Studies on separation and purification of fission (99)Mo from neutron activated uranium aluminum alloy.

PubMed

Rao, Ankita; Kumar Sharma, Abhishek; Kumar, Pradeep; Charyulu, M M; Tomar, B S; Ramakumar, K L

2014-07-01

A new method has been developed for separation and purification of fission (99)Mo from neutron activated uranium-aluminum alloy. Alkali dissolution of the irradiated target (100mg) results in aluminum along with (99)Mo and a few fission products passing into solution, while most of the fission products, activation products and uranium remain undissolved. Subsequent purification steps involve precipitation of aluminum as Al(OH)3, iodine as AgI/AgIO3 and molybdenum as Mo-α-benzoin oxime. Ruthenium is separated by volatilization as RuO4 and final purification of (99)Mo was carried out using anion exchange method. The radiochemical yield of fission (99)Mo was found to be >80% and the purity of the product was in conformity with the international pharmacopoeia standards. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ceratocystis larium sp. nov., a new species from Styrax benzoin wounds associated with incense harvesting in Indonesia.

PubMed

van Wyk, M; Wingfield, B D; Clegg, P A; Wingfield, M J

2009-06-01

Styrax benzoin trees, native to the island Sumatra, Indonesia are wounded to produce resin that is collected and burned as incense. These wounds on trees commonly develop into expanding cankers that lead to tree death. The aim of this study was to consider whether Ophiostomatoid fungi, typically associated with wounds on trees might be associated with resin harvesting on S. benzoin. Samples were collected from the edges of artificially induced wounds, and particularly where cankers and staining of the vascular tissue was evident. Tissue samples were incubated in moist chambers and carrot baiting was also used to detect the presence of Ceratocystis spp. Fruiting structures with morphology typical of species in the C. fimbriata s.l. species complex and species in the anamorph genus Thielaviopsis were found, on both the incubated wood and the carrot baits. DNA sequences were generated for the Internal Transcribed Spacer regions 1 and 2 including the 5.8S rRNA gene, part of the beta-tubulin and the Transcription Elongation Factor 1-alpha gene regions. These data were compared with those of other species in the C. fimbriata s.l. species complex and Thielaviopsis using phylogenetic analysis. Morphology of the isolates in culture as well as phylogenetic inference showed that the Thielaviopsis sp. present on the wounds was T. basicola. The Ceratocystis sp. from S. benzoin represents a new taxon in the C. fimbriata s.l. complex described here as C. larium sp. nov.

Propagation of Valuable North Sumatera Benzoin Trees (Styrax Sp) Using Macrocutting Technique

NASA Astrophysics Data System (ADS)

Susilowati, A.; Hartini, K. S.; Rachmat, H. H.; Alvaroby, M.

2017-03-01

Kemenyan known as Sumatran benzoin is North Sumatera local species that produce high valuable rosin and prospective export comodities. However, sustainability of Sumatran benzoin production has many constraints such as instability of resin production, lack information of propagation technique and traditional management system. Until now, comprehensive information for Sumatran benzoin propagation system still not determined yet. The objectives of this research were (1) to get information about propagation technique of Sumatran benzoin and its suitable growing medium and 2) to get information on adventitious root formation in Sumatran benzoin cuttings. Cutting materials (Toba benzoin and Durame benzoin) were originated from 1 year old seedling propagated by seed. Media used were combination of sand : rice husk (1:0 v/v; 1/1 v/v). Results showed that interaction between media and benzoin species significantly affected primer and secondary root lenght. While planting medium significantly improved secondary root length and number. Benzoin species significantly affected primary and secondary root lenght, and secondary root number.

Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons

PubMed Central

Richter, Franziska; Gao, Fuying; Medvedeva, Vera; Lee, Patrick; Bove, Nicholas; Fleming, Sheila M.; Michaud, Magali; Lemesre, Vincent; Patassini, Stefano; De La Rosa, Krystal; Mulligan, Caitlin K.; Sioshansi, Pedrom; Zhu, Chunni; Coppola, Giovanni; Bordet, Thierry; Pruss, Rebecca; Chesselet, Marie-Françoise

2014-01-01

Cholesterol-oximes TRO19622 and TRO40303 target outer mitochondrial membrane proteins and have beneficial effects in preclinical models of neurodegenerative diseases leading to their advancement to clinical trials. Dopaminergic neurons degenerate in Parkinson’s disease (PD) and are prone to oxidative stress and mitochondrial dysfunction. In order to provide insights into the neuroprotective potential of TRO19622 and TRO40303 for dopaminergic neurons in vivo, we assessed their effects on gene expression in laser captured nigrostriatal dopaminergic neurons of wildtype mice and of mice that over-express alpha-synuclein, a protein involved in both familial and sporadic forms of PD (Thy1-aSyn mice). Young mice were fed the drugs in food pellets or a control diet from 1 to 4 months of age, approximately 10 months before the appearance of striatal dopamine loss in this model. Unbiased weighted gene co-expression network analysis (WGCNA) of transcriptional changes revealed effects of cholesterol oximes on transcripts related to mitochondria, cytoprotection and anti-oxidant response in wild-type and transgenic mice, including increased transcription of stress defense (e.g. Prdx1, Prdx2, Glrx2, Hspa9, Pink1, Drp1, Trak1) and dopamine-related (Th, Ddc, Gch1, Dat, Vmat2, Drd2, Chnr6a) genes. Even at this young age transgenic mice showed alterations in transcripts implicated in mitochondrial function and oxidative stress (e.g. Bcl-2, Bax, Casp3, Nos2), and both drugs normalized about 20% of these alterations. Young Thy1-aSyn mice exhibit motor deficits that differ from parkinsonism and are established before the onset of treatment; these deficits were not improved by cholesterol oximes. However, high doses of TRO40303 improved olfaction and produced the same effects as dopamine agonists on a challenging beam test, specifically an increase in footslips, an observation congruent with its effects on transcripts involved in dopamine synthesis. High doses of TRO19622 increased alpha-synuclein aggregates in the substantia nigra; this effect, not seen with TRO40303 was inconsistent and may represent a protective mechanism as in other neurodegenerative diseases. Overall, the results suggest that cholesterol oximes, while not improving early effects of alpha-synuclein overexpression on motor behavior or pathology, may ameliorate the function and resilience of dopaminergic neurons in vivo and support further studies of neuroprotection in models with dopaminergic cell loss. PMID:24844147

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions.

PubMed

Menon, Rajeev S; Biju, Akkattu T; Nair, Vijay

2016-01-01

N-Heterocyclic carbenes (NHCs) have emerged as a powerful class of organocatalysts that mediate a variety of organic transformations. The Benzoin reaction constitutes one of the earliest known carbon-carbon bond-forming reactions catalysed by NHCs. The rapid growth of NHC catalysis in general has resulted in the development of a variety of benzoin and benzoin-type reactions. An overview of such NHC-catalysed benzoin reactions is presented.

Three-Dimensional Photochemical Machining with Lasers

DTIC Science & Technology

1983-11-30

559.91 (1.00) 4-Hydroxybenzophenone 27.78 79.42 359.97 (1.00) 0 19.42 55.52 514.93 (0.78) Benzoin 27.03 77.28 369.96 (1.00) 21.01 60.07 475.96 (0.95...Xanthone I x 104 3 x 103 2 x 10 2 -3 Photosensitizer x = 318-320 nm x 2 340-345 nm Benzoin 310 -- x-Methyl benzoin 200 -- X-Hydroxymethyl benzoin -- 150... Benzoin isopropyl ether -- 230 Benzoin phenyl ether -- 250 (a) From: V. 0. McGinniss, in "Oevelopments in Polymer Photochemistry - 3", N. S. Allen, Ed

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

PubMed Central

Menon, Rajeev S; Biju, Akkattu T

2016-01-01

Summary N-Heterocyclic carbenes (NHCs) have emerged as a powerful class of organocatalysts that mediate a variety of organic transformations. The Benzoin reaction constitutes one of the earliest known carbon–carbon bond-forming reactions catalysed by NHCs. The rapid growth of NHC catalysis in general has resulted in the development of a variety of benzoin and benzoin-type reactions. An overview of such NHC-catalysed benzoin reactions is presented. PMID:27340440

Anticancer and antiviral effects and inactivation of S-adenosyl-L-homocysteine hydrolase with 5'-carboxaldehydes and oximes synthesized from adenosine and sugar-modified analogues.

PubMed

Wnuk, S F; Yuan, C S; Borchardt, R T; Balzarini, J; De Clercq, E; Robins, M J

1997-05-23

Selectively protected adenine nucleosides were converted into 5'-carboxaldehyde analogues by Moffatt oxidation (dimethyl sulfoxide/dicyclohexylcarbodiimide/dichloroacetic acid) or with the Dess-Martin periodinane reagent. Hydrolysis of a 5'-fluoro-5'-S-methyl-5'-thio (alpha-fluoro thioether) arabinosyl derivative also gave the 5'-carboxaldehyde. Treatment of 5'-carboxaldehydes with hydroxylamine [or O-(methyl, ethyl, and benzyl)hydroxylamine] hydrochloride gave E/Z oximes. Treatment of purified oximes with aqueous trifluoroacetic acid and acetone effected trans-oximation to provide clean samples of 5'-carboxaldehydes. Adenosine (Ado)-5'-carboxaldehyde and its 4'-epimer are potent inhibitors of S-adenosyl-L-homocysteine (AdoHcy) hydrolase. They bind efficiently to the enzyme and undergo oxidation at C3' to give 3'-keto analogues with concomitant reduction of the NAD+ cofactor to give an inactive, tightly bound NADH-enzyme complex (type I cofactor-depletion inhibition). Potent type I inhibition was observed with 5'-carboxaldehydes that contain a ribo cis-2',3'-glycol. Their oxime derivatives are "proinhibitors" that undergo enzyme-catalyzed hydrolysis to release the inhibitors at the active site. The 2'-deoxy and 2'-epimeric (arabinosyl) analogues were much weaker inhibitors, and the 3'-deoxy compounds bind very weakly. Ado-5'-carboxaldehyde oxime had potent cytotoxicity in tumor cell lines and was toxic to normal human cells. Analogues had weaker cytotoxic and antiviral potencies, and the 3'-deoxy compounds were essentially devoid of cytotoxic and antiviral activity.

Microfluidic etching and oxime-based tailoring of biodegradable polyketoesters.

