. Rate constants are found in good agreement with experimental kinetic data available for n-pentyl and n-hexyl radicals. In the case of n-heptyl and n-octyl, our calculated rates agree well with limited experimentally derived data. Several conclusions made in the experimental studies of Tsang et al. (Tsang, W.; McGivern, W. S.; Manion, J. A. Proc. Combust. Inst. 2009, 32, 131-138) are confirmed theoretically: older low-temperature experimental data, characterized by small pre-exponential factors and activation energies, can be reconciled with high-temperature data by taking into account tunneling; at low temperatures, transmission coefficients are substantially larger for H-atom transfers through a five-membered ring transition state than those with six-membered rings; channels with transition ring structures involving greater than 8 atoms can be neglected because of entropic effects that inhibit such transitions. The set of computational kinetic rates were used to derive a general rate rule that explicitly accounts for tunneling. The rate rule is shown to reproduce closely the theoretical rate constants.

Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds.

PubMed

Pain, Anindita; Samanta, Suva; Dutta, Sushanta; Saxena, Ajit K; Shanmugavel, Mutiah; Sharma, Madhunika; Qazi, Gulam N; Sanyal, Utpal

2007-01-01

Four new ethylnitrosourea derivatives of substituted naphthalimides 3a-d have been synthesized from the respective N-(2-ethylamino) naphthalimides. Their chemical alkylating activity compared with the clinical drug CCNU and an experimental compound Mitonafide indicated that they possess lower alkylating activity than CCNU and comparable activity with the latter. Their anti-tumor efficacies were assessed in vivo in two murine ascites tumors namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. CCNU and Mitonafide were used as positive controls for comparison. The representative compound 3a has displayed marginal anti-tumoral activity in these tumors. Three compounds were further screened in vitro in 4 different human tumor cell lines but no significant activity was observed in those lines. These compounds moderately inhibit the synthesis of DNA and RNA in S-180 tumor cells.

Probing N-methyl-D-aspartate receptor desensitization with the substituted-cysteine accessibility method.

PubMed

Thomas, Christopher G; Krupp, Johannes J; Bagley, Elena E; Bauzon, Reginald; Heinemann, Stephen F; Vissel, Bryce; Westbrook, Gary L

2006-04-01

Several forms of macroscopic N-methyl-D-aspartate (NMDA) receptor desensitization affect the amplitude and duration of postsynaptic responses. In addition to its functional significance, desensitization provides one means to examine the conformational coupling of ligand binding to channel gating. Segments flanking the ligand binding domain in the extracellular N terminus of the NMDA receptor NR2 subunit influence the glycine-independent form of desensitization. The NR2A pre-M1 region, the linker between the glutamate binding domain and the channel pore, plays a critical role in desensitization. Thus, we used the substituted-cysteine accessibility method to scan the accessibility of residues in the pre-M1 region and the first transmembrane domain (M1) of NR2A. Cysteine mutants were expressed with NR1 in human embryonic kidney 293 cells and were assayed by whole-cell recording. With activation of the receptor by glutamate and glycine, only a single mutant, V557C, which is located at the beginning of M1, led to irreversible inhibition by the methanethiosulfonate derivative methanethiosulfonate ethyltrimethylammonium (MTSET). The NR2 ligand glutamate was insufficient on its own to induce modification of V557C by MTSET, suggesting that the change in accessibility required channel gating. The rate of MTSET modification of the homologous residue on NR1 (NR1-1a(L562C)/NR2A) was much slower than V557C. We also substituted cysteine in the V557 site of mutant subunits that exhibit either enhanced or reduced desensitization. Modification by MTSET correlated with the degree of desensitization for these subunits, suggesting that V557C is a sensitive detector of desensitization gating.

Lipase-Catalyzed Kinetic Resolution of Novel Antifungal N-Substituted Benzimidazole Derivatives.

PubMed

Łukowska-Chojnacka, Edyta; Staniszewska, Monika; Bondaryk, Małgorzata; Maurin, Jan K; Bretner, Maria

2016-04-01

A series of new N-substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase-catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100). © 2016 Wiley Periodicals, Inc.

Allylic Amination and N-Arylation-Based Domino Reactions Providing Rapid Three-Component Strategies to Fused Pyrroles with Different Substituted Patterns

PubMed Central

Jiang, Bo; Li, Ying; Tu, Man-Su; Wang, Shu-Liang; Tu, Shu-Jiang; Li, Guigen

2012-01-01

New three-component domino reaction providing divergent approaches to multi-functionalized fused pyrroles with different substituted patterns have been established (40 examples). The direct C(sp3)–N bond formation was achieved through intermolecular allylic amination in a one-pot operation; and N-arylation of amines was realized by varying N-amino acid enaminones. The reaction is easy to perform simply by mixing three common reactants in acetic acid under microwave heating. The reaction proceeds at fast rates and can be finished within 30 min, which makes workup convenient to give good chemical yields. PMID:22852549

Binding of alkylphenols and alkylated non-phenolics to the rainbow trout (Oncorhynchus mykiss) plasma sex steroid-binding protein.

PubMed

Tollefsen, K-E

2007-09-01

Alkylphenols are well-known endocrine disrupters, mediating effects through the estrogen receptor (ER). Although the estrogenic properties of the alkylphenols are well documented, alternative mechanisms of action are poorly described. In the present work, the interaction of a range of alkyl-substituted phenols and alkyl-substituted non-phenolics with the rainbow trout (Oncorhynchus mykiss) sex steroid-binding protein (rtSBP) were determined by competitive ligand-binding studies. The role of alkyl chain length and branching, substituent position, number of alkylated groups, and the requirement of a phenolic ring structure were assessed. The results showed that the rtSBP binds to most chemical structures tested, although the highest affinity was obtained for mono-substituted alkylphenols with a chain length of four to eight methyl groups. Interestingly, rtSBP binding was also observed for non-phenolic compounds such as 4-t-butylcyclohexanol and 4-t-butylnitrobenzene suggesting that the rtSBP has a broad binding specificity for alkylphenols and alkylated non-phenolics.

Enantiomerically Pure Acetals in Organic Synthesis: Resolutions and Diastereoselective Alkylations of Alpha-Hydroxy Esters

DTIC Science & Technology

1990-01-01

sensitivity of the alkylating agent to the reaction conditions. In either case , a decision was made to use 5-iodo-2- methyl -l-pentene as the alkylating ...agent, and the reaction conditions. In most cases the diastereomeric products of the alkylation were also separated by column chromatography. This...equatorially substituted product. Oxidation of the alcohol to the ketone followed by treatment with an alkyl Grignard reagent gave only the product which

Enhanced Piezoelectric Response of AlN via CrN Alloying

NASA Astrophysics Data System (ADS)

Manna, Sukriti; Talley, Kevin R.; Gorai, Prashun; Mangum, John; Zakutayev, Andriy; Brennecka, Geoff L.; Stevanović, Vladan; Ciobanu, Cristian V.

2018-03-01

Since AlN has emerged as an important piezoelectric material for a wide variety of applications, efforts have been made to increase its piezoelectric response via alloying with transition metals that can substitute for Al in the wurtzite lattice. We report on density functional theory calculations of structure and properties of the Crx Al1 -x N system for Cr concentrations ranging from zero to beyond the wurtzite-rocksalt transition point. By studying the different contributions to the longitudinal piezoelectric coefficient, we propose that the physical origin of the enhanced piezoelectricity in Crx Al1 -x N alloys is the increase of the internal parameter u of the wurtzite structure upon substitution of Al with the larger Cr ions. Among a set of wurtzite-structured materials, we find that Crx Al1 -x N has the most sensitive piezoelectric coefficient with respect to alloying concentration. Based on these results, we propose that Crx Al1 -x N is a viable piezoelectric material whose properties can be tuned via Cr composition. We support this proposal by combinatorial synthesis experiments, which show that Cr can be incorporated in the AlN lattice up to 30% before a detectable transition to rocksalt occurs. At this Cr content, the piezoelectric modulus d33 is approximately 4 times larger than that of pure AlN. This finding, combined with the relative ease of synthesis under nonequilibrium conditions, may position Crx Al1 -x N as a prime piezoelectric material for applications such as resonators and acoustic wave generators.

Enhanced Piezoelectric Response of AlN via CrN Alloying

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manna, Sukriti; Talley, Kevin R.; Gorai, Prashun

2018-03-01

Since AlN has emerged as an important piezoelectric material for a wide variety of applications, efforts have been made to increase its piezoelectric response via alloying with transition metals that can substitute for Al in the wurtzite lattice. We report on density functional theory calculations of structure and properties of the CrxAl1-xN system for Cr concentrations ranging from zero to beyond the wurtzite-rocksalt transition point. By studying the different contributions to the longitudinal piezoelectric coefficient, we propose that the physical origin of the enhanced piezoelectricity in CrxAl1-xN alloys is the increase of the internal parameter u of the wurtzite structuremore » upon substitution of Al with the larger Cr ions. Among a set of wurtzite-structured materials, we find that CrxAl1-xN has the most sensitive piezoelectric coefficient with respect to alloying concentration. Based on these results, we propose that CrxAl1-xN is a viable piezoelectric material whose properties can be tuned via Cr composition. We support this proposal by combinatorial synthesis experiments, which show that Cr can be incorporated in the AlN lattice up to 30% before a detectable transition to rocksalt occurs. At this Cr content, the piezoelectric modulus d33 is approximately 4 times larger than that of pure AlN. This finding, combined with the relative ease of synthesis under nonequilibrium conditions, may position CrxAl1-xN as a prime piezoelectric material for applications such as resonators and acoustic wave generators.« less

Sequential Metabolism of Secondary Alkyl Amines to Metabolic-Intermediate Complexes: Opposing Roles for the Secondary Hydroxylamine and Primary Amine Metabolites of Desipramine, (S)-Fluoxetine, and N-Desmethyldiltiazem

PubMed Central

Hanson, Kelsey L.; VandenBrink, Brooke M.; Babu, Kantipudi N.; Allen, Kyle E.; Nelson, Wendel L.

2010-01-01

Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hydroxyfluoxetine, and N-hydroxy-N-desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N-desmethyldesipramine, (S)-norfluoxetine, and N,N-didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine ≫ primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N-dealkylation to N-hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [(S)-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N-methyl-d3-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N-demethylation to N-hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N-hydroxylation rather than N-dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation. PMID:20200233

Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (s)-fluoxetine, and N-desmethyldiltiazem.

PubMed

Hanson, Kelsey L; VandenBrink, Brooke M; Babu, Kantipudi N; Allen, Kyle E; Nelson, Wendel L; Kunze, Kent L

2010-06-01

Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hydroxyfluoxetine, and N-hydroxy-N-desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N-desmethyldesipramine, (S)-norfluoxetine, and N,N-didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine > primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N-dealkylation to N-hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [(S)-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N-methyl-d(3)-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N-demethylation to N-hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N-hydroxylation rather than N-dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation.

Novel N-substituted aminobenzamide scaffold derivatives targeting the dipeptidyl peptidase-IV enzyme.