PubMed

Barrett, Devin G; Lamb, Brian M; Yousaf, Muhammad N

2008-09-02

A straightforward, flexible, and inexpensive method to etch biodegradable poly(1,2,6-hexanetriol alpha-ketoglutarate) films is reported. Microfluidic delivery of the etchant, a solution of NaOH, can create micron-scale channels through local hydrolysis of the polyester film. In addition, the presence of a ketone in the repeat unit allows for prior or post chemoselective modifications, enabling the design of functionalized microchannels. Delivery of oxyamine tethered ligands react with ketone groups on the polyketoester to generate covalent oxime linkages. By thermally sealing an etched film to a second flat surface, poly(1,2,6-hexanetriol alpha-ketoglutarate) can be used to create biodegradable microfluidic devices. In order to determine the versatility of the microfluidic etch technique, poly(epsilon-caprolactone) was etched with acetone. This strategy provides a facile method for the direct patterning of biodegradable materials, both through etching and chemoselective ligand immobilization.

Dynamic Kinetic Resolution Enabled by Intramolecular Benzoin Reaction: Synthetic Applications and Mechanistic Insights.

PubMed

Zhang, Guoxiang; Yang, Shuang; Zhang, Xiaoyan; Lin, Qiqiao; Das, Deb K; Liu, Jian; Fang, Xinqiang

2016-06-29

The highly enantio-, diastereo-, and regioselective dynamic kinetic resolution of β-ketoesters and 1,3-diketones was achieved via a chiral N-heterocyclic carbene catalyzed intramolecular cross-benzoin reaction. A variety of tetralone derivatives bearing two contiguous stereocenters and multiple functionalities were liberated in moderate to excellent yields and with high levels of stereoselectivity (>95% ee and >20:1 dr in most cases). In addition, the excellent regioselectivity control for aryl/alkyl 1,3-diketones, and the superior electronic differentiation of 1,3-diarylketones were highlighted. Moreover, a set of new mechanistic rationale that differs with the currently widely accepted understanding of intramolecular benzoin reactions was established to demonstrate the superior preference of benzoin over aldol transformation: (1) A coexistence of competitive aldol and benzoin reactions was detected, but a retro-aldol-irreversible benzoin process performs a vital role in the generation of predominant benzoin products. (2) The most essential role of an N-electron-withdrawing substituent in triazolium catalysts was revealed to be accelerating the rate of the benzoin transformation, rather than suppressing the aldol process through reducing the inherent basicity of the catalyst.

Using NMR Spectroscopy to Probe the Chemo- and Diastereoselectivity in the NaBH[subscript 4] Reduction of Benzoin Acetate and Benzoin Benzoate

ERIC Educational Resources Information Center

Saba, Shahrokh; Cagino, Kristen; Bennett, Caitlin

2015-01-01

A pedagogically useful discovery-based undergraduate organic chemistry lab experiment probing the chemo- and diastereoselectivity in the NaBH[subscript 4] reduction of two chiral ketoesters (benzoin acetate and benzoin benzoate) has been developed. This experiment complements a previously described and highly popular discovery-based experiment…

Infrared spectroscopy and molecular simulations of a polymeric sorbent and its enantioselective interactions with benzoin enantiomers.

PubMed

Tsui, Hung-Wei; Willing, Jonathan N; Kasat, Rahul B; Wang, Nien-Hwa Linda; Franses, Elias I

2011-11-10

Retention factors, k(R) and k(S), and enantioselectivities, S ≡ k(R)/k(S), of amylose tris[(S)-α-methylbenzylcarbamate] (AS) sorbent for benzoin (B) enantiomers were measured for various isopropyl alcohol (IPA)/n-hexane compositions of the high-performance liquid chromatography (HPLC) mobile phase. Novel data for pure n-hexane show that k(R) = 106, k(S) = 49.6, and S = 2.13. With some IPA from 0.5 to 10 vol %, with S = 1.8-1.4, the retention factors were smaller. Infrared spectra showed evidence of substantial hydrogen bonding (H-bonding) interactions in the pure polymer phase and additional H-bonding interactions between AS and benzoin. Density functional theory (DFT) was used to model the chain-chain and chain-benzoin H-bonding and other interactions. DFT was also used to predict fairly well the IR wavenumber shifts caused by the H-bonds. DFT simulations of IR bands of NH and C═O allowed for the first time the predictions of relative intensities and relative populations of H-bonding strengths. Molecular dynamics (MD) simulations were used to model a single 12-mer polymer chain. MD simulations predicted the existence of various potentially enantioselective cavities, two of which are sufficiently large to accommodate a benzoin molecule. Then "docking" studies of benzoin in AS with MD, Monte Carlo (MC), and MC/MD simulations were done to probe the AS-B interactions. The observed enantioselectivities are predicted to be primarily due to two H-bonds, of the kind AS CO···HO (R)-benzoin and AS NH···OC (R)-benzoin, and two π-π (phenyl-phenyl) interactions for (R)-benzoin and one H-bond, of type AS CO···HO (S)-benzoin, and one π-π interaction for (S)-benzoin. The MC/MD predictions are consistent with the HPLC and IR results.

Direct evidence of photochemical α-cleavage of benzoin in fluid solutions

NASA Astrophysics Data System (ADS)

Koyanagi, Motohiko; Futami, Hiroshi; Mukai, Masahiro; Yamauchi, Seigo

1989-02-01

By means of optical absorption, 1 NMR, and transient EPR techniques, the fate of diluted benzoin upon light irradiation to its S 1 (nπ*) state has been investigated in methylcyclohexane and benzene solutions at room temperature. The CIDEP spectrum of benzoin is observed for the first time, and the intermediate radicals involved are assigned. The overall results show that the main scheme of the photochemical reactions is the α-cleavage occurring in the excited triplet state of benzoin, as proved in the almost net emission pattern of the CIDEP spectra. A stoichiometric reaction leading to effective benzaldehyde formation is established for the benzoin solutions.

Mechanism and scope of the cyanide-catalyzed cross silyl benzoin reaction.

PubMed

Linghu, Xin; Bausch, Cory C; Johnson, Jeffrey S

2005-02-16

In this work, cross silyl benzoin addition reactions between acylsilanes (1) and aldehydes (2) catalyzed by metal cyanides are described. Unsymmetrical aryl-, heteroaryl-, and alkyl-substituted benzoin adducts can be generated in moderate to excellent yields with complete regiocontrol using potassium cyanide and a phase transfer catalyst. From a screen of transition metal cyanide complexes, lanthanum tricyanide was identified as an improved second-generation catalyst for the cross silyl benzoin reaction. A study of the influence of water on the KCN-catalyzed cross silyl benzoin addition revealed more practical reaction conditions using unpurified solvent under ambient conditions. A sequential silyl benzoin addition/cyanation/O-acylation reaction that resulted in two new C-C bonds was achieved in excellent yield. The mechanism of cross silyl benzoin addition is proposed in detail and is supported by crossover studies and a number of unambiguous experiments designed to ascertain the reversibility of key steps. No productive chemistry arises from cyanation of the more electrophilic aldehyde component. Formation of the carbon-carbon bond is shown to be the last irreversible step in the reaction.

Improving the rhinomanometry technique using benzoin tincture.

PubMed

Arslan, F; Yıldızoğlu, Ü; Durmaz, A; Çetinkaya, S

2018-05-01

In order to achieve a faster and more reliable anterior rhinomanometric evaluation, nasal skin was prepared using benzoin tincture solution, which provides simpler and better adhesion of the foam tape to the nasal skin. Two consecutive anterior rhinomanometry measurements were made, one with and one without benzoin tincture application. The average time taken to perform classic foam tape anterior rhinomanometry without benzoin tincture application was 281.32 seconds, and the average coefficients of variation for the right and left passages were 7.48 and 7.59 per cent, respectively. When benzoin tincture was used, the average time taken for completion of the tests was 121.24 seconds, and the average coefficients of variation for the right and left passages were 2.17 and 2.32 per cent. The use of benzoin tincture to clean the nasal skin before placing foam tape shortens the procedure duration and significantly increases test reliability.

Enantioselective production of benzoin from benzoin acetate via kinetic resolution and deracemization using Rhizopus oryzae.

PubMed

Songür, Rahime; Lurçi, Binnaz; Bayraktar, Emine; Mehmetoğlu, Ulkü; Demir, Ayhan S

2011-06-01

In this study, the production of enantiopure benzoin from rac-benzoin acetate was achieved by lipase catalyzed kinetic resolution combined with deracemization using Rhizopus oryzae (CBS111718). The growth cells were pretreated with 20 kHz and 30 kHz ultrasound irradiation and mechanical homogenization. Approximately 100% conversion and 96% enantiomeric excess of the product (S-benzoin) were obtained by applying 20 kHz ultrasound irradiation at pH 6. The deracemization process involves new and important processes that allow for the transformation of a racemate into a single stereoisomeric product in 100% theoretical yields. Moreover, the application of ultrasound increases the conversion rate by reducing mass transfer limitation.

Severe allergic contact dermatitis resulting from occupational exposure to tincture of benzoin aerosol spray in an anesthesiologist.

PubMed

Klein, Thomas G; Woehlck, Harvey J; Pagel, Paul S

2009-01-01

We describe the clinical presentation and management of an anesthesiologist who developed a severe allergic contact dermatitis resulting from occupational exposure to tincture of benzoin aerosol spray. A previously healthy male anesthesiologist with a small laceration between his right thumb and forefinger used a tincture of benzoin aerosol spray to improve adhesion of a small bandage immediately before performing a spinal anesthetic. He had previously used benzoin for skin reinforcement on several occasions during weight-lifting. The anesthesiologist experienced severe pruritus in the affected hand 48 h after benzoin exposure. A well-demarcated, bright red erythematous confluent vesicular dermatitis with and without painful hemorrhagic bullae erupted on the palmar and dorsal surfaces, respectively, of his hand, accompanied by pronounced edema. The palmar bullae were drained with several small incisions and the anesthesiologist was treated with intravenous methylprednisolone. He was unable to work for 10 days while the dermatitis gradually resolved. The case emphasizes that occupational exposure to benzoin represents a potential risk for operating room personnel who may be susceptible to cutaneous delayed hypersensitivity-mediated allergic reactions as a result of previous exposure to benzoin or chemically related cross-reacting substances.

Bis(amino)cyclopropenylidene (BAC) catalyzed aza-benzoin reaction.

PubMed

Wilde, Myron M D; Gravel, Michel

2014-10-17

A bis(amino)cyclopropenylidene (BAC) catalyzed aza-benzoin reaction between aldehydes and phosphinoyl imines has been developed. The reaction is general with a wide range of aromatic aldehydes and aromatic imines. The reaction displays excellent chemoselectivity favoring aza-benzoin products over homobenzoin products.

Chiral separation of norlaudanosoline, laudanosoline, laudanosine, chlorthalidone, and three benzoin derivatives using amino acid based molecular micelles.

PubMed

Billiot, Fereshteh H; Billiot, Eugene J; Ng, Yuen Kwun; Warner, Isiah M

2006-02-01

In this study, 18 polymeric single amino acid and dipeptide surfactants are examined, and their performances, in terms of enantioselectivity, are compared for norlaudanosoline, laudanosoline, laudanosine, chlorthalidone, benzoin, benzoin methyl, and benzoin ethyl enantiomers. Several aspects of amino acid-based polymeric surfactants including comparison of single amino acid versus dipeptide, amino acid order, steric effect, and effect of the position of the chiral center of dipeptide surfactants on the chiral selectivity of these optically active compounds are discussed.

Modified chiral triazolium salts for enantioselective benzoin cyclization of enolizable keto-aldehydes: synthesis of (+)-sappanone B.

PubMed

Takikawa, Hiroshi; Suzuki, Keisuke

2007-07-05

Asymmetric synthesis of (+)-sappanone B (1), a natural product with a 3-hydroxy chromanone structure, was achieved via enantioselective benzoin cyclization by using a modified Rovis catalyst and triethylamine. This catalyst enabled the successful benzoin cyclization of readily enolizable keto-aldehydes.

Beyond benzoin condensation: trimerization of aldehydes via metal-free aerobic oxidative esterification of aldehydes with benzoin products in the presence of cyanide.

PubMed

Kim, Yoo-Jin; Kim, Na Yeun; Cheon, Cheol-Hong

2014-05-02

An unusual trimerization of aldehydes in the presence of cyanide via metal-free aerobic oxidative esterification under ambient conditions is described. Various aromatic aldehydes provided the corresponding oxidative esterification products in good to excellent yields. Mechanistic studies suggested that this reaction would proceed via a two-step sequence: cyanide-catalyzed benzoin condensation of aldehydes and subsequent aerobic oxidative esterification of aldehydes with the resultant benzoin products. The usefulness of this protocol was further demonstrated by converting the resulting trimeric products into other biologically important compounds.

Asymmetric synthesis of [2,3-(13)C(2),(15)N]-4-benzyloxy-5,6-diphenyl-2,3,5,6-tetrahydro-4H-oxazine-2-one via lipase TL-mediated kinetic resolution of benzoin: general procedure for the synthesis of [2,3-(13)C(2),(15)N]-L-alanine.

PubMed

Aoyagi, Y; Iijima, A; Williams, R M

2001-11-30

Lipase TL-mediated kinetic resolution of benzoin proceeded to give the corresponding optically pure (R)-benzoin (R)-1. On the other hand, (S)-benzoin O-acetate (S)-7 could be hydrolyzed without epimerization to give (S)-benzoin (S)-1 under alkaline conditions. Furthermore, both enantiomers of benzoin (1) were converted to [(15)N]-(1R,2S)- and (1S,2R)- 2-amino-1,2-diphenylethanol (3a and 3b), respectively, according to the procedure reported previously. [2,3-(13)C(2),(15)N]-(5S,6R)-4-benzyloxy-5,6-diphenyl-2,3,5,6-tetrahydro-4H-oxazine-2-one (10) was synthesized from ethyl [1,2-(13)C(2)]bromoacetate and (1R,2S)-2-amino-1,2-diphenylethanol (3b) in three steps. Finally, [2,3-(13)C(2),(15)N]-L-alanine (12) was prepared via alkylation of the lactone 10 and hydrogenation of the alkylated product 11.

Highly chemo- and enantioselective cross-benzoin reaction of aliphatic aldehydes and α-ketoesters.

PubMed

Thai, Karen; Langdon, Steven M; Bilodeau, François; Gravel, Michel

2013-05-03

An electron-deficient, valine-derived triazolium salt is shown to catalyze a highly chemo- and enantioselective cross-benzoin reaction between aliphatic aldehydes and α-ketoesters. This methodology represents the first high yielding and highly enantioselective intermolecular cross-benzoin reaction using an organocatalyst (up to 94% ee). Further diastereoselective reduction of the products gives access to densely oxygenated compounds with high chemo- and diastereoselectivity.

Insights into the Competing Mechanisms and Origin of Enantioselectivity for N-Heterocyclic Carbene-Catalyzed Reaction of Aldehyde with Enamide

NASA Astrophysics Data System (ADS)

Qiao, Yan; Chen, Xinhuan; Wei, Donghui; Chang, Junbiao

2016-12-01

Hydroacylation reactions and aza-benzoin reactions have attracted considerable attention from experimental chemists. Recently, Wang et al. reported an interesting reaction of N-heterocyclic carbene (NHC)-catalyzed addition of aldehyde to enamide, in which both hydroacylation and aza-benzoin reactions may be involved. Thus, understanding the competing relationship between them is of great interest. Now, density functional theory (DFT) investigation was performed to elucidate this issue. Our results reveal that enamide can tautomerize to its imine isomer with the assistance of HCO3-. The addition of NHC to aldehydes formed Breslow intermediate, which can go through cross-coupling with enamide via hydroacylation reaction or its imine isomer via aza-benzoin reaction. The aza-benzoin reaction requires relatively lower free energy barrier than the hydroacylation reaction. The more polar characteristic of C=N group in the imine isomers, and the more advantageous stereoelectronic effect in the carbon-carbon bond forming transition states in aza-benzoin pathway were identified to determine that the imine isomer can react with the Breslow intermediate more easily. Furthermore, the origin of enantioselectivities for the reaction was explored and reasonably explained by structural analyses on key transition states. The work should provide valuable insights for rational design of switchable NHC-catalyzed hydroacylation and aza-benzoin reactions with high stereoselectivity.

4D Interconnect Experimental Development

DTIC Science & Technology

1993-06-29

Polymerization of MMA Using Benzoyl Peroxide ..... .......... 6 2.1.2.3 Polymerization Using Benzoin ........ .................. 7 2.1.3 Adding the SHB...molecules.J6l This breakdown can be driven thermally (as in the case of benzoyl peroxide) or via UV illumination (as in the case of benzoin ). Once...taken is increased. 6 2.1.2.3 Polymerization Using Benzoin A commonly used alternative to the initiation being driven thermally is to use a photoini

Chemo- and Diastereoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions Using N-Boc-α-amino Aldehydes.

PubMed

Haghshenas, Pouyan; Gravel, Michel

2016-09-16

N-Boc-α-amino aldehydes are shown to be excellent partners in cross-benzoin reactions with aliphatic or heteroaromatic aldehydes. The chemoselectivity of the reaction and the facial selectivity on the amino aldehyde allow cross-benzoin products to be obtained in good yields and good diastereomeric ratios. The developed method is utilized as the key step in a concise total synthesis of d-arabino-phytosphingosine.

Substrate-Controlled Diastereoselectivity Reversal in NHC-Catalyzed Cross-Benzoin Reactions Using N-Boc-N-Bn-Protected α-Amino Aldehydes.

PubMed

Haghshenas, Pouyan; Quail, J Wilson; Gravel, Michel

2016-12-16

The effectiveness of utilizing N-Bn-N-Boc-α-amino aldehydes in cross-benzoin reactions with heteroaromatic aldehydes is demonstrated. The reaction is both chemoselective and syn-selective, making it complementary to the anti-selective cross-benzoin reaction of NHBoc-α-amino aldehydes. Good diastereoselectivity is obtained for a variety of amino aldehydes, including nonhindered ones. A Felkin-Anh model can be used to rationalize the observed diastereoselectivity.

Chiral micellar electrokinetic chromatography (CMEKC)-atmospheric pressure photoionization of benzoin derivatives using mixed molecular micelles

PubMed Central

He, Jun; Shamsi, Shahab A.

2012-01-01

In the present work we report, for the first time, the successful on-line coupling of chiral micellar electrokinetic chromatography (CMEKC) to atmospheric pressure photo-ionization mass spectrometry (APPI-MS). Four structurally similar neutral test solutes (e.g., benzoin derivatives) were successfully ionized by APPI-MS. The mass spectra in the positive ion mode showed that the protonated molecular ions of benzoins are not the most abundant fragment ions. Simultaneous enantioseparation by CMEKC and on-line APPI-MS detection of four photoinitiators: hydrobenzoin (HBNZ), benzoin (BNZ), benzoin methyl ether (BME), benzoin ethyl ether (BEE), were achieved using an optimized molar ratio of mixed molecular micelle of two polymeric chiral surfactants (polysodium N-undecenoxy carbonyl-L-leucinate and polysodium N-undecenoyl-L,L-leucylvalinate). The CMEKC conditions, such as voltage, chiral polymeric surfactant concentration, buffer pH, and BGE concentration, were optimized using a multivariate central composite design (CCD). The sheath liquid composition (involving % v/v methanol, dopant concentration, electrolyte additive concentration, and flow rate) and spray chamber parameters (drying gas flow rate, drying gas temperature, and vaporizer temperature) were also optimized with CCD. Models built based on the CCD results and response surface method was used to analyze the interactions between factors and their effects on the responses. The final overall optimum conditions for CMEKC-APPI-MS were also predicted and found in agreement with the experimentally optimized parameters. PMID:21500208

Insights into the Competing Mechanisms and Origin of Enantioselectivity for N-Heterocyclic Carbene-Catalyzed Reaction of Aldehyde with Enamide

PubMed Central

Qiao, Yan; Chen, Xinhuan; Wei, Donghui; Chang, Junbiao

2016-01-01

Hydroacylation reactions and aza-benzoin reactions have attracted considerable attention from experimental chemists. Recently, Wang et al. reported an interesting reaction of N-heterocyclic carbene (NHC)-catalyzed addition of aldehyde to enamide, in which both hydroacylation and aza-benzoin reactions may be involved. Thus, understanding the competing relationship between them is of great interest. Now, density functional theory (DFT) investigation was performed to elucidate this issue. Our results reveal that enamide can tautomerize to its imine isomer with the assistance of HCO3−. The addition of NHC to aldehydes formed Breslow intermediate, which can go through cross-coupling with enamide via hydroacylation reaction or its imine isomer via aza-benzoin reaction. The aza-benzoin reaction requires relatively lower free energy barrier than the hydroacylation reaction. The more polar characteristic of C=N group in the imine isomers, and the more advantageous stereoelectronic effect in the carbon-carbon bond forming transition states in aza-benzoin pathway were identified to determine that the imine isomer can react with the Breslow intermediate more easily. Furthermore, the origin of enantioselectivities for the reaction was explored and reasonably explained by structural analyses on key transition states. The work should provide valuable insights for rational design of switchable NHC-catalyzed hydroacylation and aza-benzoin reactions with high stereoselectivity. PMID:27905524

Contribution of insectivorous avifauna to top down control of Lindera benzoin herbivores at forest edge and interior habitats

NASA Astrophysics Data System (ADS)

Skoczylas, Daniel R.; Muth, Norris Z.; Niesenbaum, Richard A.