PubMed

Al-Balas, Qosay A; Sowaileh, Munia F; Hassan, Mohammad A; Qandil, Amjad M; Alzoubi, Karem H; Mhaidat, Nizar M; Almaaytah, Ammar M; Khabour, Omar F

2014-01-01

The dipeptidyl peptidase-IV (DPP-IV) enzyme is considered a pivotal target for controlling normal blood sugar levels in the body. Incretins secreted in response to ingestion of meals enhance insulin release to the blood, and DPP-IV inactivates these incretins within a short period and stops their action. Inhibition of this enzyme escalates the action of incretins and induces more insulin to achieve better glucose control in diabetic patients. Thus, inhibition of this enzyme will lead to better control of blood sugar levels. In this study, computer-aided drug design was used to help establish a novel N-substituted aminobenzamide scaffold as a potential inhibitor of DPP-IV. CDOCKER software available from Discovery Studio 3.5 was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the DPP-IV enzyme. The designed compounds were synthesized and tested against a DPP-IV enzyme kit provided by Enzo Life Sciences. The synthesized compounds were characterized using proton and carbon nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and determination of melting point. Sixty-nine novel compounds having an N-aminobenzamide scaffold were prepared, with full characterization. Ten of these compounds showed more in vitro activity against DPP-IV than the reference compounds, with the most active compounds scoring 38% activity at 100 μM concentration. The N-aminobenzamide scaffold was shown in this study to be a valid scaffold for inhibiting the DPP-IV enzyme. Continuing work could unravel more active compounds possessing the same scaffold.

Catalysis of hydrolysis and nucleophilic substitution at the P-N bond of phosphoimidazolide-activated nucleotides in phosphate buffers

NASA Technical Reports Server (NTRS)

Kanavarioti, A.; Rosenbach, M. T.

1991-01-01

Phosphoimidazolide-activated derivatives of guanosine and cytidine 5'-monophosphates, henceforth called ImpN's, exhibit enhanced rates of degradation in the presence of aqueous inorganic phosphate in the range 4.0 < or = pH < or = 8.6. This degradation is been attributed to (i) nucleophilic substitution of the imidazolide and (ii) catalysis of the P-N bond hydrolysis by phosphate. The first reaction results in the formation of nucleoside 5'-diphosphate and the second in nucleoside 5'-monophosphate. Analysis of the observed rates as well as the product ratios as a function of pH and phosphate concentration allow distinction between various mechanistic possibilities. The results show that both H2PO4- and HPO4(2-) participate in both hydrolysis and nucleophilic substitution. Statistically corrected biomolecular rate constants indicate that the dianion is 4 times more effective as a general base than the monoanion, and 8 times more effective as nucleophile. The low Bronsted value beta = 0.15 calculated for these phosphate species, presumed to act as general bases in facilitating water attack, is consistent with the fact that catalysis of the hydrolysis of the P-N bond in ImpN's has not been detected before. The beta nuc = 0.35 calculated for water, H2PO4-, HPO4(2-), and hydroxide acting as nucleophiles indicates a more associative transition state for nucleotidyl (O2POR- with R = nucleoside) transfers than that observed for phosphoryl (PO3(2-)) transfers (beta nuc = 0.25). With respect to the stability/reactivity of ImpN's under prebiotic conditions, our study shows that these materials would not suffer additional degradation due to inorganic phosphate, assuming the concentrations of phosphate, Pi, on prebiotic Earth were similar to those in the present oceans ([Pi] approximately 2.25 micromoles).

2-Hydroxyethyl substituted NHC precursors: Synthesis, characterization, crystal structure and carbonic anhydrase, α-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties

NASA Astrophysics Data System (ADS)

Erdemir, Fatoş; Barut Celepci, Duygu; Aktaş, Aydın; Taslimi, Parham; Gök, Yetkin; Karabıyık, Hasan; Gülçin, İlhami

2018-03-01

This study contains novel a serie synthesis of N-heterocyclic carbene (NHC) precursors that 2-hydroxyethyl substituted. The NHC precursors have been prepared from 1-(2- hydroxyethyl)benzimidazole and alkyl halides. The novel NHC precursors have been characterized by using 1H NMR, 13C NMR, FTIR spectroscopy and elemental analysis techniques. Molecular and crystal structures of 2a, 2d, 2e, 2f and 2g were obtained with single-crystal X-ray diffraction studies. These novel NHC precursor's derivatives effectively inhibited the α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Inhibition constant (Ki) were found in the range of 0.30-9.22 nM for α-glycosidase, 13.90-41.46 nM for hCA I, 12.82-49.95 nM for hCA II, 145.82-882.01 nM for BChE, and 280.92-1370.01 nM for AChE, respectively.

Design and synthesis of 2-nitroimidazoles with variable alkylating and acylating functionality.

PubMed

Winters, Thomas; Sercel, Anthony; Suto, Carla; Elliott, William; Leopold, Wilbur; Leopold, Judith; Showalter, Hollis

2014-01-01

The synthesis of a small series of 2-nitroimidazoles in which the β-amino alcohol side chain was amidated with a range of alkylating/acylating functionality is described. Synthetic methodologies were developed that generally provided for selective N-acyl versus N,O-bisacyl products. In vitro, target analogs showed minimal radiosensitization activity, with only a few exhibiting a sensitizer enhancement ratio (SER) >2.0 and C(1.6) values comparable to reference agents RB-6145 and RSU-1069. In an assay to determine potential to alkylate biomolecules, representative analogs showed <1% of the alkylating activity of RSU-1069. In vivo, one analog showed an enhancement ratio of 1.6 relative to vehicle control when tested in B6C3F1 mice with an implanted KHT sarcoma. The data reinforce prior findings that there is a correlation between alkylation potential and in vivo activity.

Photo-induced oxidant-free oxidative C-H/N-H cross-coupling between arenes and azoles

NASA Astrophysics Data System (ADS)

Niu, Linbin; Yi, Hong; Wang, Shengchun; Liu, Tianyi; Liu, Jiamei; Lei, Aiwen

2017-02-01

Direct cross-coupling between simple arenes and heterocyclic amines under mild conditions is undoubtedly important for C-N bonds construction. Selective C(sp2)-H amination is more valuable. Herein we show a selective C(sp2)-H amination of arenes (alkyl-substituted benzenes, biphenyl and anisole derivatives) accompanied by hydrogen evolution by using heterocyclic azoles as nitrogen sources. The reaction is selective for C(sp2)-H bonds, providing a mild route to N-arylazoles. The KIE (kinetic isotope effect) experiment reveals the cleavage of C-H bond is not involved in the rate-determining step. Kinetic studies indicate the first-order behaviour with respect to the arene component. It is interesting that this system works without the need for any sacrificial oxidant and is highly selective for C(sp2)-H activation, whereas C(sp3)-H bonds are unaffected. This study may have significant implications for the functionalization of methylarenes which are sensitive to oxidative conditions.

Comparing Medline citations using modified N-grams

PubMed Central

Nawab, Rao Muhammad Adeel; Stevenson, Mark; Clough, Paul

2014-01-01

Objective We aim to identify duplicate pairs of Medline citations, particularly when the documents are not identical but contain similar information. Materials and methods Duplicate pairs of citations are identified by comparing word n-grams in pairs of documents. N-grams are modified using two approaches which take account of the fact that the document may have been altered. These are: (1) deletion, an item in the n-gram is removed; and (2) substitution, an item in the n-gram is substituted with a similar term obtained from the Unified Medical Language System  Metathesaurus. N-grams are also weighted using a score derived from a language model. Evaluation is carried out using a set of 520 Medline citation pairs, including a set of 260 manually verified duplicate pairs obtained from the Deja Vu database. Results The approach accurately detects duplicate Medline document pairs with an F1 measure score of 0.99. Allowing for word deletions and substitution improves performance. The best results are obtained by combining scores for n-grams of length 1–5 words. Discussion Results show that the detection of duplicate Medline citations can be improved by modifying n-grams and that high performance can also be obtained using only unigrams (F1=0.959), particularly when allowing for substitutions of alternative phrases. PMID:23715801

Substituent effects on rates and torquoselectivities of electrocyclic ring-openings of N-substituted 2-azetines.

PubMed

Lopez, Steven A; Houk, K N

2014-07-03

Transition structures for the conrotatory electrocyclic ring-opening reactions of N-substituted 2-azetines were computed with the density functional M06-2X/6-31+G(d,p). A wide range of substituents from π acceptors (e.g., CHO, CN) to π donors (NMe2, OMe) was explored. Acceptor substituents delocalize the nitrogen lone pair and stabilize the reactant state of 2-azetines, while donors destabilize the 2-azetine reactant state. The conrotatory ring-opening is torquoselective, and the transition state for the outward rotation of the N-substituent and inward rotation of the nitrogen lone pair is preferred. This transition structure is stabilized by an interaction between the nitrogen lone pair and the vacant π* orbital. The activation free energies are linearly related to the reaction free energies and the Taft σR(0) parameter.

Thermodynamic characterization of the interaction behavior of a hydrophobically modified polyelectrolyte and oppositely charged surfactants in aqueous solution: effect of surfactant alkyl chain length.

PubMed

Bai, Guangyue; Nichifor, Marieta; Lopes, António; Bastos, Margarida

2005-01-13

We have used a precision isothermal titration microcalorimeter (ITC) to measure the enthalpy curves for the interaction of a hydrophobically modified polyelectrolyte (D40OCT30) with oppositely charged surfactants (SC(n)S) in aqueous solution. D40OCT30 is a newly synthesized polymer based on dextran having pendant N-(2-hydroxypropyl)-N,N-dimethyl-N-octylammonium chloride groups randomly distributed along the polymer backbone with degree of substitution of 28.1%. The employed anionic surfactants are sodium octyl sulfate (SC(8)S) and sodium tetradecyl sulfate (SC(14)S). Microcalorimetric results along with turbidity and kinematic viscosity measurements demonstrate systematically the thermodynamic characterization of the interaction of D40OCT30/SC(n)S. A three-dimensional diagram with the derived phase boundaries is drawn to describe the effect of the alkyl chain length of surfactant and of the ratio between surfactant and pendant groups on the interaction. A more complete picture of the interaction mechanism for D40OCT30/SC(n)S systems is proposed here.

Influence of alkyl chain length compatibility on microemulsion structure and solubilization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bansal, V.K.; O'Connell, J.P.; Shah, D.O.

1980-06-01

The water solubilization capacity of water/oil microemulsions is studied as a function of alkyl chain length of oil (C/sub 8/ to C/sub 16/), surfactant (C/sub 14/ and C/sub 18/ fatty acid soaps), and alcohol (C/sub 4/ to C/sub 7/). Sodium stearate and sodium myristate were used as surfactants. For n-butanol microemulsions the maximum amount of water solubilized in the microemulsion decreased continuously with increasing oil chain length; for n-heptanol it increased continuously. For n-pentanol and n-hexanol systems, water solubilization reached a maximum when the oil chain length plus alcohol chain length was equal to that of the surfactant. The electricmore » resistance and dielectric constant of the microemulsions also are measured as a function of alkyl chain length of the oil. 48 references.« less

40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

Code of Federal Regulations, 2010 CFR

2010-07-01

... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo...

40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

Code of Federal Regulations, 2011 CFR

2011-07-01

... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo...

Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents.

PubMed

Yang, Jir-Jei; Yin, Jiu-Haw; Yang, Ding-I

2007-05-11

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) kills tumor cells via multiple actions including alkylation and carbamoylation. Previously, we have reported that formation of S-nitrosoglutathione (GSNO) in glioma cells overexpressing inducible nitric oxide synthase (iNOS) contributed to nitric oxide (NO)-dependent carbamoylating chemoresistance against BCNU. To further characterize the effects of NO on alkylating cytotoxicity, colony formation assay was applied to evaluate the effects of various NO donors on rat C6 glioma cells challenged with alkylating agents. We demonstrate that NO donors including GSNO, diethylamine NONOate (DEA/NO), and sodium nitroprusside (SNP) substantially reduced the extent of colony formation in glioma cells treated with alkylating agents, namely methyl methanesulfonate (MMS), N-methyl-N-nitrosourea (MNU), and N-ethyl-N-nitrosourea (ENU). Without alkylating agents these NO-releasing agents alone had no effects on clongenic potential of rat C6 glioma cells. Among these three NO donors used, the effectiveness in potentiating alkylating cytotoxicity is in the order of "GSNO>DEA/NO>SNP" when applied at the same dosages. GSNO also exerted similar synergistic actions reducing the extents of colony formation when co-administrated with 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-hydrazine (compound #1), another alkylating agent that mimics the chloroethylating action of BCNU. Together with our previous findings, we propose that NO donors may be used as adjunct chemotherapy with alkylating agents for such malignant brain tumors as glioblastoma multiforme (GBM). In contrast, production of NO as a result of iNOS induction, such as that occurring after surgical resection of brain tumors, may compromise the efficacy of carbamoylating chemotherapy.

Synthesis of alkyl-substituted six-membered lactones through ring-closing metathesis of homoallyl acrylates. An easy route to pyran-2-ones, constituents of tobacco flavor.

PubMed

D'Annibale, Andrea; Ciaralli, Laura; Bassetti, Mauro; Pasquini, Chiara

2007-08-03

The ring-closing metathesis (RCM) reactions of homoallylic acrylates bearing alkyl substituents on various positions of their skeleton afford the corresponding pentenolides in the presence of carbene ruthenium catalysts. For R3 = R4 = H, or R3 = Me, R4 = H, the reactions are catalyzed by complex [RuCl2(PCy3)2(=CHPh)], while a second-generation Grubbs catalyst is required when R3 = H and R4 = Me, R3 = R4 = Me, or R3 = i-Pr and R4 = H. Alkyl substitution at the homoallylic carbon (R1, R2) increases the yield of the reaction when both the acrylic and/or homoallylic double bonds are methyl-substituted. The interaction of the catalyst with the substrate in the initiation stage involves the homoallylic double bond rather than the acrylic moiety, and the resulting alkylidene species from the first-generation Grubbs catalyst can be observed by 1H and 31P NMR. The racemic tobacco constituents 4-isopropyl-5,6-dihydropyran-2-one and 4-isopropyltetrahydropyran-2-one are prepared via a short reaction sequence, involving the RCM reaction as the key transformation.

From N-triisopropylsilylpyrrole to an optically active C-4 substituted pyroglutamic acid: total synthesis of penmacric acid.

PubMed

Berini, Christophe; Pelloux-Léon, Nadia; Minassian, Frédéric; Denis, Jean-Noël

2009-11-07

The stereoselective synthesis of penmacric acid, an optically active C-4 substituted pyroglutamic acid, has been efficiently achieved through an unusual 11-step sequence starting from simple N-triisopropylsilylpyrrole. The key-steps are the initial addition of the pyrrole nucleus onto a chiral nitrone and the obtention of the pyroglutamic acid moiety by reductive hydrogenation of the pyrrole followed by oxidation of the corresponding pyrrolidine into pyrrolidinone.

Boron doped GaN and InN: Potential candidates for spintronics

NASA Astrophysics Data System (ADS)

Fan, S. W.; Huang, X. N.; Yao, K. L.

2017-02-01

The full potential linearized augmented plane wave method together with the Tran-Blaha modified Becke-Johnson potential is utilized to investigate the electronic structures and magnetism for boron doped GaN and InN. Calculations show the boron substituting nitrogen (BN defects) could induce the GaN and InN to be half-metallic ferromagnets. The magnetic moments mainly come from the BN defects, and each BN defect would produce the 2.00 μB total magnetic moment. The electronic structures indicate the carriers-mediated double exchange interaction plays a crucial role in forming the ferromagnetism. Positive chemical pair interactions imply the BN defects would form the homogeneous distribution in GaN and InN matrix. Moderate formation energies suggest that GaN and InN with BN defects could be fabricated experimentally.

Multiple adaptive amino acid substitutions increase the virulence of a wild waterfowl-origin reassortant H5N8 avian influenza virus in mice.

PubMed

Yu, Zhijun; Cheng, Kaihui; Sun, Weiyang; Zhang, Xinghai; Xia, Xianzhu; Gao, Yuwei

2018-01-15

A novel H5N8 highly pathogenic avian influenza virus (HPAIV) caused poultry outbreaks in the Republic of Korea in 2014. The novel H5N8 HPAIV has spread to Asia, Europe, and North America and caused great public concern from then on. Here, we generated mouse-adapted variants of a wild waterfowl-origin H5N8 HPAIV to identify adaptive mutants that confer enhanced pathogenicity in mammals. The mouse lethal doses (MLD 50 ) of the mouse-adapted variants were reduced 31623-fold compared to the wild-type (WT) virus. Mouse-adapted variants displayed enhanced replication in vitro and in vivo, and expanded tissue tropism in mice. Sequence analysis revealed four amino acid substitutions in the PB2 (E627K), PA (F35S), HA (R227H), and NA (I462V) proteins. These data suggest that multiple amino acid substitutions collaboratively increase the virulence of a wild bird-origin reassortant H5N8 HPAIV and cause severe disease in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

No-carrier-added [.sup.18 F]-N-fluoroalkylspiroperidols

DOEpatents

Shiue, Chyng-Yann; Wolf, Alfred P.; Bai, Lan-Qin; Teng, Ren-Tui

1989-01-01

There is disclosed radioligands labeled with the position emitting radionuclide [.sup.18 F] suitable for dynamic study in living humans with position emission transaxial tomography. These new [.sup.18 F]-N-fluoroalkylspiroperidols, wherein the alkyl group contains from 2-6 carbon atoms, exhibit extremely high affinity for the dopamine receptors and provide enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to make these new radioligands useful for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for these radioligands as well as a new procedure for preparing the radiolabeled alkyl halide alkylating reagents are also disclosed.

One-Pot Synthesis of N-Substituted β-Amino Alcohols from Aldehydes and Isocyanides.

PubMed

Cioc, Răzvan C; van der Niet, Daan J H; Janssen, Elwin; Ruijter, Eelco; Orru, Romano V A

2015-05-18

A practical two-stage one-pot synthesis of N-substituted β-amino alcohols using aldehydes and isocyanides as starting materials has been developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon-carbon bond disconnection, this protocol complements traditional approaches that involve amines and various carbon electrophiles (epoxides, α-halo ketones, β-halohydrins). Medicinally relevant products can be prepared in a concise and efficient way from simple building blocks, as demonstrated in the synthesis of the antiasthma drug salbutamol. Upgrading the synthesis to an enantioselective variant is also feasible. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Theoretical Study of the Mechanism of the Alkylation of Guanine by N- Nitroso Compounds.

DTIC Science & Technology

1992-01-01

Later, Loveless isolated an 0 6 - methylated product from treatment with MNU and was the first to suggest a relevance of O6 alkylation 11 to the...replication. The ultimate metabolite involved in the alkylation reaction has generally been thought to be an alkyldiazonium ion or, its decomposition... Methylation of Formamide by the Methyldiazonium Ion .................... 60 Table 3.10: Intrinsic Barriers for Degenerate SN 2 Reactions .......... 66 Table

Processable Electronically Conducting Polymers

DTIC Science & Technology

1991-01-01

polyheterocycles and will be discussed in detail later. The Grignard coupling reaction of alkyl substituted 1,4- dibromobenzenes was initially employed, as...R 2 ,R 3 ) along with alkyl , aryl, benzyl, and -CH 2 CN substituents on the nitrogen (R I ). Since aniline preferentially oxidatively polymerizes at...but, in the case of N-aryl substituted anilines , an alternative mecha- nism has been proposed [171], which is outlined in Scheme 9. Both poly(N

Microbial biodegradation of aromatic alkanoic naphthenic acids is affected by the degree of alkyl side chain branching

PubMed Central

Johnson, Richard J; Smith, Ben E; Sutton, Paul A; McGenity, Terry J; Rowland, Steven J; Whitby, Corinne

2011-01-01

Naphthenic acids (NAs) occur naturally in oil sands and enter the environment through natural and anthropogenic processes. NAs comprise toxic carboxylic acids that are difficult to degrade. Information on NA biodegradation mechanisms is limited, and there are no studies on alkyl branched aromatic alkanoic acid biodegradation, despite their contribution to NA toxicity and recalcitrance. Increased alkyl side chain branching has been proposed to explain NA recalcitrance. Using soil enrichments, we examined the biodegradation of four aromatic alkanoic acid isomers that differed in alkyl side chain branching: (4′-n-butylphenyl)-4-butanoic acid (n-BPBA, least branched); (4′-iso-butylphenyl)-4-butanoic acid (iso-BPBA); (4′-sec-butylphenyl)-4-butanoic acid (sec-BPBA) and (4′-tert-butylphenyl)-4-butanoic acid (tert-BPBA, most branched). n-BPBA was completely metabolized within 49 days. Mass spectral analysis confirmed that the more branched isomers iso-, sec- and tert-BPBA were transformed to their butylphenylethanoic acid (BPEA) counterparts at 14 days. The BPEA metabolites were generally less toxic than BPBAs as determined by Microtox assay. n-BPEA was further transformed to a diacid, showing that carboxylation of the alkyl side chain occurred. In each case, biodegradation of the carboxyl side chain proceeded through beta-oxidation, which depended on the degree of alkyl side chain branching, and a BPBA degradation pathway is proposed. Comparison of 16S rRNA gene sequences at days 0 and 49 showed an increase and high abundance at day 49 of Pseudomonas (sec-BPBA), Burkholderia (n-, iso-, tert-BPBA) and Sphingomonas (n-, sec-BPBA). PMID:20962873

Modeling the Conformation-Specific Infrared Spectra of N-Alkylbenzenes

NASA Astrophysics Data System (ADS)

Tabor, Daniel P.; Sibert, Edwin; Hewett, Daniel M.; Korn, Joseph A.; Zwier, Timothy S.

2016-06-01

Conformation-specific UV-IR double resonance spectra are presented for n-alkylbenzenes. With the aid of a local mode Hamiltonian that includes the effects of stretch-bend Fermi coupling, the spectra of ethyl, n-propyl, and n-butylbenzene are assigned to individual conformers. These molecules allow for further development of the work on a first principles method for calculating alkyl stretch spectra. Due to the consistency of the anharmonic couplings from conformer to conformer, construction of the model Hamiltonian for a given conformer only requires a harmonic frequency calculation at the conformer's minimum geometry as an input. The model Hamiltonian can be parameterized with either density functional theory or MP2 electronic structure calculations. The relative strengths and weaknesses of these methods are evaluated, including their predictions of the relative energetics of the conformers. Finally, the IR spectra for conformers that have the alkyl chain bend back and interact with the π cloud of the benzene ring are modeled.

Four new 6-oxy purine alkaloids from the South China Sea sponge, Haliclona cymaeformis

NASA Astrophysics Data System (ADS)

Chen, Min; Wu, Xudong; Shen, Nanxing; Wang, Changyun

2017-12-01

In this study, the chemical analysis of the marine sponge spieces, Haliclona cymaeformis, collected from the South China Sea was carried out, Two pairs of regioisomers of alkyl substitutional 6-oxy purine alkaloids ( 1a/ 1b and 2a/ 2b) were isolated. All of them possess two structural moieties, a 6-oxy purine nucleus and a pentan-2-one or hexan-2-one alkyl chain. Among them, 1a and 2a are the major N-9-substitutional regioisomers, and 1b and 2b are the minor N-7-substitutional regioisomers.

Highly efficient and direct heterocyclization of dipyridyl ketone to N,N-bidentate ligands

NASA Technical Reports Server (NTRS)

Wang, Jie; Dyers, Leon Jr; Mason, Richard Jr; Amoyaw, Prince; Bu, Xiu R.

2005-01-01

[reaction: see text] Reaction of various aromatic aldehydes with 2,2'-dipyridyl ketone and ammonium acetate in hot acetic acid provides ready access to a series of substituted 1-pyridylimidazo[1,5-a]pyridines, a class of ligands possessing an N,N-bidentate feature, in good yields.

Garlic and associated allyl sulfur components inhibit N-methyl-N-nitrosourea induced rat mammary carcinogenesis.