2007-11-01

Predation of herbivorous Lepidoptera larvae by insectivorous avifauna was estimated on Lindera benzoin in edge and interior habitats at two sites in eastern Pennsylvania (USA). Clay baits modeled after Epimecis hortaria (Geometridae) larvae, the primary herbivore of L. benzoin at our study sites, were used to estimate predation by birds. In both habitat types, models were placed on uninjured L. benzoin leaves as well as on leaves that had prior insect herbivore damage. Rates of model attack were greater, and model longevity reduced, in forest edge plots compared to interiors. Naturally occurring herbivore damage on L. benzoin was greater in forest interiors. However, model attack was not significantly greater on leaves with prior herbivory damage, suggesting that birds do not effectively use this type of leaf damage as a cue in their foraging. Our findings are consistent with a contribution of bird predation towards top-down control of herbivory in this system. We further discuss these results in a broader context considering the possible effects of habitat type on leaf quality, leaf defense, and herbivore performance.

Benzoin Radicals as Reducing Agent for Synthesizing Ultrathin Copper Nanowires.

PubMed

Cui, Fan; Dou, Letian; Yang, Qin; Yu, Yi; Niu, Zhiqiang; Sun, Yuchun; Liu, Hao; Dehestani, Ahmad; Schierle-Arndt, Kerstin; Yang, Peidong

2017-03-01

In this work, we report a new, general synthetic approach that uses heat driven benzoin radicals to grow ultrathin copper nanowires with tunable diameters. This is the first time carbon organic radicals have been used as a reducing agent in metal nanowire synthesis. In-situ temperature dependent electron paramagnetic resonance (EPR) spectroscopic studies show that the active reducing agent is the free radicals produced by benzoins under elevated temperature. Furthermore, the reducing power of benzoin can be readily tuned by symmetrically decorating functional groups on the two benzene rings. When the aromatic rings are modified with electron donating (withdrawing) groups, the reducing power is promoted (suppressed). The controllable reactivity gives the carbon organic radical great potential as a versatile reducing agent that can be generalized in other metallic nanowire syntheses.

Asymmetric reduction of benzil to (S)-benzoin with Penicillium claviforme IAM 7294 in a liquid-liquid interface bioreactor (L-L IBR).

PubMed

Oda, Shinobu; Isshiki, Kunio

2008-05-01

The asymmetric reduction of benzyl to (S)-benzoin with Penicillium claviforme IAM 7294 was applied to a liquid-liquid interface bioreactor (L-L IBR) using a unique polymeric material, ballooned microsphere (MS). The L-L IBR showed superior performance, as compared with suspension, organic-aqueous two-liquid-phase, and solid-liquid interface bioreactor (S-L IBR) systems, affording 14.4 g/l-organic phase of (S)-benzoin (99.0% ee).

Oxidation of Benzoin by Hexacyanoferrate (III)

ERIC Educational Resources Information Center

Jarrar, Adil A.; El-Zaru, Ribhi

1977-01-01

Describes a kinetics experiment in which the student measures both a second-order rate constant and an overall third-order rate constant for the oxidation of benzoin to benzil in an alkaline medium. (MLH)

Lanthanum tricyanide-catalyzed acyl silane-ketone benzoin additions.

PubMed

Tarr, James C; Johnson, Jeffrey S

2009-09-03

Lanthanum tricyanide efficiently catalyzes a benzoin-type coupling between acyl silanes and ketones. Yields range from moderate to excellent over a broad substrate scope encompassing aryl, alkyl, electron-rich, and sterically hindered ketones.

Information profiles on potential occupational hazards: benzoin

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

Not Available

1981-03-01

Information on potential occupational hazards from exposure to benzoin was reviewed. Topics discussed included chemical and physical properties, production, uses, manufacturers and distributors, manufacturing processes, occupational exposure, and biological effects. The annual production of benzoin is approximately 90,000 pounds per year with an historical growth rate of about 6% per year. In carcinogenesis studies, the incidence of lymphomas and leukemia in dosed male rats increased with dose level, but not significantly. Mice demonstrated a significant increase in the incidence of lymphomas and leukemias at low dose levels. Bioassays have indicated that benzoin is not carcinogenic to male or female F344-ratsmore » or B6C3F1-mice. No evidence of mutagenicity, teratogenicity, or reproductive effects was found in animal studies. Allergic contact dermatitis has been reported in humans.« less

Isolation and reconstitution of cytochrome P450ox and in vitro reconstitution of the entire biosynthetic pathway of the cyanogenic glucoside dhurrin from sorghum.

PubMed Central

Kahn, R A; Bak, S; Svendsen, I; Halkier, B A; Møller, B L

1997-01-01

A cytochrome P450, designated P450ox, that catalyzes the conversion of (Z)-p-hydroxyphenylacetaldoxime (oxime) to p-hydroxymandelonitrile in the biosynthesis of the cyanogenic glucoside beta-D-glucopyranosyloxy-(S)-p-hydroxymandelonitrile (dhurrin), has been isolated from microsomes prepared from etiolated seedlings of sorghum (Sorghum bicolor L. Moench). P450ox was solubilized using nonionic detergents, and isolated by ion-exchange chromatography, Triton X-114 phase partitioning, and dye-column chromatography. P450ox has an apparent molecular mass of 55 kD, its N-terminal amino acid sequence is -ATTATPQLLGGSVP, and it contains the internal sequence MDRLVADLDRAAA. Reconstitution of P450ox with NADPH-P450 oxidoreductase in micelles of L-alpha-dilauroyl phosphatidylcholine identified P450ox as a multifunctional P450 catalyzing dehydration of (Z)-oxime to p-hydroxyphenylaceto-nitrile (nitrile) and C-hydroxylation of p-hydroxyphenylacetonitrile to nitrile. P450ox is extremely labile compared with the P450s previously isolated from sorghum. When P450ox is reconstituted in the presence of a soluble uridine diphosphate glucose glucosyltransferase, oxime is converted to dhurrin. In vitro reconstitution of the entire dhurrin biosynthetic pathway from tyrosine was accomplished by the insertion of CYP79 (tyrosine N-hydroxylase), P450ox, and NADPH-P450 oxidoreductase in lipid micelles in the presence of uridine diphosphate glucose glucosyltransferase. The catalysis of the conversion of Tyr into nitrile by two multifunctional P450s explains why all intermediates in this pathway except (Z)-oxime are channeled. PMID:9414567

Theoretical and experimental study of the conformational and vibrational properties of benzoin

NASA Astrophysics Data System (ADS)

Pawelka, Zbignew; Kryachko, Eugene S.; Zeegers-Huyskens, Thérèse

2003-02-01

The conformational and vibrational properties of benzoin are theoretically studied at the B3LYP/6-31+G(d,p) computational level. Three lower energy stable structures are found on its potential energy surface. The two first structures correspond to cis- and trans-benzoin. The cis isomer, stabilized by an intramolecular OH⋯O hydrogen bond, is more favorable by 3.4 kcal mol -1 over the trans isomer. The third structure refers to the dienol tautomer ( cis-stilbendiol) which is less stable by 7.6 kcal mol -1. In carbon tetrachloride, benzoin is in the cis conformation. The calculated vibrational frequencies are compared with the experimental ones. When the ν(OH) and ν(CH) vibrations are corrected for anharmonicities, an average scaling factor of 0.980 is deduced. The IR and Raman spectra of solid benzoin are analyzed as well and discussed in terms of the structure determined by X-ray diffraction [Acta crystallogr. B 36 (1980) 2832]. The isotopic ratio ν(OH)/ ν(OD) reflects the weakness of the intramolecular hydrogen bond in solution and of the intermolecular hydrogen bond in the solid state. This weakness can be accounted for by the great departure of the hydrogen bond from linearity.

Lanthanum Tricyanide-Catalyzed Acyl Silane-Ketone Benzoin Additions

PubMed Central

Tarr, James C.; Johnson, Jeffrey S.

2009-01-01

Lanthanum tricyanide efficiently catalyzes a benzoin-type coupling between acyl silanes and ketones. Yields range from moderate to excellent over a broad substrate scope encompassing aryl, alkyl, electron-rich, and sterically hindered ketones. PMID:19655731

Nature Inspired Strategies for New Organic Materials

DTIC Science & Technology

2007-01-14

8217/. Compound Side-products: lir- NOH Ar AH ÷ R IS Ar • R Ph Ph 65 3a Ar benzoin product Ph NHDF 04 Ar-1A- bnzinpodcNaH/DMF Ph Ph H 61 3b 1 2 up to 65% yield...NHC-Catalyzed Acylatlon0 process is depicted in Scheme 2. The major N 0 side products of the reaction were identified o as benzoin -type products...derived from the Ph 3C\\NJM Ar H addition of intermediate IV to the starting carbene aldehyde) and more importantly, the acylated benzoin adduct 4

NHC-Catalyzed Asymmetric Benzoin Reaction in Water.

PubMed

Yan, Jun; Sun, Rong; Shi, Kuangxi; Li, Kai; Yang, Limin; Zhong, Guofu

2018-06-11

A chiral NHC-catalyzed benzoin condensation reaction in water was developed, thereby affording α-hydroxy ketones in good to high yields and high enantioselectivities. Water was proposed as a proton shuttle in the aqueous asymmetric condensation reaction.

Origin of chemoselectivity in N-heterocyclic carbene catalyzed cross-benzoin reactions: DFT and experimental insights.

PubMed

Langdon, Steven M; Legault, Claude Y; Gravel, Michel

2015-04-03

An exploration into the origin of chemoselectivity in the NHC-catalyzed cross-benzoin reaction reveals several key factors governing the preferred pathway. In the first computational study to explore the cross-benzoin reaction, a piperidinone-derived triazolium catalyst produces kinetically controlled chemoselectivity. This is supported by (1)H NMR studies as well as a series of crossover experiments. Major contributors include the rapid and preferential formation of an NHC adduct with alkyl aldehydes, a rate-limiting carbon-carbon bond formation step benefiting from a stabilizing π-stacking/π-cation interaction, and steric penalties paid by competing pathways. The energy profile for the analogous pyrrolidinone-derived catalyst was found to be remarkably similar, despite experimental data showing that it is less chemoselective. The chemoselectivity could not be improved through kinetic control; however, equilibrating conditions show substantial preference for the same cross-benzoin product kinetically favored by the piperidinone-derived catalyst.

A structure-activity analysis of the variation in oxime efficacy against nerve agents

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

Maxwell, Donald M.; Koplovitz, Irwin; Worek, Franz

2008-09-01

A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k{sub r2}) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and inmore » vitro k{sub r2} decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (< 3.7-fold decrease in PR). The decrease in oxime PR and k{sub r2} as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k{sub r2} {center_dot} [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy.« less

New insights in the chemical composition of benzoin balsams.

PubMed

Burger, Pauline; Casale, Alexandre; Kerdudo, Audrey; Michel, Thomas; Laville, Rémi; Chagnaud, Francis; Fernandez, Xavier

2016-11-01

Benzoin balsam is an anthropic exudate obtained from the bark of several species of Styrax trees that is mainly used as a perfume fixative as well as a flavouring agent. Benzoe tonkinensis Laos (also commercialized under the denomination Siam benzoin balsam) displaying characteristic vanilla notes and already being largely used to flavour all kinds of edible goods, was intended to be proposed by Agroforex Company to the Codex Committee on Food Additives for evaluation as a food additive. For this purpose, the present paper reports the phytochemical characterisation of both the volatile and non-volatile fractions of benzoin balsams and the quantitation of some of the major components by gas and liquid chromatography techniques. Four coniferyl and two morinol derivatives were characterised for the first time in Benzoe tonkinensis Laos. Finally, two liquid chromatographic methods used to easily discriminate Siam from Sumatra balsam (also known as Benzoe sumatranus Indonesia) were developed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Studies on the chemical stability and functional group compatibility of the benzoin photolabile safety-catch linker using an analytical construct.

PubMed

Cano, Montserrat; Ladlow, Mark; Balasubramanian, Shankar

2002-01-01

A chemical stability study of the benzoin photolabile safety-catch linker (BPSC) has been carried out using a dual-linker analytical construct to establish its compatibility with a range of commonly employed solid-phase reaction conditions. As a result of this study, the dithiane-protected benzoin linker was shown to be reactive only toward strong acids and fluoride nucleophile. Furthermore, a scan of diverse functional groups thought to be unstable toward the safety-catch removal conditions has also been carried out. These data should provide assistance in future utilization of the BPSC for syntheses.

Influence of solvents on the conformation of benzoin

NASA Astrophysics Data System (ADS)

Pawełka, Z.; Czarnik-Matusewicz, B.; Zeegers-Huyskens, Th.

2010-01-01

The conformation of benzoin in several organic solvents is investigated by infrared spectrometry and dipolometry. The frequencies, intensities, and band shapes of the ν(OH), ν(C dbnd O), and aromatic ring vibrations indicate that in solvents of low proton acceptor ability, the cis conformer with intramolecular OH···O hydrogen bonding is preserved. In solvents of large proton acceptor ability there is equilibrium between the cis and trans conformers. The dipole moments are less sensitive to conformational changes, but indicate the same trends. The results are discussed as a function of the specific solvation of the O atoms or OH groups of benzoin.

Influence of solvents on the conformation of benzoin.

PubMed

Pawełka, Z; Czarnik-Matusewicz, B; Zeegers-Huyskens, Th

2010-01-01

The conformation of benzoin in several organic solvents is investigated by infrared spectrometry and dipolometry. The frequencies, intensities, and band shapes of the nu(OH), nu(C=O), and aromatic ring vibrations indicate that in solvents of low proton acceptor ability, the cis conformer with intramolecular OH...O hydrogen bonding is preserved. In solvents of large proton acceptor ability there is equilibrium between the cis and trans conformers. The dipole moments are less sensitive to conformational changes, but indicate the same trends. The results are discussed as a function of the specific solvation of the O atoms or OH groups of benzoin. Copyright 2009 Elsevier B.V. All rights reserved.

Asymmetric Desymmetrization of 1,3-Diketones via Intramolecular Benzoin Reaction.

PubMed

Li, Yuanzhen; Yang, Shuang; Wen, Genfa; Lin, Qiqiao; Zhang, Guoxiang; Qiu, Lin; Zhang, Xiaoyan; Du, Guangfen; Fang, Xinqiang

2016-04-01

A general method for the asymmetric desymmetrization of 1,3-diketone substrates via chiral N-heterocyclic carbene catalyzed intramolecular benzoin reactions was developed. Five- and six-membered cyclic ketones bearing two contiguous fully substituted stereocenters were generated with excellent diastereoselectivities and moderate to excellent enantioselectivities.

Antibody-catalyzed benzoin oxidation as a mechanistic probe for nucleophilic catalysis by an active site lysine.

PubMed

Sklute, Genia; Oizerowich, Rachel; Shulman, Hagit; Keinan, Ehud

2004-05-03

Aldolase antibody 24H6, which was obtained by reactive immunization against a 1,3-diketone hapten, is shown to catalyze additional reactions, including H/D exchange and oxidation reactions. Comparison of the H/D exchange reaction at the alpha-position of a wide range of aldehydes and ketones by 24H6 and by other aldolase antibodies, such as 38C2, pointed at the significantly larger size of the 24H6 active site. This property allowed for the catalysis of the oxidation of substituted benzoins to benzils by potassium ferricyanide. This reaction was used as a mechanistic probe to learn about the initial steps of the 24H6-catalyzed aldol condensation reaction. The Hammett correlation (rho=4.7) of log(k(cat)) versus the substituent constant, sigma, revealed that the reaction involves rapid formation of a Schiff base intermediate from the ketone and an active site lysine residue. The rate-limiting step in this oxidation reaction is the conversion of the Schiff base to an enamine intermediate. In addition, linear correlation (rho=3.13) was found between log(K(M)) and sigma, indicating that electronic rather than steric factors are dominant in the antibody-substrate binding phenomenon and confirming that the reversible formation of a Schiff base intermediate comprises part of the substrate-binding mechanism.

Nerve Agent Induced Status Epilepticus: From Seizure Onset to Long Lasting Pathology

DTIC Science & Technology

2014-01-31

of oximes in the treatment of nerve agent poisoning in civilian casualties. Toxicol Rev 25:297-323 168. Martin LF, Kem WR, Freedman R. 2004. Alpha-7...Pharmacol 82:931-42 220. Paxinos G, Watson C. 2005. The Rat Brain in Stereotaxic Coordinates. New York NY: Elsevier 221. Petras JM. 1981. Soman...neurotoxicity. Fundam Appl Toxicol 1 :242 222. Petras JM. 1994. Neurology and neuropathology of Soman-induced brain injury: an overview. J Exp Anal

Highly chemoselective intermolecular cross-benzoin reactions using an ad hoc designed novel N-heterocyclic carbene catalyst.

PubMed

Delany, Eoghan G; Connon, Stephen J

2018-01-31

The design of a novel N-heterocyclic carbene catalyst incorporating a bulky yet highly electron-deficient N-aryl substituent has allowed the development of an efficient protocol for the first highly chemoselective intermolecular benzoin condensations between two non-identical aromatic aldehydes.

Moisture-Resistant Adhesives.

DTIC Science & Technology

1982-05-01

34Synthesis of Monomers and Polymers for Evaluation." The 4-nitrobenzoin acetate was prepared by nitrating benzoin in acetic anhydride. Yields of 33...Reference 3). (1) 4-Nitrobenzoin acetate: A suspension of 250 g (1.18 moles) of benzoin in 930 ml of acetic anhydride was cooled to 15*C and 40 ml of

Electron Microscopy of Intracellular Protozoa

DTIC Science & Technology

1988-12-20

LR Gold resin containing 0.75% (w/v) benzoin methyl ether as an ultraviolet initiator and left overnight in fresh resin. The samples were finally...ethanol at progressively lower temperatures between OC and -20°C, and infiltrated with LR Gold resin containing 0.5% w/w benzoin methyl ether as an

Scalability of the LEU-Modified Cintichem Process: 3-MeV Van de Graaff and 35-MeV Electron Linear Accelerator Studies

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

Rotsch, David A.; Brossard, Tom; Roussin, Ethan

Molybdenum-99, the mother of Tc-99m, can be produced from fission of U-235 in nuclear reactors and purified from fission products by the Cintichem process, later modified for low-enriched uranium (LEU) targets. The key step in this process is the precipitation of Mo with α-benzoin oxime (ABO). The stability of this complex to radiation has been examined. Molybdenum-ABO was irradiated with 3 MeV electrons produced by a Van de Graaff generator and 35 MeV electrons produced by a 50 MeV/25 kW electron linear accelerator. Dose equivalents of 1.7–31.2 kCi of Mo-99 were administered to freshly prepared Mo-ABO. Irradiated samples of Mo-ABOmore » were processed according to the LEU Modified-Cintichem process. The Van de Graaff data indicated good radiation stability of the Mo-ABO complex up to ~15 kCi dose equivalents of Mo-99 and nearly complete destruction at doses >24 kCi Mo-99. The linear accelerator data indicate that even at 6.2 kCi of Mo-99 equivalence of dose, the sample lost ~20% of Mo-99. The 20% loss of Mo-99 at this low dose may be attributed to thermal decomposition of the product from the heat deposited in the sample during irradiation.« less

DNA damage in mouse and rat liver by caprolactam and benzoin, evaluated with three different methods.