PubMed

Schaffer, E M; Liu, J Z; Green, J; Dangler, C A; Milner, J A

1996-04-19

Our previous studies demonstrated that dietary garlic powder supplementation inhibits N-nitrosamine induced DNA alkylation in liver and mammary tissue. The present studies compared the impact of dietary supplementation with garlic powder or two garlic constituents, water-soluble S-allyl cysteine (SAC) and oil-soluble diallyl disulfide (DADS), on the incidence of mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU). Female Sprague-Dawley rats were fed semi-purified casein based diets with or without supplements of garlic powder(20g/kg), SAC (57 micromol/kg) or DADS (57 micromol/kg) for 2 weeks prior to treatment with MNU (15 mg/kg body wt). Garlic powder, SAC and DADS supplementation significantly delayed the onset of mammary tumors compared to rats receiving the unsupplemented diet. Tumor incidence 23 weeks after MNU treatment was reduced by 76, 41 and 53% in rats fed garlic, SAC and DADS, respectively, compared to controls (P<0.05). Total tumor number was reduced 81, 35 and 65% by these supplements, respectively (P<0.05). In a separate study the quantity of mammary DNA alkylation occurring 3 h after MNU treatment was reduced in rats fed garlic, SAC or DADS (P<0.05). Specifically, O(6)-methylguanine adducts were reduced by 27, 18 and 23% in rats fed supplemental garlic, SAC and DADS, respectively, compared to controls. N(7)-Methylguanine adducts decreased by 48, 22 and 21% respectively, compared to rats fed the control diet. These studies demonstrate that garlic and associated allyl sulfur components, SAC and DADS, are effective inhibitors of MNU-induced mammary carcinogenesis.

Binding of alkylphenols and alkylated non-phenolics to rainbow trout (Oncorhynchus mykiss) hepatic estrogen receptors.

PubMed

Tollefsen, Knut-Erik; Julie Nilsen, Anja

2008-02-01

Alkylphenols are well-known endocrine disrupters, mediating effects through the estrogen receptor (ER). In the present work, the interaction of alkylphenols and alkylated non-phenolics with hepatic rainbow trout (Oncorhynchus mykiss) estrogen receptors (rtERs) was determined. The role of alkyl chain length and branching, substituent position, number of alkylated groups, and the requirement of a phenolic ring structure was assessed. The results showed that the rtERs bound most alkylphenols, although with 20,000 to 2 million times lower affinity than the endogenous estrogen 17beta-estradiol. Mono-substituted alkylphenols with moderate (C4-C6) and long (C8 and C12) alkyl chain length in the para position exhibited the highest affinity for the rtERs. Substitution with multiple alkyl groups, presence of substituents in the ortho- and meta-position, and lack of a hydroxyl group on the benzene ring reduced the binding affinity. The rtERs resembled the reported binding specificity of the human ER for alkylphenols, although some exceptions were identified.

Ada response – a strategy for repair of alkylated DNA in bacteria

PubMed Central

Mielecki, Damian; Grzesiuk, Elżbieta

2014-01-01

Alkylating agents are widespread in the environment and also occur endogenously. They can be cytotoxic or mutagenic to the cells introducing alkylated bases to DNA or RNA. All organisms have evolved multiple DNA repair mechanisms to counteract the effects of DNA alkylation: the most cytotoxic lesion, N3-methyladenine (3meA), is excised by AlkA glycosylase initiating base excision repair (BER); toxic N1-methyladenine (1meA) and N3-methylcytosine (3meC), induced in DNA and RNA, are removed by AlkB dioxygenase; and mutagenic and cytotoxic O6-methylguanine (O6meG) is repaired by Ada methyltransferase. In Escherichia coli, Ada response involves the expression of four genes, ada, alkA, alkB, and aidB, encoding respective proteins Ada, AlkA, AlkB, and AidB. The Ada response is conserved among many bacterial species; however, it can be organized differently, with diverse substrate specificity of the particular proteins. Here, an overview of the organization of the Ada regulon and function of individual proteins is presented. We put special effort into the characterization of AlkB dioxygenases, their substrate specificity, and function in the repair of alkylation lesions in DNA/RNA. PMID:24810496

A detachable ester bond enables perfect Z-alkylations of olefins for the synthesis of tri- and tetrasubstituted alkenes.

PubMed

Nishikata, Takashi; Nakamura, Kimiaki; Inoue, Yuki; Ishikawa, Shingo

2015-06-25

2-Vinyl-substituted phenol and an alpha-bromoester undergo a tandem esterification-alkylation reaction in the presence of a Cu-amine catalyst system to produce benzene-fused lactone. Z-Alkylated styrene is obtained after hydrolysis of the lactone with perfect selectivity. The simple protocol developed in this work opens a new avenue in the multi-substitution chemistry of alkenes.

Photoaddition of N-substituted piperazines to C60: an efficient approach to the synthesis of water-soluble fullerene derivatives.

PubMed

Troshina, Olesya A; Troshin, Pavel A; Peregudov, Alexander S; Kozlovski, Viacheslav I; Lyubovskaya, Rimma N

2006-07-17

An oxidative radical photoaddition of mono N-substituted piperazines to [60]fullerene was systematically investigated. Reactions of C60 with piperazines bearing bulky electron-withdrawing groups (2-pyridyl, 2-pyrimidinyl) were found to be the most selective and yielded C60(amine)4O as major products along with small amounts of C60(amine)2. In contrast, interactions of fullerene with N-methylpiperazine and N-(tert-butoxycarbonyl)piperazine were found to have low selectivity due to different side reactions. Tetraaminofullerene derivative C60(N-(2-pyridyl)piperazine)4O was found to react readily with organic and inorganic acids to yield highly water-soluble salts (solubility approximately 150 mg mL(-1)). In contrast, C60(N-(2-pyrimidinyl)piperazine)4O undergoes hydrolysis under the same conditions and results in a complex mixture of compounds with an average composition of C60(N-(2-pyrimidinyl)piperazine)2(OH)2O. Radical photoaddition of N-(2-pyridyl)piperazine to fullerene derivatives can be used as a facile route for their transformation into water-soluble compounds. Two model fullerene cycloadducts (a methanofullerene and a pyrrolidinofullerene) were easily converted into mixtures of regioisomers of A=C60(N-(2-pyridyl)piperazine)4O (A=cyclic addend) that give highly water-soluble salts under acid treatment.

Modified reaction mechanism of aerated n-dodecane liquid flowing over heated metal tubes

NASA Technical Reports Server (NTRS)

Reddy, K. T.; Cernansky, N. P.; Cohen, R. S.

1988-01-01

The degradation mechanism of the n-dodecane was studied using a modified jet fuel thermal oxidation tester containing a sample withdrawal system as a reaction vessel. The reaction products were identified using gas chromatography and mass spectorometry. The soluble products were found to consist mainly of C5-C10 n-alkanes and 1-alkenes, C7-C10 aldehydes, tetrahydrofuran derivatives, dodecanol and dodecanone isomers, dodecyl hydroperoxide (ROOH) decomposition products, and C24 alkane isomers. The data from the experiments agreed with those of Hazlett et al. (1977). It was found that alkyl peroxide radical reactions dominate in the autooxidation temperature regime (at T not above 300 C); the dominant path is for the alkyl peroxyl radical to react bimolecularly with fuel to yield primarily alkyl hydroperoxides. The alkyl peroxide radical also undergoes self-termination and unimolecular isomerization and decomposition reactions, to yield smaller amounts of C12 alcohol plus ketone products and tetrahydrofuran derivatives, respectively.

The Synthesis of Methyl-Substituted Spirocyclic Piperidine-Azetidine (2,7-Diazaspiro[3.5]nonane) and Spirocyclic Piperidine-Pyrrolidine (2,8-Diazaspiro[4.5]decane) Ring Systems.

PubMed

Smith, Aaron C; Cabral, Shawn; Kung, Daniel W; Rose, Colin R; Southers, James A; García-Irizarry, Carmen N; Damon, David B; Bagley, Scott W; Griffith, David A

2016-05-06

The synthesis of a series of pharmaceutically important N-protected methyl-substituted spirocyclic piperidine-azetidine (2,7-diazaspiro[3.5]nonane) and spirocyclic piperidine-pyrrolidine (2,8-diazaspiro[4.5]decane) ring systems was developed. These motifs contain two differentiated sites (protected secondary amines) to allow for further functionalization via reductive amination, amidation, or other chemistry. The methyl-substituted spiroazetidine ring systems were accessed using nitrile lithiation/alkylation chemistry while the methyl-substituted spiropyrrolidines were synthesized by 1,4-addition reactions with nitroalkanes, followed by reduction and cyclization. These conditions were then scaled for the synthesis of 1-methyl spirocyclic piperidine-pyrrolidine with a classical resolution of the product using a tartaric acid derivative to isolate a single enantiomer.

Ada response - a strategy for repair of alkylated DNA in bacteria.

PubMed

Mielecki, Damian; Grzesiuk, Elżbieta

2014-06-01

Alkylating agents are widespread in the environment and also occur endogenously. They can be cytotoxic or mutagenic to the cells introducing alkylated bases to DNA or RNA. All organisms have evolved multiple DNA repair mechanisms to counteract the effects of DNA alkylation: the most cytotoxic lesion, N(3)-methyladenine (3meA), is excised by AlkA glycosylase initiating base excision repair (BER); toxic N(1)-methyladenine (1meA) and N(3)-methylcytosine (3meC), induced in DNA and RNA, are removed by AlkB dioxygenase; and mutagenic and cytotoxic O(6)-methylguanine (O(6) meG) is repaired by Ada methyltransferase. In Escherichia coli, Ada response involves the expression of four genes, ada, alkA, alkB, and aidB, encoding respective proteins Ada, AlkA, AlkB, and AidB. The Ada response is conserved among many bacterial species; however, it can be organized differently, with diverse substrate specificity of the particular proteins. Here, an overview of the organization of the Ada regulon and function of individual proteins is presented. We put special effort into the characterization of AlkB dioxygenases, their substrate specificity, and function in the repair of alkylation lesions in DNA/RNA. © 2014 The Authors. FEMS Microbiology Letters published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

A New Family of Ionic Liquids 1-amino-3-alkyl-1,2,3-Triazolium Nitrates

NASA Technical Reports Server (NTRS)

Drake, Greg; Kaplan, Greg; Hall, Leslie; Hawkins, Tommy; Larue, Joann

2004-01-01

A new class of ionic liquids based upon 1-amino-3-alkyl-1,2,3-triazolium nitrates (alkyl = methyl, ethyl, n-propyl, 2-propeny1, and n-butyl) have been synthesized and characterized by vibrational spectra, multinuclear NMR, elemental analysis, and DSC studies. A single crystal x-ray study was carried out for 1-amino-3-methyl-1,2,3-triazolium nitrate and the details will be presented.

Thermodynamic and Spectroscopic Studies of Trivalent f -element Complexation with Ethylenediamine- N,N '-di(acetylglycine)- N,N '-diacetic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heathman, Colt R.; Grimes, Travis S.; Zalupski, Peter R.