PubMed

Parodi, S; Abelmoschi, M L; Balbi, C; De Angeli, M T; Pala, M; Russo, P; Taningher, M; Santi, L

1989-11-01

Benzoin and caprolactam were examined for their capability of inducing alkaline DNA fragmentation in mouse and rat liver DNA after treatment in vivo. Three different methods were used. With the alkaline elution technique we measured an effect presumably related to the conformation of the DNA coil. With a viscometric and a fluorometric unwinding method we measured an effect presumably related to the number of unwinding points in DNA. For both compounds only the alkaline elution technique was clearly positive. The results suggest that both caprolactam and benzoin can induce an important change in the conformation of the DNA coil without inducing true breaks in DNA.

Advances in chemoselective intermolecular cross-benzoin-type condensation reactions.

PubMed

Gaggero, Nicoletta; Pandini, Stefano

2017-08-23

The intermolecular cross-benzoin and acyloin condensation reactions are powerful approaches to α-hydroxy carbonyls in a single step. However, their potentiality suffers from the occurrence of side reactions including self-condensation and the formation of the undesired cross-acyloin. The broad range of azolium salt precatalysts available confers high tunability to NHC mediated benzoin condensation, assuring a good level of selectivity to the direct coupling between two non-equivalent aldehydes. Many efforts have also been devoted to the design of strategies that expand the range of suitable reaction partners beyond the traditional aldehydes and to the discovery of novel umpolung catalytic systems. The synthesis of both racemic and enantiomerically enriched acyloins is reviewed.

Effects of Head-Supported Devices on Female Aviators during Simulated Helicopter Missions

DTIC Science & Technology

1998-05-01

gram Plexiglas mounts. These mounts will be attached to the skin using tincture of benzoin , collodion, and sticky pads (to hold the mount in place...and sternum, a technician will vigorously rub the areas with an alcohol pad and then with tincture of benzoin . Collodion, an adhesive substance, will

N-heterocyclic carbene-catalyzed tandem aza-benzoin/Michael reactions: on site reversal of the reactivity of N-Boc imines.

PubMed

Wu, Ke-Jia; Li, Gong-Qiang; Li, Yi; Dai, Li-Xin; You, Shu-Li

2011-01-07

A tandem NHC-catalyzed aza-benzoin/Michael reaction has been developed as a method to efficiently produce dihydroindenones and pyrrolidinone-containing tricycles. The novel reaction pattern involves tert-butyl aryl(tosyl)methylcarbamates reacting as both electrophile and nucleophile on the same carbon.

N-heterocyclic carbene catalysed asymmetric cross-benzoin reactions of heteroaromatic aldehydes with trifluoromethyl ketones.

PubMed

Enders, Dieter; Grossmann, André; Fronert, Jeanne; Raabe, Gerhard

2010-09-14

A new triazolium salt derived N-heterocyclic carbene catalyses an asymmetric cross-benzoin-type reaction of heteroaromatic aldehydes and various trifluoromethyl ketones in good to excellent yields (69-96%) and moderate to good enantioselectivities (ee = 39-85%). Up to 99% ee can be achieved by recrystallisation.

Antibacterial, anti-biofilm and anticancer potentials of green synthesized silver nanoparticles using benzoin gum (Styrax benzoin) extract.

PubMed

Du, Juan; Singh, Hina; Yi, Tae-Hoo

2016-12-01

This study described a simple and green approach for the synthesis of silver nanoparticles (AgNPs) employing benzoin gum water extract as a reducing and capping agent and their applications. The AgNPs were characterized by ultraviolet-visible spectrophotometer, X-ray diffraction pattern, field emission transmission electron microscopy, dynamic light scattering, zeta potential and fourier transform infrared spectroscopy. The AgNPs showed promising antimicrobial activity against various pathogens (Gram-negative, Gram-positive and fungus) and possessed high free radical scavenging activity (104.5 ± 7.21 % at 1 mg/ml). In addition, the AgNPs exhibited strong cytotoxicity towards human cervical cancer and human lung cancer cells as compared to the normal mouse macrophage cells. Moreover, the AgNPs possessed anti-biofilm activity against Escherichia coli, and compatibility to human keratinocyte HaCaT cells, which suggests the use of dressing with the AgNPs in chronic wound treatment. Therefore, AgNPs synthesized by benzoin gum extract are comparatively green and may have broad spectrum potential application in biomedicine.

Oximes in organophosphate poisoning: 60 years of hope and despair.

PubMed

Worek, Franz; Thiermann, Horst; Wille, Timo

2016-11-25

The high number of annual fatalities following suicidal poisoning by organophosphorus (OP) pesticides and the recent homicidal use of the chemical warfare nerve agent sarin against civilian population in Syria underlines the continuous threat by these highly toxic agents. The need for an effective treatment of OP poisoning resulted in the implementation of a combination therapy with the muscarinic receptor antagonist atropine and an oxime for the reactivation of OP-inhibited acetylcholinesterase (AChE). Since the invention of the first clinically used oxime pralidoxime (2-PAM) in the 1950s ongoing research attempted to identify more effective oximes. In fact, several thousand oximes were synthesized in the past six decades. These include charged and non-charged compounds, mono- and bispyridinium oximes, asymmetric oximes, oximes with different substitutes and more recently non-oxime reactivators. Multiple in vitro and in vivo studies investigated the potential of oximes to reactivate OP-inhibited AChE and to reverse OP-induced cholinergic signs. Depending on the experimental model, the investigated species and the tested OP largely variable results were obtained by different laboratories. These findings and the inconsistent effectiveness of oximes in the treatment of OP-pesticide poisoned patients led to a continuous discussion on the value of oximes. In order to provide a forward-looking evaluation of the significance of oximes in OP poisoning multiple aspects, including intrinsic toxicity, in vitro reactivation potency, efficacy and pharmacokinetics, as well as the impact of the causative OP have to be considered. The different influencing factors in order to define the benefit and limitations of oximes in OP poisoning will be discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A comparison of the reactivating and therapeutic efficacy of chosen combinations of oximes with individual oximes against VX in rats and mice.

PubMed

Kassa, Jiri; Karasova, Jana Zdarova; Sepsova, Vendula; Caisberger, Filip; Bajgar, Jiri

2011-10-01

The ability of 2 combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to reactivate VX-inhibited acetylcholinesterase and reduce acute toxicity of VX was compared with the reactivating and therapeutic efficacy of antidotal treatment involving a single oxime (HI-6, trimedoxime, K203) in rats and mice. Our results showed that the reactivating efficacy of both combinations of oximes studied in rats is significantly higher than the reactivating efficacy of all individual oximes in diaphragm and roughly corresponds to the most effective individual oxime in blood and brain. Both combinations of oximes were found to be more effective in the reduction of acute lethal toxicity of VX in mice than the antidotal treatment involving the most efficacious individual oxime although the difference is not significant. Based on the obtained data, we can conclude that the antidotal treatment involving the chosen combinations of oximes brings benefit for the reactivation of VX-inhibited acetylcholinesterase in rats and for the antidotal treatment of VX-induced acute poisoning in mice.

A comparison of the efficacy of new asymmetric bispyridinium oximes (K027, K048) with currently available oximes against tabun by in vivo methods.

PubMed

Kassa, Jiri; Kuca, Kamil; Cabal, Jiri; Paar, Martin

2006-10-01

The potency of newly developed asymmetric bispyridinium oximes (K027, K048) in reactivating tabun-inhibited acetylcholinesterase (AChE) and in eliminating tabun-induced acute toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined the percent of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime, the most efficacious known reactivators of tabun-inhibited AChE. These were also found to be sufficiently efficacious in the elimination of acute lethal toxic effects in tabun-poisoned rats. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and in counteracting acute lethal effects of tabun. In addition, our results confirm that the efficacy of oximes in reactivating tabun-inhibited AChE in blood, diaphragm, and brain correlates with the potency of oximes in protecting rats poisoned with supralethal doses of tabun.

An intramolecular crossed-benzoin reaction based KCN fluorescent probe in aqueous and biological environments.

PubMed

Lee, Jae Hong; Jang, Joo Hee; Velusamy, Nithya; Jung, Hyo Sung; Bhuniya, Sankarprasad; Kim, Jong Seung

2015-05-04

A turn-on fluorescent probe was designed for selective cyanide anion sensing in aqueous and biological environments. The probe underwent an intramolecular crossed-benzoin reaction in the presence of KCN to expel the fluorophore resorufin. This probe was sensitive to KCN concentrations as low as 4 nM in aqueous media.

N-Heterocyclic carbene-catalyzed chemoselective cross-aza-benzoin reaction of enals with isatin-derived ketimines: access to chiral quaternary aminooxindoles.

PubMed

Xu, Jianfeng; Mou, Chengli; Zhu, Tingshun; Song, Bao-An; Chi, Yonggui Robin

2014-06-20

A chemo- and enantioselective cross-aza-benzoin reaction between enals and isatin-derived ketimines is disclosed. The high chemoselectivity (of the acyl anion reaction over enal α- and β-carbon reactions) is enabled by the electronic and steric properties of the N-heterocyclic carbene organocatalyst.

Integration of active and passive microwave signatures for characterization of soil properties

NASA Astrophysics Data System (ADS)

Laulhe, Sebastien

The reaction between an aminooxy moiety (RONH2) and a carbonyl group of either an aldehyde or a ketone --- known as an oximation reaction --- is a versatile click chemistry coupling that generates a robust oxime ether linkage. The oximation reaction is chemoselective and can be performed under mild conditions in a large variety of solvents, including water. The attractive properties of the aminooxy group and derived oximation reactions, reviewed in Chapter 1, inspired us to use this chemistry as a key feature of our research. Specifically, we prepare functionalized aminooxy compounds so that the oximation chemistry can then serve as a prelude to new synthetic or analytical methods. For example, Chapter 2 presents an improved preparation of O-(diphenylphosphinyl)hydroxylamine (DPPH), an aminooxy-containing reagent, using the classic Schotten-Baumann conditions. We show how DPPH can then be used as a chemoselective nitrogen transfer reagent for a one-pot aldehyde-to-nitrile functional group transformation. Sixteen aldehydes were smoothly transformed to their corresponding nitriles by heating at 85 °C with DPPH in toluene. The reaction can be accomplished in the presence of alcohol, ketone, ester, or amine functionality. In another application, we use functionalized aminooxy reagents to achieve quantitative multiplexed gas chromatography-mass spectrometry (GC-MS) analysis. Specifically, we chemoselectively derivatize carbonyl (aldehyde and ketone) metabolites using the aminooxy-containing reagents. Chapter 3 presents a focused fundamental study of the propensity of oxime ethers to undergo MS-induced fragmentations, such as the McLafferty rearrangement. In particular, we studied structural factors that promoted alpha,beta-fragmentation in oximes of both ketones and aldehydes, as well as the derived silyl ethers of these adducts. We determined that 1) the propensity of the McLafferty rearrangement was greatly enhanced by oxygen at the b-position of silyl oxime ethers, 2) the McLafferty rearrangement is more prominent for E-isomers of oxime and silyl oxime ethers than for the corresponding Z-isomers, and 3) Z-isomers of silyl oxime ethers with CH2 at the b-position generate nitrilium ions to a greater extent than their corresponding E-isomers. Chapter 4 describes the 3-step synthesis of a new class of stable isotope-labeled derivatizing reagents ---- a&barbelow;minooxye&barbelow;thyl p&barbelow;ropionate reagents (AEP) ---- that enable multiplexed GC-MS analysis of small molecule carbonyl compounds. The AEP reagents contain 1) an aminooxy moiety, and 2) a propionate ester moiety that generates a reporter isotope-labeled mass spectral tag (MST) in the form of an ethyl carbenium ion via an ester a-cleavage. The AEP MSTs appear in an m/z zone of minimal interference (ZMI) in the range m/z 32-34. This is a key feature in that unobstructed observation of reporter MSTs in this zone significantly improves simultaneous quantitation of carbonyl analytes from multiple samples without recourse to MS peak deconvolution strategies. Also, and in contrast to known isotope coding reagents for GC-MS, AEP reagents are not affected by the chromatographic isotope effect. The versatility of the technology for carbonyl metabolite profiling and absolute quantification is demonstrated by an analysis of turmeric extract, serving as a representative complex biological sample. A series of analogous methyl ketones were profiled from characteristic MS fragmentations of the AEP-derived oxime ether adducts, and two members, 2-nonanone and 2-undecanone, were quantified using AEP-labeled external standards. Finally, Chapter 5 concludes with additional demonstrations of click chemistry. We used oximation to ligate linker molecules to fluorophores and gold nanoparticles (AuNPs) to generate a fluorescent nano-entity for breast cancer location and diagnosis. Five homologous linkers, each consisting of a thiol-terminated hydrophobic domain coupled to an aminooxy-terminated PEG-based domain, were prerared using a 6-step synthesis in 7-25% overall yield. The aminooxy end subsequently was reacted with an aldehyde-functionalized cypate fluorophore, and the thiol end was used for attachment to gold nanoparticles. Linker attachment to cypate in this manner was superior to previously investigated amide coupling involving linker amines and cypate carboxylic acid. Collectively, the results from these investigations demonstrates a novel strategy that employs functionalized aminooxy substrates and reagents to first exploit the high yielding and selective click coupling with carbonyl substrates to set the stage for secondary synthetic or analytical operations. Approaches developed in this multifaceted study appear to be applicable to a variety of synthetic problems ranging from those of a purely chemical nature to other impacting biological systems.

A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K727, K733) with the oxime HI-6 and obidoxime in sarin-poisoned rats and mice.

PubMed

Kassa, Jiri; Sepsova, Vendula; Matouskova, Lenka; Horova, Anna; Musilek, Kamil

2015-03-01

The ability of two novel bispyridinium oximes K727 and K733 and currently available oximes (HI-6, obidoxime) to reactivate sarin-inhibited acetylcholinesterase and to reduce acute toxicity of sarin was evaluated. To investigate the reactivating efficacy of the oximes, the rats were administered intramuscularly with atropine and oximes in equitoxic doses corresponding to 5% of their LD50 values at 1 min after the intramuscular administration of sarin at a dose of 24 µg/kg (LD50). The activity of acetylcholinesterase was measured at 60 min after sarin poisoning. The LD50 value of sarin in non-treated and treated mice was assessed using probit-logarithmical analysis of death occurring within 24 h after intramuscular administration of sarin at five different doses. In vivo determined percentage of reactivation of sarin-inhibited rat blood, diaphragm and brain acetylcholinesterase showed that the potency of both novel oximes K727 and K733 to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating efficacy of obidoxime. On the other hand, the oxime HI-6 was found to be the most efficient reactivator of sarin-inhibited acetylcholinesterase. While the oxime HI-6 was able to reduce the acute toxicity of sarin >3 times, both novel oximes and obidoxime decreased the acute toxicity of sarin <2 times. Based on the results, we can conclude that the reactivating and therapeutic efficacy of both novel oximes K727 and K733 is significantly lower compared to the oxime HI-6 and, therefore, they are not suitable for the replacement of the oxime HI-6 for the antidotal treatment of acute sarin poisoning.

Synthesis of two and antibacterial activity of one novel oxime ether derivatives of erythromycin A.

PubMed

Dondas, H A; Yaktubay, N

2003-10-01

The synthesis of novel erythromycin A 9-O-(2-ethenesulfony-ethyl)-oxime and erythromycin A 9-O-(3-oxo-butyl)-oxime from erythromycin A (EA) by the Michael reaction is described and to describe the effects of transformation of ketone in position 9 of EA to an oxime ether. This transformation occurred in a single step without protecting of any functional moiety of erythromycin oxime and zero waste manner in good yield. The antibacterial screen of EA 9-O-(2-ethenesulfony-ethyl)-oxime is also reported.

[Comparison of the effects of BI-6, a new asymmetric bipyridine oxime, with HI-6 oxime and obidoxime in combination with atropine on soman and fosdrine toxicity in mice].

PubMed

Kassa, J

1999-01-01

The therapeutic efficacy of the new asymmetric bispyridinium oxime BI-6 against acute toxicity of the highly toxic organophosphate soman and the organophosphorus insecticide fosdrin by means of affecting the LD50 values of these noxiores substances was compared with the effect of the hitherto most perspective oxime HI-6 and the classic obidoxime always in combination with the identical dose of atropine. At the equimolar level the effect of oxime BI-6 against fosdrin completely equals the effects of both oximes HI-6 and obidoxime. The effect of oxime BI-6 against soman is even more marked than the effect of HI-6 but this difference is not statistically significant. On the other hand, at the equi-effective level, the effect of oxime BI-6 against soman is statistically significantly lower than the effect of HI-6, and against fosdrin it is even lower than the effect of both remaining oximes. The effects of the new oxime BI-6 equal, or slightly exceed the therapeutic effect of HI-6 but at the equimolar level only. At the equi-effective level which respects the toxicity of the oxime and is therefore more important for practical use, it is a therapeutically weaker reactivator of acetylcholinesterase than HI-6.

[Comparison of the reactivating effect of BI-6, a new asymmetrical bispyridinium oxime, with oxime HI-6 and obidoxime on soman-inhibited acetylcholinesterase in the diaphragm and various parts of the brain in rats].

PubMed

Kassa, J; Bajgar, J

1999-08-30

Acute poisoning with the highly toxic organophosphorus agent, soman, is not treated satisfactorily even by the most modern antidotes. In experiments on rats, the reactivating effect of a new asymmetric bispyridinium oxime BI-6 was compared with widely used oximes HI-6 and obidoxime by investigating the changes of soman-inhibited acetylcholinesterase activity in the diaphragm and various parts of the brain in rats up to three hours following soman challenge. Our findings confirm that the new oxime BI-6 is a more effective reactivator of soman-inhibited acetylcholinesterase than obidoxime but not as effective as the oxime HI-6 especially in the peripheral compartment. The new oxime BI-6 is not as effective as HI-6 which seems to have definite advantages over other oximes in the treatment of soman poisoning.

Artificial Enzymes with Thiazolium and Imidazolium Coenzyme Mimics

PubMed Central

Zhao, Huanyu; Foss, Frank W.; Breslow, Ronald

2009-01-01

Hydrophobic thiazolium and imidazolium coenzyme mimics in the presence of modified-polyethylenimine enzyme mimics catalyze the benzoin condensation 2300–3300 times faster than the coenzyme mimics alone. Polycationic enzyme mimics provide not only a hydrophobic binding domain for coenzyme and substrate, but also electrostatic stabilization of anionic species that arise along the reaction pathway of the benzoin condensation. PMID:18763766

Lanthanum Tricyanide-Catalyzed Acyl Silane-Ketone Benzoin Additions and Kinetic Resolution of Resultant α-Silyloxyketones

PubMed Central

Tarr, James C.

2010-01-01

We report the full account of our efforts on the lanthanum tricyanide-catalyzed acyl silane-ketone benzoin reaction. The reaction exhibits a wide scope in both acyl silane (aryl, alkyl) and ketone (aryl-alkyl, alkyl-alkyl, aryl-aryl, alkenyl-alkyl, alkynyl-alkyl) coupling partners. The diastereoselectivity of the reaction has been examined in both cyclic and acyclic systems. Cyclohexanones give products arising from equatorial attack by the acyl silane. The diastereoselectivity of acyl silane addition to acyclic α-hydroxy ketones can be controlled by varying the protecting group to obtain either Felkin-Ahn or chelation control. The resultant α-silyloxyketone products can be resolved with selectivity factors from 10 to 15 by subjecting racemic ketone benzoin products to CBS reduction. PMID:20392127

Nitrite Formation from Hydroxylamine and Oximes by Pseudomonas aeruginosa

PubMed Central

Amarger, Noelle; Alexander, M.

1968-01-01

Nitrite was formed from hydroxylamine and several oximes by intact cells and extracts of Pseudomonas aeruginosa. The activity was induced by the presence of oximes in the culture medium. Nitroalkanes were not intermediates in the conversion of acetaldoxime, acetone oxime, or butanone oxime to nitrite, since nitromethane inhibited the formation of nitrite from the nitro compounds but not from the corresponding oximes. The oxime apparently functions as a constant source of hydroxylamine during growth of the bacterium. Hydroxylamine at low concentration was converted stoichiometrically to nitrite by extracts of the bacterium; high concentrations were inhibitory. Nicotinamide adenine dinucleotide phosphate, oxygen, and other unidentified cofactors were necessary for the reaction. Actively nitrifying extracts possessed no hydroxylamine-cytochrome c reductase activity. Hyponitrite, nitrous oxide, and nitric oxide were not metabolized. PMID:4384968

A Common Mechanism for Resistance to Oxime Reactivation of Acetylcholinesterase Inhibited by Organophosphorus Compounds

DTIC Science & Technology

2013-01-01

application of the Hammett equation with the constants rph in the chemistry of organophosphorus compounds, Russ. Chem. Rev. 38 (1969) 795–811. [13...of oximes and OP compounds and the ability of oximes to reactivate OP- inhibited AChE. Multiple linear regression equations were analyzed using...phosphonate pairs, 21 oxime/ phosphoramidate pairs and 12 oxime/phosphate pairs. The best linear regression equation resulting from multiple regression anal

Site-selective benzoin-type cyclization of unsymmetrical dialdoses catalyzed by N-heterocyclic carbenes for divergent cyclitol synthesis.