In this study, the coordination behavior and thermodynamic features of complexation of trivalent lanthanides and americium by ethylenediamine- N,N'-di(acetylglycine)- N,N'-diacetic acid (EDDAG-DA) (bisamide-substituted-EDTA) were investigated by potentiometric and spectroscopic techniques. Acid dissociation constants (K a) and complexation constants (β) of lanthanides (except Pm) were determined by potentiometric analysis. Absorption spectroscopy was used to determine stability constants for the binding of trivalent americium and neodymium by EDDAG-DA under similar conditions. The potentiometry revealed 5 discernible protonation constants and 3 distinct metal–ligand complexes (identified as ML –, MHL, and MH 2L +). Time-resolved fluorescence studies of Eu-(EDDAG-DA) solutions (at varying pH) identifiedmore » a constant inner-sphere hydration number of 3, suggesting that glycine functionalities contained in the amide pendant arms are not involved in metal complexation and are protonated under more acidic conditions. The thermodynamic studies identified that f-element coordination by EDDAG-DA is similar to that observed for ethylenediamine- N,N,N',N'-tetraacetic acid (EDTA). However, coordination via two amidic oxygens of EDDAG-DA lowers its trivalent f-element complex stability by roughly 3 orders of magnitude relative to EDTA.« less

Thermodynamic and Spectroscopic Studies of Trivalent f -element Complexation with Ethylenediamine- N,N '-di(acetylglycine)- N,N '-diacetic Acid

DOE PAGES

Heathman, Colt R.; Grimes, Travis S.; Zalupski, Peter R.

2016-03-21

In this study, the coordination behavior and thermodynamic features of complexation of trivalent lanthanides and americium by ethylenediamine- N,N'-di(acetylglycine)- N,N'-diacetic acid (EDDAG-DA) (bisamide-substituted-EDTA) were investigated by potentiometric and spectroscopic techniques. Acid dissociation constants (K a) and complexation constants (β) of lanthanides (except Pm) were determined by potentiometric analysis. Absorption spectroscopy was used to determine stability constants for the binding of trivalent americium and neodymium by EDDAG-DA under similar conditions. The potentiometry revealed 5 discernible protonation constants and 3 distinct metal–ligand complexes (identified as ML –, MHL, and MH 2L +). Time-resolved fluorescence studies of Eu-(EDDAG-DA) solutions (at varying pH) identifiedmore » a constant inner-sphere hydration number of 3, suggesting that glycine functionalities contained in the amide pendant arms are not involved in metal complexation and are protonated under more acidic conditions. The thermodynamic studies identified that f-element coordination by EDDAG-DA is similar to that observed for ethylenediamine- N,N,N',N'-tetraacetic acid (EDTA). However, coordination via two amidic oxygens of EDDAG-DA lowers its trivalent f-element complex stability by roughly 3 orders of magnitude relative to EDTA.« less

Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length

PubMed Central

Cho, Kyung Ho; Hariharan, Parameswaran; Mortensen, Jonas S.; Du, Yang; Nielsen, Anne K.; Byrne, Bernadette; Kobilka, Brian K.; Loland, Claus J.; Guan, Lan

2017-01-01

Membrane proteins encapsulated by detergent micelles are widely used for structural study. Because of their amphipathic property, detergents have the ability to maintain protein solubility and stability in an aqueous medium. However, conventional detergents have serious limitations in their scope and utility, particularly for eukaryotic membrane proteins and membrane protein complexes. Thus, a number of new agents have been devised; some have made significant contributions to membrane protein structural studies. However, few detergent design principles are available. In this study, we prepared meta and ortho isomers of the previously reported para-substituted xylene-linked maltoside amphiphiles (XMAs), along with alkyl chain-length variation. The isomeric XMAs were assessed with three membrane proteins, and the meta isomer with a C12 alkyl chain was most effective at maintaining solubility/stability of the membrane proteins. We propose that interplay between the hydrophile–lipophile balance (HLB) and alkyl chain length is of central importance for high detergent efficacy. In addition, differences in inter-alkyl-chain distance between the isomers influence the ability of the detergents to stabilise membrane proteins. PMID:27981750

Mechanisms of Exchange Reactions of Primary and Secondary Alkyl Iodides with Elementary Iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bujake, John E.; Pratt, M. W. T.; Noyes, Richard M.

1961-04-01

Several primary and secondary alkyl iodides exchange thermally with I/ sup 131/ in hexachlorobutadiene between 130 and 200 deg . If the solutions are saturated with oxygen at one atmosphere, rates of exchange fit the kinetic expression k/sub b/STARI! STAl/sub 2/!1/2. Degassed solutions always exchange faster than oxygen saturated ones, but methyl, ethyl, and n-propyl iodides show the same kinetics as with oxygen. Exchange rates of degassed isopropyl and neopentyl iodides also show contributions from a k/sub a/STARI! term. Exchange in degassed ethylene dichloride is 3 to 4 times as fast as in degassed hexachlorobutadiene. Activation energies for k/sub b/more » are usually about 27 to 31 kcal/mole. Effects of substitution on alpha carbon are illustrated by the rate sequence methyl < ethyl < i-propyl = sec-butyl. Effects of substitution on beta carbon are illustrated by the rate sequence ethyl < npropyl>> neopentyl. Since the rates of exchange of methyl, ethyl, and i-propyl iodides vary in the opposite direction from the sequence for bimolecular nucleophilic substitution, the explanation proposed suggests that for nucleophilic substitution the effect of added methyl groups on an alpha carbon is a steric hindrance to solvation by solvent dipoles rather than a steric hindrance to the group attacking the carbon atom itself.« less

New Pioglitazone Metabolites and Absence of Opened-Ring Metabolites in New N-Substituted Thiazolidinedione.

PubMed

Campos, Michel Leandro; Cerqueira, Letícia Bonancio; Silva, Bruna Cristina Ulian; Franchin, Taísa Busaranho; Galdino-Pitta, Marina Rocha; Pitta, Ivan Rocha; Peccinini, Rosângela Gonçalves; Pontarolo, Roberto

2018-06-01

Thiazolidinediones (TZDs) are drugs used to treat type 2 diabetes mellitus; however, several safety concerns remain regarding the available drugs in this class. Therefore, the search for new TZD candidates is ongoing; metabolism studies play a crucial step in the development of new candidates. Pioglitazone, one of the most commonly used TZDs, and GQ-11, a new N -substituted TZD, were investigated in terms of their metabolic activity in rat and human liver microsomes to assess their metabolic stability and investigate their metabolites. Methods for preparation of samples were based on liquid-liquid extraction and protein precipitation. Quantitation was performed using liquid chromatography (LC)-tandem mass spectrometry, and the metabolite investigation was performed using ultraperformance LC coupled to a hybrid quadrupole-time of flight mass spectrometer. The predicted intrinsic clearance of GQ-11 was 70.3 and 46.1 ml/kg per minute for rats and humans, respectively. The predicted intrinsic clearance of pioglitazone was 24.1 and 15.9 ml/kg per minute for rats and humans, respectively. The pioglitazone metabolite investigation revealed two unpublished metabolites (M-D and M-A). M-A is a hydration product and may be related to the mechanism of ring opening and the toxicity of pioglitazone. The metabolites of GQ-11 are products of oxidation; no ring-opening metabolite was observed for GQ-11. In conclusion, under the same experimental conditions, a ring-opening metabolite was observed only for pioglitazone. The resistance of GQ-11 to the ring opening is probably related to N -substitution in the TZD ring. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Synthesis of substituted pyrazines

DOEpatents

Pagoria, Philip F.; Zhang, Mao Xi

2016-10-04

A method for synthesizing a pyrazine-containing material according to one embodiment includes contacting an iminodiacetonitrile derivative with a base and a reagent selected from a group consisting of hydroxylamine, a hydroxylamine salt, an aliphatic primary amine, a secondary amine, an aryl-substituted alkylamine a heteroaryl-substituted alkyl amine, an alcohol, an alkanolamine and an aryl alcoholamine. Additional methods and several reaction products are presented. ##STR00001##

Inducible repair of alkylated DNA in microorganisms.

PubMed

Mielecki, Damian; Wrzesiński, Michał; Grzesiuk, Elżbieta

2015-01-01

Alkylating agents, which are widespread in the environment, also occur endogenously as primary and secondary metabolites. Such compounds have intrinsically extremely cytotoxic and frequently mutagenic effects, to which organisms have developed resistance by evolving multiple repair mechanisms to protect cellular DNA. One such defense against alkylation lesions is an inducible Adaptive (Ada) response. In Escherichia coli, the Ada response enhances cell resistance by the biosynthesis of four proteins: Ada, AlkA, AlkB, and AidB. The glycosidic bonds of the most cytotoxic lesion, N3-methyladenine (3meA), together with N3-methylguanine (3meG), O(2)-methylthymine (O(2)-meT), and O(2)-methylcytosine (O(2)-meC), are cleaved by AlkA DNA glycosylase. Lesions such as N1-methyladenine (1meA) and N3-methylcytosine (3meC) are removed from DNA and RNA by AlkB dioxygenase. Cytotoxic and mutagenic O(6)-methylguanine (O(6)meG) is repaired by Ada DNA methyltransferase, which transfers the methyl group onto its own cysteine residue from the methylated oxygen. We review (i) the individual Ada proteins Ada, AlkA, AlkB, AidB, and COG3826, with emphasis on the ubiquitous and versatile AlkB and its prokaryotic and eukaryotic homologs; (ii) the organization of the Ada regulon in several bacterial species; (iii) the mechanisms underlying activation of Ada transcription. In vivo and in silico analysis of various microorganisms shows the widespread existence and versatile organization of Ada regulon genes, including not only ada, alkA, alkB, and aidB but also COG3826, alkD, and other genes whose roles in repair of alkylated DNA remain to be elucidated. This review explores the comparative organization of Ada response and protein functions among bacterial species beyond the classical E. coli model. Copyright © 2014 Elsevier B.V. All rights reserved.

Anti-Helicobacter pylori activities of selected N-substituted cinnamamide derivatives evaluated on reference and clinical bacterial strains.

PubMed

Klesiewicz, Karolina; Karczewska, Elżbieta; Nowak, Paweł; Skiba-Kurek, Iwona; Sito, Edward; Pańczyk, Katarzyna; Koczurkiewicz, Paulina; Żelaszczyk, Dorota; Pękala, Elżbieta; Waszkielewicz, Anna M; Budak, Alicja; Marona, Henryk; Gunia-Krzyżak, Agnieszka

2018-05-01

In this study, thirty-five N-substituted derivatives of cinnamic acid amide (cinnamamide) were evaluated for anti-Helicobacter pylori activity using an agar disc-diffusion method. Qualitative screening was performed on a reference H. pylori strain (ATCC 43504), resulting in the identification of the three most active compounds, 8 (R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide, minimal inhibitory concentration, MIC = 7.5 µg/mL), 23 ((2E)-3-(4-chlorophenyl)-N-(2-hydroxycyclohexyl)prop-2-enamide, MIC = 10 µg/mL), and 28 ((2E)-3-(4-chlorophenyl)-N-(4-oxocyclohexyl)prop-2-enamide, MIC = 10 µg/mL). These compounds were further tested on twelve well-characterized clinical strains, yielding MIC values that ranged from 10 to 1000 µg/mL. Preliminary safety assessments of the compounds were made using the MTT viability test for cytotoxicity and Ames test for mutagenicity, which showed them to be generally safe, although compounds 8 and 28 showed mutagenic activity at some of the tested concentrations. The results of this study showed the anti-H. pylori potential of cinnamamide derivatives.

Stacking fault effects in Mg-doped GaN

NASA Astrophysics Data System (ADS)

Schmidt, T. M.; Miwa, R. H.; Orellana, W.; Chacham, H.

2002-01-01

First-principles total energy calculations are performed to investigate the interaction of a stacking fault with a p-type impurity in both zinc-blende and wurtzite GaN. For both structures we find that, in the presence of a stacking fault, the impurity level is a more localized state in the band gap. In zinc-blende GaN, the minimum energy position of the substitutional Mg atom is at the plane of the stacking fault. In contrast, in wurtzite GaN the substitutional Mg atom at the plane of the stacking fault is a local minimum and the global minimum is the substitutional Mg far from the fault. This behavior can be understood as a packing effect which induces a distinct strain relief process, since the local structure of the stacking fault in zinc-blende GaN is similar to fault-free wurtzite GaN and vice-versa.

NO3- Coordination in Aqueous Solutions by 15N/ 14N and 18O/natO Isotopic Substitution: What Can We Learn from Molecular Simulation?

DOE PAGES

Chialvo, Ariel A.; Vlcek, Lukas

2014-12-16

We explore the deconvolution of the water-nitrate correlations by the first-order difference approach involving neutron diffraction of heavy- and null-aqueous solutions of KNO 3 under 14N 15N and natON 18ON substitutions to achieve a full characterization of the first water coordination around the nitrate ion. For that purpose we performed isobaric-isothermal simulations of 3.5m KNO 3 aqueous solutions at ambient conditions to generate the relevant radial distribution functions (RDF) required in the analysis (a) to identify the individual partial contributions to the total neutron weighted distribution function, (b) to isolate and assess the contribution of NO 3 -!K + pairmore » formation, (c) to test the accuracy of the NDIS-based coordination calculations and XRDbased assumptions, and (d) to describe the water coordination around both the nitrogen and oxygen sites of the nitrate ion.« less

Combined Experimental and Computational Study on the Unimolecular Decomposition of JP-8 Jet Fuel Surrogates. I. n-Decane (n-C10H22).

PubMed

Zhao, Long; Yang, Tao; Kaiser, Ralf I; Troy, Tyler P; Ahmed, Musahid; Belisario-Lara, Daniel; Ribeiro, Joao Marcelo; Mebel, Alexander M

2017-02-16

Exploiting a high temperature chemical reactor, we explored the pyrolysis of helium-seeded n-decane as a surrogate of the n-alkane fraction of Jet Propellant-8 (JP-8) over a temperature range of 1100-1600 K at a pressure of 600 Torr. The nascent products were identified in situ in a supersonic molecular beam via single photon vacuum ultraviolet (VUV) photoionization coupled with a mass spectroscopic analysis of the ions in a reflectron time-of-flight mass spectrometer (ReTOF). Our studies probe, for the first time, the initial reaction products formed in the decomposition of n-decane-including radicals and thermally labile closed-shell species effectively excluding mass growth processes. The present study identified 18 products: molecular hydrogen (H 2 ), C2 to C7 1-alkenes [ethylene (C 2 H 4 ) to 1-heptene (C 7 H 14 )], C1-C3 radicals [methyl (CH 3 ), vinyl (C 2 H 3 ), ethyl (C 2 H 5 ), propargyl (C 3 H 3 ), allyl (C 3 H 5 )], small C1-C3 hydrocarbons [methane (CH 4 ), acetylene (C 2 H 2 ), allene (C 3 H 4 ), methylacetylene (C 3 H 4 )], along with higher-order reaction products [1,3-butadiene (C 4 H 6 ), 2-butene (C 4 H 8 )]. On the basis of electronic structure calculations, n-decane decomposes initially by C-C bond cleavage (excluding the terminal C-C bonds) producing a mixture of alkyl radicals from ethyl to octyl. These alkyl radicals are unstable under the experimental conditions and rapidly dissociate by C-C bond β-scission to split ethylene (C 2 H 4 ) plus a 1-alkyl radical with the number of carbon atoms reduced by two and 1,4-, 1,5-, 1,6-, or 1,7-H shifts followed by C-C β-scission producing alkenes from propene to 1-octene in combination with smaller 1-alkyl radicals. The higher alkenes become increasingly unstable with rising temperature. When the C-C β-scission continues all the way to the propyl radical (C 3 H 7 ), it dissociates producing methyl (CH 3 ) plus ethylene (C 2 H 4 ). Also, at higher temperatures, hydrogen atoms can abstract hydrogen

Catalytic alkylation of remote C-H bonds enabled by proton-coupled electron transfer

NASA Astrophysics Data System (ADS)

Choi, Gilbert J.; Zhu, Qilei; Miller, David C.; Gu, Carol J.; Knowles, Robert R.

2016-11-01

Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process—a subset of the classical Hofmann-Löffler-Freytag reaction—amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Löffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using

Catalytic alkylation of remote C-H bonds enabled by proton-coupled electron transfer.

PubMed

Choi, Gilbert J; Zhu, Qilei; Miller, David C; Gu, Carol J; Knowles, Robert R

2016-11-10

Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process-a subset of the classical Hofmann-Löffler-Freytag reaction-amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Löffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using

Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives

PubMed Central

Sakakibara, Norikazu; Baba, Masanori; Okamoto, Mika; Toyama, Masaaki; Demizu, Yosuke; Misawa, Takashi; Kurihara, Masaaki; Irie, Kohji; Kato, Yoshihisa; Maruyama, Tokumi

2015-01-01

Background A new series of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Methods A series of new 6-azido and 6-amino derivatives of 1-substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicities of the compounds were evaluated using the viability of mock-infected cells. Results Some of these compounds showed good-to-moderate activities against HIV-1 with half maximal effective concentration (EC50) values in the submicromolar or subnanomolar range. Compared with emivirine, compound 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil showed significant anti-HIV-1 activity with an EC50 value of 10 nM and a high selectivity index of 1923. Preliminary structure–activity relationship studies and molecular modeling analyses were carried out to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil; these results may be important for further development of this class of compounds as anti-HIV-1 agents. Conclusion The excellent activity of 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil (EC50: 0.010 ± 0.006 µM, SI: >1923) may serve as the basis for conducting further investigations on the behavior of this class of compounds against drug-resistant mutants. PMID:26149262

DNA Damage Induced by Alkylating Agents and Repair Pathways

PubMed Central

Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

2010-01-01

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

Alkylation effects on the energy transfer of highly vibrationally excited naphthalene.

PubMed

Hsu, Hsu Chen; Tsai, Ming-Tsang; Dyakov, Yuri A; Ni, Chi-Kung

2011-11-04

The energy transfer of highly vibrationally excited isomers of dimethylnaphthalene and 2-ethylnaphthalene in collisions with krypton were investigated using crossed molecular beam/time-of-flight mass spectrometer/time-sliced velocity map ion imaging techniques at a collision energy of approximately 300 cm(-1). Angular-resolved energy-transfer distribution functions were obtained directly from the images of inelastic scattering. The results show that alkyl-substituted naphthalenes transfer more vibrational energy to translational energy than unsubstituted naphthalene. Alkylation enhances the V→T energy transfer in the range -ΔE(d)=-100~-1500 cm(-1) by approximately a factor of 2. However, the maximum values of V→T energy transfer for alkyl-substituted naphthalenes are about 1500~2000 cm(-1), which is similar to that of naphthalene. The lack of rotation-like wide-angle motion of the aromatic ring and no enhancement in very large V→T energy transfer, like supercollisions, indicates that very large V→T energy transfer requires special vibrational motions. This transfer cannot be achieved by the low-frequency vibrational motions of alkyl groups. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DMSO/Tf2O-mediated cross-coupling of tryptamine with substituted aniline to access C3a-N1'-linked pyrroloindoline alkaloids.

PubMed

Tayu, Masanori; Ishizaki, Takako; Higuchi, Kazuhiro; Kawasaki, Tomomi

2015-04-07

The cross-coupling of tryptamine with substituted aniline to access C3a-nitrogen-linked pyrroloindolines has been developed via the consecutive cyclization of tryptamine with DMSO/Tf2O and the substitution of 3a-pyrroloindolylthionium intermediate with aniline. The use of 2,3-dihydrotryptamine instead of aniline enabled easy access to 3a-(1-indolyl)pyrroloindoline and the concise synthesis of C3a-N1'-linked pyrroloindoline alkaloid (±)-psychotriasine was accomplished.

Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands.

PubMed

Harland, Aubrie A; Bender, Aaron M; Griggs, Nicholas W; Gao, Chao; Anand, Jessica P; Pogozheva, Irina D; Traynor, John R; Jutkiewicz, Emily M; Mosberg, Henry I

2016-05-26

N-Acetylation of the tetrahydroquinoline (THQ) core of a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands increases DOR affinity, resulting in ligands with balanced MOR and DOR affinities. We report a series of N-substituted THQ analogues that incorporate various carbonyl-containing moieties to maintain DOR affinity and define the steric and electronic requirements of the binding pocket across the opioid receptors. 4h produced in vivo antinociception (ip) for 1 h at 10 mg/kg.

N-Substituted cis-4a-(3-Hydroxyphenyl)-8a-methyloctahydroisoquinolines Are Opioid Receptor Pure Antagonists

PubMed Central

Carroll, F. Ivy; Chaudhari, Sachin; Thomas, James B.; Mascarella, S. Wayne; Gigstad, Kenneth M.; Deschamps, Jeffrey; Navarro, Hernán A.

2008-01-01

N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a–g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctahydroisoquinolines 6a–g can exist in conformations where the 3-hydroxyphenyl substituent is either axial or equatorial similar to the (3-hydroxyphenyl)piperidines 4. The 3-hydroxyphenyl equatorial conformation is responsible for the antagonist activity observed in the (3-hydroxyphenyl)piperidine antagonists. Single crystal X-ray analysis of 6a shows that the 3-hydroxyphenyl equatorial conformation is favored in the solid state. Molecular modeling studies also suggest that the equatorial conformation has the lower potential energy relative to the axial conformation. Evaluation of compounds 6a–g in the [35S]GTP-γ-S in vitro functional assay showed that they were opioid receptor pure antagonists. N-[4a-(3-Hydroxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinoline-6-yl]-3-(piperidin-1-yl)propionamide (6d) with a Ke of 0.27 nM at the κ opioid receptor with 154- and 46-fold selectively relative to the μ and δ receptors, respectively, possessed the best combination of κ potency and selectivity. PMID:16366600

Acceptor binding energies in GaN and AlN

NASA Astrophysics Data System (ADS)

Mireles, Francisco; Ulloa, Sergio E.

1998-08-01

We employ effective-mass theory for degenerate hole bands to calculate the acceptor binding energies for Be, Mg, Zn, Ca, C, and Si substitutional acceptors in GaN and AlN. The calculations are performed through the 6×6 Rashba-Sheka-Pikus and the Luttinger-Kohn matrix Hamiltonians for wurtzite (WZ) and zinc-blende (ZB) crystal phases, respectively. An analytic representation for the acceptor pseudopotential is used to introduce the specific nature of the impurity atoms. The energy shift due to polaron effects is also considered in this approach. The ionization energy estimates are in very good agreement with those reported experimentally in WZ GaN. The binding energies for ZB GaN acceptors are all predicted to be shallower than the corresponding impurities in the WZ phase. The binding-energy dependence upon the crystal-field splitting in WZ GaN is analyzed. Ionization levels in AlN are found to have similar ``shallow'' values to those in GaN, but with some important differences which depend on the band structure parametrizations, especially the value of the crystal-field splitting used.

Phonon structures of GaN-based random semiconductor alloys

NASA Astrophysics Data System (ADS)

Zhou, Mei; Chen, Xiaobin; Li, Gang; Zheng, Fawei; Zhang, Ping

2017-12-01

Accurate modeling of thermal properties is strikingly important for developing next-generation electronics with high performance. Many thermal properties are closely related to phonon dispersions, such as sound velocity. However, random substituted semiconductor alloys AxB1-x usually lack translational symmetry, and simulation with periodic boundary conditions often requires large supercells, which makes phonon dispersion highly folded and hardly comparable with experimental results. Here, we adopt a large supercell with randomly distributed A and B atoms to investigate substitution effect on the phonon dispersions of semiconductor alloys systematically by using phonon unfolding method [F. Zheng, P. Zhang, Comput. Mater. Sci. 125, 218 (2016)]. The results reveal the extent to which phonon band characteristics in (In,Ga)N and Ga(N,P) are preserved or lost at different compositions and q points. Generally, most characteristics of phonon dispersions can be preserved with indium substitution of gallium in GaN, while substitution of nitrogen with phosphorus strongly perturbs the phonon dispersion of GaN, showing a rapid disintegration of the Bloch characteristics of optical modes and introducing localized impurity modes. In addition, the sound velocities of both (In,Ga)N and Ga(N,P) display a nearly linear behavior as a function of substitution compositions. Supplementary material in the form of one pdf file available from the Journal web page at http://https://doi.org/10.1140/epjb/e2017-80481-0.

pHEMA-nHA encapsulation and delivery of vancomycin and rhBMP-2 enhances its role as a bone graft substitute.

PubMed

Li, Xinning; Xu, Jianwen; Filion, Tera M; Ayers, David C; Song, Jie

2013-08-01

Bone grafts are widely used in orthopaedic procedures. Autografts are limited by donor site morbidity while allografts are known for considerable infection and failure rates. A synthetic composite bone graft substitute poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite (pHEMA-nHA) was previously developed to stably press-fit in and functionally repair critical-sized rat femoral segmental defects when it was preabsorbed with a single low dose of 300 ng recombinant human bone morphogenetic protein-2/7 (rhBMP-2/7). To facilitate clinical translation of pHEMA-nHA as a synthetic structural bone graft substitute, we examined its ability to encapsulate and release rhBMP-2 and the antibiotic vancomycin. We analyzed the compressive behavior and microstructure of pHEMA-nHA as a function of vancomycin incorporation doses using a dynamic mechanical analyzer and a scanning electron microscope. In vitro release of vancomycin was monitored by ultraviolet-visible spectroscopy. Release of rhBMP-2 from pHEMA-nHA-vancomycin was determined by ELISA. Bioactivity of the released vancomycin and rhBMP-2 was examined by bacterial inhibition and osteogenic transdifferentiation capabilities in cell culture, respectively. Up to 4.8 wt% of vancomycin was incorporated into pHEMA-nHA without compromising its structural integrity and compressive modulus. Encapsulated vancomycin was released in a dose-dependent and sustained manner in phosphate-buffered saline over 2 weeks, and the released vancomycin inhibited Escherichia coli culture. The pHEMA-nHA-vancomycin composite released preabsorbed rhBMP-2 in a sustained manner over 8 days and locally induced osteogenic transdifferentiation of C2C12 cells in culture. pHEMA-nHA can encapsulate and deliver vancomycin and rhBMP-2 in a sustained and localized manner with reduced loading doses. The elasticity, osteoconductivity, and rhBMP-2/vancomycin delivery characteristics of pHEMA-nHA may benefit orthopaedic reconstructions or fusions with

Comparison of as-grown and annealed GaN/InGaN : Mg samples

NASA Astrophysics Data System (ADS)

Deng, Qingwen; Wang, Xiaoliang; Xiao, Hongling; Wang, Cuimei; Yin, Haibo; Chen, Hong; Lin, Defeng; Jiang, Lijuan; Feng, Chun; Li, Jinmin; Wang, Zhanguo; Hou, Xun

2011-08-01

Mg-doped InGaN was grown on unintentionally doped GaN layer, and Mg and defect behaviours in both GaN and InGaN : Mg were investigated through photoluminescence measurement at 7 K. Mg acceptor was found in unintentionally doped GaN after thermal annealing in N2 ambient, and Mg activation energy was estimated to be 200 meV and 110 meV for GaN and InGaN, respectively. Particularly, the ultraviolet band (3.0-3.2 eV) in the GaN layer was infrequently observed in the unannealed sample but quenched in the annealed sample; this band may be associated with oxygen-substituted nitrogen defects. Moreover, the measurement errors of photoluminescence and x-ray diffraction originated from strain were taken into account.

Alkylating agent (MNU)-induced mutation in space environment

NASA Astrophysics Data System (ADS)

Ohnishi, T.; Takahashi, A.; Ohnishi, K.; Takahashi, S.; Masukawa, M.; Sekikawa, K.; Amano, T.; Nakano, T.; Nagaoka, S.

2001-01-01

In recent years, some contradictory data about the effects of microgravity on radiation-induced biological responses in space experiments have been reported. We prepared a damaged template DNA produced with an alkylating agent (N-methyl-N-nitroso urea; MNU) to measure incorrect base-incorporation during DNA replication in microgravity. We examined whether mutation frequency is affected by microgravity during DNA replication for a DNA template damaged by an alkylating agent. Using an in vitro enzymatic reaction system, DNA synthesis by Taq polymerase or polymerase III was done during a US space shuttle mission (Discovery, STS-91). After the flight, DNA replication and mutation frequencies were measured. We found that there was almost no effect of microgravity on DNA replication and mutation frequency. It is suggested that microgravity might not affect at the stage of substrate incorporation in induced-mutation frequency.

Copper-catalyzed transformation of ketones to amides via C(CO)-C(alkyl) bond cleavage directed by picolinamide.

PubMed

Ma, Haojie; Zhou, Xiaoqiang; Zhan, Zhenzhen; Wei, Daidong; Shi, Chong; Liu, Xingxing; Huang, Guosheng

2017-09-13

Copper catalyzed chemoselective cleavage of the C(CO)-C(alkyl) bond leading to C-N bond formation with chelation assistance of N-containing directing groups is described. Inexpensive Cu(ii)-acetate serves as a convenient catalyst for this transformation. This method highlights the emerging strategy to transform unactivated alkyl ketones into amides in organic synthesis and provides a new strategy for C-C bond cleavage.

Antimicrobial Peptide Mimicking Primary Amine and Guanidine Containing Methacrylamide Copolymers Prepared by Raft Polymerization

PubMed Central

Exley, Sarah E.; Paslay, Lea C.; Sahukhal, Gyan S.; Abel, Brooks A.; Brown, Tyler D.; McCormick, Charles L.; Heinhorst, Sabine; Koul, Veena; Choudhary, Veena; Elasri, Mohamed O.; Morgan, Sarah E.

2016-01-01

Naturally occurring antimicrobial peptides (AMPs) display the ability to eliminate a wide variety of bacteria, without toxicity to the host eukaryotic cells. Synthetic polymers containing moieties mimicking lysine and arginine components found in AMPs have been reported to show effectiveness against specific bacteria, with the mechanism of activity purported to depend on the nature of the amino acid mimic. In an attempt to incorporate the antimicrobial activity of both amino acids into a single water-soluble copolymer, a series of copolymers containing lysine mimicking aminopropyl methacrylamide (APMA) and arginine mimicking guanadinopropyl methacrylamide (GPMA) were prepared via aqueous RAFT polymerization. Copolymers were prepared with varying ratios of the comonomers, with degree of polymerization of 35–40 and narrow molecular weight distribution to simulate naturally occurring AMPs. Antimicrobial activity was determined against Gram-negative and Gram-positive bacteria under conditions with varying salt concentration. Toxicity to mammalian cells was assessed by hemolysis of red blood cells and MTT assays of MCF-7 cells. Antimicrobial activity was observed for APMA homopolymer and copolymers with low concentrations of GPMA against all bacteria tested, with low toxicity toward mammalian cells. PMID:26558609

The retention and distribution of parent, alkylated, and N/O/S-containing polycyclic aromatic hydrocarbons on the epidermal tissue of mangrove seedlings.

PubMed

Li, Ruilong; Tan, Huadong; Zhu, Yaxian; Zhang, Yong

2017-07-01

The polycyclic aromatic hydrocarbons (PAHs) located on the epidermal tissues showed distinctive toxic effects to root, while the retention and distribution of PAHs on mangrove seedlings poorly understood. Our results confirmed that the partition coefficients (K f ) of the PAHs retained on the epidermal tissue of mangrove roots, such as Kandelia obovata, Avicennia marina and Aegiceras corniculatum, were much higher than the Poaceae plants roots, for example wheat and maize (Wild et al., 2005). Moreover, to the parent and alkyl PAHs, a well negative correlation was observed between the surface polarity of these three species of mangrove root and the K f values (p < 0.05). To the N/O/S containing PAHs, these relationships were not obviously due to existing of the π-π, n-π interactions and hydrogen bonding between the N/O/S-containing PAHs and epidermal tissues. The PAHs retained on these three species of mangrove root epidermal tissues formed larger clusters than that of on Poaceae plants, such as wheat and maize (Wild et al., 2005) due to the limitation of the suberization of the root exodermis and endodermis. After exposure of 30 d, rhizo- and endophytic bacteria degraded parts of the N/O/S-containing PAHs to medium-lifetime fluorescence substances. To our knowledge, this is the first time to assess the retention of PAHs on the epidermal tissue of mangrove root, which will improve our understanding of the root uptake PAHs process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthetic, Infrared, 1Hand 13CNMR Spectral Studies on N-(p-Substituted Phenyl)-p-Substituted Benzenesulphonamides, p-X'C6H4SO2NH- (p-XC6H4), where X' or X = H, CH3, C2H5, F, Cl or Br

NASA Astrophysics Data System (ADS)

Gowda, B. Thimme; Jayalakshmi, K. L.; Shetty, Mahesha

2004-05-01

Thirty N-(p-substituted phenyl)-p-substituted benzenesulphonamides of the general formula, p-X'C6H4SO2NH(p-XC6H4), where X' or X = H, CH3, C2H5, F, Cl or Br, are synthesised and their infrared spectra in the solid state and 1H and 13C NMR spectra in solution are measured. The N-H stretching vibrational frequencies, νN-H vary in the range 3334 - 3219 cm-1, while the asymmetric and symmetric SO2 vibrations appear in the ranges 1377 - 1311 cm-1 and 1182 - 1151 cm-1, respectively. The compounds exhibit S-N and C-N stretching vibrational absorptions in the ranges 937 - 898 cm-1 and 1310 - 1180 cm-1, respectively. There are no particular trends in the variation of these frequencies on substitution with either electron withdrawing or electron donating groups. The 1H and 13C chemical shifts of N-(p-substituted phenyl)-p-substituted benzenesulphonamides, are assigned to various protons and carbons of the two benzene rings. Further, incremental shifts of the ring protons and carbons due to -SO2NH(p-XC6H4) groups in the compounds of the formula, C6H5SO2NH(p-XC6H4), and p-X'C6H4SO2- and p-X'C6H4SO2NH- groups in the compounds of the formula, p-X'C6H4SO2NH(C6H5) are computed and used to calculate the 1H and 13C chemical shifts of the parallely substituted compounds of the general formula p-X'C6H4SO2NH(p-XC6H4). The computed values agree well with the observed chemical shifts. The above incremental shifts are found to correlate with the Hammett substituent parameters.

40 CFR 721.2520 - Alkylated diphenyls.

Code of Federal Regulations, 2010 CFR

2010-07-01

... reporting. (1) The chemical substances identified generically as alkylated diphenyls (PMN Nos. P-90-237, P-90-248, and P-90-249) are subject to reporting under this section for the significant new uses.... Requirements as specified in § 721.90 (a)(4), (b)(4), and (c)(4) (where N = 1 ppb). (ii) [Reserved] (b...

Bi-enhanced N incorporation in GaAsNBi alloys

NASA Astrophysics Data System (ADS)

Occena, J.; Jen, T.; Rizzi, E. E.; Johnson, T. M.; Horwath, J.; Wang, Y. Q.; Goldman, R. S.

2017-06-01

We have examined the influence of bismuth (Bi) and nitrogen (N) fluxes on N and Bi incorporation during molecular-beam epitaxy of GaAs1-x-yNxBiy alloys. The incorporation of Bi is found to be independent of N flux, while the total N incorporation and the fraction of N atoms occupying non-substitutional lattice sites increase with increasing Bi flux. A comparison of channeling nuclear reaction analysis along the [100], [110], and [111] directions with Monte Carlo-Molecular Dynamics simulations indicates that the non-substitutional N primarily incorporate as (N-As)As interstitial complexes. We discuss the influence of Bi adatoms on the formation of arsenic-terminated [110]-oriented step-edges and the resulting enhancement in total N incorporation via the formation of additional (N-As)As.

Pseudomonas aeruginosa cytochrome c551 denaturation by five systematic urea derivatives that differ in the alkyl chain length.

PubMed

Kobayashi, Shinya; Fujii, Sotaro; Koga, Aya; Wakai, Satoshi; Matubayasi, Nobuyuki; Sambongi, Yoshihiro

2017-07-01

Reversible denaturation of Pseudomonas aeruginosa cytochrome c 551 (PAc 551 ) could be followed using five systematic urea derivatives that differ in the alkyl chain length, i.e. urea, N-methylurea (MU), N-ethylurea (EU), N-propylurea (PU), and N-butylurea (BU). The BU concentration was the lowest required for the PAc 551 denaturation, those of PU, EU, MU, and urea being gradually higher. Furthermore, the accessible surface area difference upon PAc 551 denaturation caused by BU was found to be the highest, those by PU, EU, MU, and urea being gradually lower. These findings indicate that urea derivatives with longer alkyl chains are stronger denaturants. In this study, as many as five systematic urea derivatives could be applied for the reversible denaturation of a single protein, PAc 551 , for the first time, and the effects of the alkyl chain length on protein denaturation were systematically verified by means of thermodynamic parameters.

The backbone N-(4-azidobutyl) linker for the preparation of peptide chimera.

PubMed

Fernández-Llamazares, Ana I; García, Jesús; Adan, Jaume; Meunier, David; Mitjans, Francesc; Spengler, Jan; Albericio, Fernando

2013-09-06

A robust synthetic strategy for the introduction of the N-(4-azidobutyl) linker into peptides using standard SPPS techniques is described. Based on the example of Cilengitide it is shown that the N-(4-azidobutyl) group exerts similar conformational restraints as a backbone N-Me group and allows conjugation of a desired molecule either via click chemistry or-after azide reduction-via acylation or reductive alkylation.

Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives.

PubMed

Sakakibara, Norikazu; Baba, Masanori; Okamoto, Mika; Toyama, Masaaki; Demizu, Yosuke; Misawa, Takashi; Kurihara, Masaaki; Irie, Kohji; Kato, Yoshihisa; Maruyama, Tokumi

2015-02-01

A new series of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. A series of new 6-azido and 6-amino derivatives of 1-substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicities of the compounds were evaluated using the viability of mock-infected cells. Some of these compounds showed good-to-moderate activities against HIV-1 with half maximal effective concentration (EC50) values in the submicromolar or subnanomolar range. Compared with emivirine, compound 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil showed significant anti-HIV-1 activity with an EC50 value of 10 nM and a high selectivity index of 1923. Preliminary structure-activity relationship studies and molecular modeling analyses were carried out to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil; these results may be important for further development of this class of compounds as anti-HIV-1 agents. The excellent activity of 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil (EC50: 0.010 ± 0.006 µM, SI: >1923) may serve as the basis for conducting further investigations on the behavior of this class of compounds against drug-resistant mutants. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Pd-Catalyzed regioselective intramolecular dehydrogenative C-5 cross coupling in an N-substituted pyrrole-azole system.

PubMed

Tripathi, Krishna N; Ray, Devalina; Singh, Ravi P

2017-12-06

Functionalized polycyclic pyrrole-azole structures possessing fused six membered and seven membered rings were directly synthesized via ligand-enabled, Pd-catalyzed, site selective, intramolecular cross couplings of N-substituted pyrrole-azoles. C5-H activation in the presence of a reactive C2-H remains a challenge that needs to be addressed and this was targeted to be resolved through the present approach by specifically generating the cyclized products with 83-100% selectivity. The featured methodology provides a novel disconnection for the synthesis of pyrrole containing alkaloids and medicinal compounds.

Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length.

PubMed

Cho, Kyung Ho; Hariharan, Parameswaran; Mortensen, Jonas S; Du, Yang; Nielsen, Anne K; Byrne, Bernadette; Kobilka, Brian K; Loland, Claus J; Guan, Lan; Chae, Pil Seok

2016-12-14

Membrane proteins encapsulated by detergent micelles are widely used for structural study. Because of their amphipathic property, detergents have the ability to maintain protein solubility and stability in an aqueous medium. However, conventional detergents have serious limitations in their scope and utility, particularly for eukaryotic membrane proteins and membrane protein complexes. Thus, a number of new agents have been devised; some have made significant contributions to membrane protein structural studies. However, few detergent design principles are available. In this study, we prepared meta and ortho isomers of the previously reported para-substituted xylene-linked maltoside amphiphiles (XMAs), along with alkyl chain-length variation. The isomeric XMAs were assessed with three membrane proteins, and the meta isomer with a C 12 alkyl chain was most effective at maintaining solubility/stability of the membrane proteins. We propose that interplay between the hydrophile-lipophile balance (HLB) and alkyl chain length is of central importance for high detergent efficacy. In addition, differences in inter-alkyl-chain distance between the isomers influence the ability of the detergents to stabilise membrane proteins. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bi-enhanced N incorporation in GaAsNBi alloys

DOE PAGES

Occena, J.; Jen, T.; Rizzi, E. E.; ...

2017-06-12

We have examined the influence of bismuth (Bi) and nitrogen (N) fluxes on N and Bi incorporation during molecular-beam epitaxy of GaAs 1-x-yN xBi y alloys. The incorporation of Bi is found to be independent of N flux, while the total N incorporation and the fraction of N atoms occupying non-substitutional lattice sites increase with increasing Bi flux. A comparison of channeling nuclear reaction analysis along the [100], [110], and [111] directions with Monte Carlo-Molecular Dynamics simulations indicates that the non-substitutional N primarily incorporate as (N-As) As interstitial complexes. We discuss the influence of Bi adatoms on the formation ofmore » arsenic-terminated [110]-oriented step-edges and the resulting enhancement in total N incorporation via the formation of additional (N-As) As.« less

Carboxy, carboalkoxy and carbamile substituted isonitrile radionuclide complexes

DOEpatents

Jones, Alun G.; Davison, Alan; Kronauge, James; Abrams, Michael J.

1989-01-01

A coordination complex comprising a radionuclide selected from the class consisting of radioactive isotopes of Tc, Ru, Co, Pt and Re and an isonitrile ligand of the formula: (CNX)R, where X is a lower alkyl group having 1 to 4 carbon atoms, wherein R is selected from the group consisting of COOR.sup.1 and CONR.sup.2 R.sup.3 where R.sup.1 can be H, a pharmaceutically acceptable cation, or a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms. R.sup.2, and R.sup.3 can be H, or a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms, and R.sup.2 and R.sup.3 can be the same of different is disclosed. Kits that can be used to form these complexes are also disclosed.

Carboxy, carboalkoxy and carbamile substituted isonitrile radionuclide complexes

DOEpatents

Jones, Alun G.; Davison, Alan; Kronauge, James; Abrams, Michael J.

1988-04-05

A coordination complex comprising a radionuclide selected from the class consisting of radioactive isotopes of Tc, Ru, Co, Pt and Re and an isonitrile ligand of the formula: (CNX)R, where X is a lower alkyl group having 1 to 4 carbon atoms, wherein R is selected from the group consisting of COOR.sup.1 and CONR.sup.2 R.sup.3 where R.sup.1 can be H, a pharmaceutically acceptable cation, or a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms, R.sup.2, and R.sup.3 can be H, or a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms, and R.sup.2 and R.sup.3 can be the same or different is disclosed. Kits that can be used to form these complexes are also disclosed.

Arylation, alkenylation, and alkylation of 2-halopyridine N-oxides with grignard reagents: a solution to the problem of C2/C6 regioselective functionalization of pyridine derivatives.

PubMed

Zhang, Song; Liao, Lian-Yan; Zhang, Fang; Duan, Xin-Fang

2013-03-15

A facile arylation, alkenylation, and alkylation of functionalized 2-halopyridine N-oxides with various Grignard reagents was developed. It represented a highly efficient and selective C-H bond functionalization of pyridine derivatives in the presence of reactive C-Cl or C-Br bonds. Using Cl or Br as a blocking group, C2/C6 site-controllable functionalization of pyridine derivatives has been achieved. Various pyridine compounds can be prepared as illustrated in the total syntheses of Onychine, dielsine, and PARP-1 inhibitor GPI 16539.

4-alkyl-L-(Dehydro)proline biosynthesis in actinobacteria involves N-terminal nucleophile-hydrolase activity of γ-glutamyltranspeptidase homolog for C-C bond cleavage

NASA Astrophysics Data System (ADS)

Zhong, Guannan; Zhao, Qunfei; Zhang, Qinglin; Liu, Wen

2017-07-01

γ-Glutamyltranspeptidases (γ-GTs), ubiquitous in glutathione metabolism for γ-glutamyl transfer/hydrolysis, are N-terminal nucleophile (Ntn)-hydrolase fold proteins that share an autoproteolytic process for self-activation. γ-GT homologues are widely present in Gram-positive actinobacteria where their Ntn-hydrolase activities, however, are not involved in glutathione metabolism. Herein, we demonstrate that the formation of 4-Alkyl-L-(dehydro)proline (ALDP) residues, the non-proteinogenic α-amino acids that serve as vital components of many bioactive metabolites found in actinobacteria, involves unprecedented Ntn-hydrolase activity of γ-GT homologue for C-C bond cleavage. The related enzymes share a key Thr residue, which acts as an internal nucleophile for protein hydrolysis and then as a newly released N-terminal nucleophile for carboxylate side-chain processing likely through the generation of an oxalyl-Thr enzyme intermediate. These findings provide mechanistic insights into the biosynthesis of various ALDP residues/associated natural products, highlight the versatile functions of Ntn-hydrolase fold proteins, and particularly generate interest in thus far less-appreciated γ-GT homologues in actinobacteria.

(Charge separation in photoredox reactions). Informal annual technical progress report, October 1, 1981-October 1, 1982. [N,N,N',N'tetramethylbenzidine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kevan, L.

1982-10-21

During this period work has focused on the structural aspects of photoinduced charge separation in micellar media with initial forays into vesicular media. The primary techniques utilized are electron spin resonance and electron spin echo spectrometry. The analysis of electron spin echo modulation gives a unique handle on very weak hyperfine interactions thus providing a new structural tool for this general problem. Electron spin resonance and electron spin echo studies of the photoionization of N,N,N',N'tetramethylbenzidine (TMB) to give the cation radical have been carried out in anionic, cationic and nonionic micellar solutions frozen to 77/sup 0/K. The photoionization efficiency ofmore » TMB has also been studied in micelles with varying alkyl chain lengths of the surfactant. Stearic acid nitroxide spin probes have also been used to determine some structural aspects of the location of the neutral TMB molecule in anionic micelles before photoionization. The nitroxide work in which the nitroxide is acting as an electron acceptor also shows that a suitable electron acceptor can be located within the micellar structure. The effect of inorganic solutes on the efficiency of the photoionization of TMB in frozen micelles has also been studied. A series of electron scavenger studies have been initiated to study the effect on TMB photoionization efficiency. Electron spin echo detection of laser photogenerated TMB cation in liquid sodium dodecyl sulfate solutions at room temperature has recently been observed.« less

40 CFR 721.10083 - Copper, [29H, 31H-phthalocyaninato (2-)-N29, N30, N31, N32]-, 4-[(17-substituted-3,6,9,12,15...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Copper, [29H, 31H-phthalocyaninato (2... Significant New Uses for Specific Chemical Substances § 721.10083 Copper, [29H, 31H-phthalocyaninato (2-)-N29... substance identified generically as copper, [29H, 31H-phthalocyaninato (2-)-N29, N30, N31, N32]-, 4-[(17...