PubMed

Kang, Bubwoong; Wang, Yinli; Kuwano, Satoru; Yamaoka, Yousuke; Takasu, Kiyosei; Yamada, Ken-Ichi

2017-04-18

A highly site-selective N-heterocyclic carbene (NHC)-catalyzed benzoin-type cyclization of unsymmetrical dialdoses is developed to enable a divergent cyclitol synthesis. The choice of chiral NHCs and protecting groups affects the site-selectivity. The resulting inososes are converted into epi-, muco- and myo-inositols, and their chiral protected derivatives are formed in good yields.

Stereodivergent Synthesis of Chromanones and Flavanones via Intramolecular Benzoin Reaction.

PubMed

Wen, Genfa; Su, Yingpeng; Zhang, Guoxiang; Lin, Qiqiao; Zhu, Yujin; Zhang, Qianqian; Fang, Xinqiang

2016-08-19

The strategy of stereodivergent reactions on racemic mixtures (stereodivergent RRM) was employed for the first time in intramolecular benzoin reactions and led to the rapid access of chromanones/flavanones with two consecutive stereocenters. The easily separable stereoisomers of the products were obtained with moderate to excellent enantioselectivities in a single step. Catechol type additives proved crucial in achieving the desired diastereo- and enantioselectivities.

Synthesis, spectra and X-ray crystallography of dipyridin-2-ylmethanone oxime and its CuX2(oxime)2 complexes: Thermal, Hirshfeld surface and DFT analysis

NASA Astrophysics Data System (ADS)

Warad, Ismail; Abdoh, Muneer; Al Ali, Anas; Shivalingegowda, Naveen; Kumara, Karthik; Zarrouk, Abdelkader; Lokanath, Neartur Krishnappagowda

2018-02-01

Dipyridin-2-ylmethanone oxime (C11H9N3O), was prepared using di-2-pyridyl ketone. The oxime ligand and its neutral CuX2 (oxime)2 (X = Cl or Br) complexes have been identified with the aid of several spectroscopic techniques such as: IR, EI-MS, EA, UV-visible, TG, 1H-NMR and finally the structure of the free oxime ligand was confirmed by X-ray diffraction studies. The oxime crystallizes in the monoclinic space group P21/c, with cell parameters a = 8.8811 (8) Å, b = 10.6362 (8) Å, c = 11.2050 (8) Å, β = 109.085 (4) º, V = 1000.26 (14) Å3 and Z = 4. The molecular conformation is stabilized by a strong intramolecular Osbnd H⋯N hydrogen bonding between the hydroxyl group of the oxime moiety and the nitrogen of the pyridine ring. Since the oxime structure was solved by XRD, the ligand structure parameters like bond length and angles were compared to the DFT computed one, the UV-visible to TD-SCF and Hirshfeld surface to MEP analysis.

In vitro P-glycoprotein activity does not completely explain in vivo efficacy of novel centrally effective oxime acetylcholinesterase reactivators.

PubMed

Dail, Mary Beth; Meek, Edward Caldwell; Chambers, Howard Wayne; Chambers, Janice Elaine

2018-05-03

Novel-substituted phenoxyalkyl pyridinium oxime acetylcholinesterase (AChE) reactivators (US patent 9,227,937) that showed convincing evidence of penetration into the brains of intact rats were developed by our laboratories. The oximes separated into three groups based on their levels of brain AChE reactivation following exposure of rats to the sarin surrogate nitrophenyl isopropyl methylphosphonate (NIMP). P-glycoprotein (P-gp) is a major blood-brain barrier (BBB) transporter and requires ATP for efflux. To determine if P-gp affinity screening could be used to reduce animal use, we measured in vitro oxime-stimulated ATPase activity to see if the in vivo reactivation efficacies related to the oximes' functions as P-gp substrates. High efficacy oximes were expected to be poor P-gp substrates, thus remaining in the brain longer. The high efficacy oximes (24-35% brain AChE reactivation) were worse P-gp substrates than the low efficacy oximes (0-7% brain AChE reactivation). However, the oxime group with medium in vivo reactivation of 10-17% were even worse P-gp substrates than the high efficacy group so their reactivation ability was not reflected by P-gp export. The results suggest that in vitro P-gp ATPase activity can remove the low efficacy oximes from in vivo testing, but is not sufficient to differentiate between the top two tiers.

40 CFR 721.10262 - Oxime, Me vinyl silane (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxime, Me vinyl silane (generic). 721... Substances § 721.10262 Oxime, Me vinyl silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, Me vinyl silane (PMN P...

40 CFR 721.10262 - Oxime, Me vinyl silane (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxime, Me vinyl silane (generic). 721... Substances § 721.10262 Oxime, Me vinyl silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, Me vinyl silane (PMN P...

Influence of Crosslinking on the Mechanical Properties of High TG Polymers

DTIC Science & Technology

1976-07-01

with UV light has been previously described (48). In brief, benzoin was used as the initiator (0.3 percent), acrylic acid anhydride (AAA) as the labile...1.9 1.0 1.8 0.8 1.7 110 4M (th)x 10 1.0 2.0 1.0 2.0 1.0 2.0 4M- -(E) x 10 0.9 1.2 0.9 1.3 0.7 1.2 1.7 EA: 100 ml Benzoin : 0.4 g 22 Table 3. PEA...L) x 10 4.1 9.0 4.0 10.0 2.4 - - c (wg)x 104 5.7 8.7 3.5 8.4 2.7 - - M-c (E) x 10 1.2 2.1 1.0 2.1 0.8 1.0 1.3 EA: 100 ml Benzoin : 0.4 g Table 4. PEA

Catalytic Enantioselective Aza-Benzoin Reactions of Aldehydes with 2H-Azirines.

PubMed

Peng, Qiupeng; Guo, Donghui; Bie, Jianbo; Wang, Jian

2018-03-26

The unprecedented enantioselective aza-benzoin reaction of aldehydes with 2H-azirines was developed by utilizing a chiral N-heterocyclic carbene as the catalyst. A wide range of corresponding aziridines can be obtained in good yields with high enantioselectivities. The obtained optically active aziridines should be useful in the synthesis of other valuable molecules. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multicatalytic asymmetric synthesis of complex tetrahydrocarbazoles via a Diels-Alder/benzoin reaction sequence.

PubMed

Liu, Yankai; Nappi, Manuel; Escudero-Adán, Eduardo C; Melchiorre, Paolo

2012-03-02

Expanding upon the recently developed aminocatalytic asymmetric indole-2,3-quinodimethane strategy, a straightforward synthesis of structurally and stereochemically complex tetrahydrocarbazoles has been devised. The chemistry's complexity-generating power was further harnessed by designing a multicatalytic, one-pot Diels-Alder/benzoin reaction sequence to stereoselectively access trans-fused tetracyclic indole-based compounds having four stereogenic centers with very high fidelity. © 2012 American Chemical Society

The enzymes with benzil reductase activity conserved from bacteria to mammals.

PubMed

Maruyama, Reiji; Nishizawa, Mikio; Itoi, Yasushi; Ito, Seiji; Inoue, Masami

2002-03-28

The diketone compound, benzil is reduced to (S)-benzoin with living Bacillus cereus cells. Recently, we isolated a gene responsible for benzil reduction, and Escherichia coli cells in which this gene was overexpressed transformed benzil to (S)-benzoin. Although this benzil reductase showed high identity to the short-chain dehydrogenase/reductase (SDR) family, enzymological features were unknown. Here, we demonstrated that many B. cereus strains had benzil reductase activity in vivo, and that the benzil reductases shared 94-100% amino acid identities. Recombinant B. cereus benzil reductase produced optically pure (S)-benzoin with NADPH in vitro, and the ketone group distal to a benzene ring was asymmetrically reduced. B. cereus benzil reductase showed 31% amino acid identity to the yeast open reading frame YIR036C protein and 28-30% to mammalian sepiapterin reductases, sharing the seven residues consensus for the SDR family. We isolated the genes encoding yeast YIR036C protein and gerbil sepiapterin reductase, and both recombinant proteins also reduced benzil to (S)-benzoin in vitro. Green fluorescent protein-tagged B. cereus benzil reductase distributed in the bipolar cytoplasm in B. cereus cells. Asymmetric reduction with B. cereus benzil reductase, yeast YIR036C protein and gerbil sepiapterin reductase will be utilized to produce important chiral compounds.

40 CFR 721.10261 - Oxime, di-Me silane (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN P-09-589...

40 CFR 721.10261 - Oxime, di-Me silane (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN P-09-589...

21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Milbemcyin oxime and lufenuron tablets. 520.1446... oxime and lufenuron tablets. (a) Specifications—(1) Tablets containing: 2.3 milligrams (mg) milbemycin... 230 mg lufenuron, or 23 mg milbemycin oxime and 460 mg lufenuron. (2) Flavored tablets containing: 2.3...

A comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator KR-22934 with the oxime K203 and commonly used oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice.

PubMed

Kassa, Jiri; Karasova, Jana Zdarova; Pavlikova, Ruzena; Musilek, Kamil; Kuca, Kamil; Bajgar, Jiri; Jung, Young-Sik

2011-03-01

The potency of bispyridinium acetylcholinesterase reactivator KR-22934 in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with the oxime K203 and commonly used oximes. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of KR-22934 was slightly higher than the reactivating efficacy of K203 and roughly corresponded to the reactivating efficacy of obidoxime and trimedoxime in blood and diaphragm. On the other hand, the oxime KR-22934 was not able to reactivate tabun-inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied approximately corresponded to their reactivating efficacy. Based on the results, one can conclude that the oxime KR-22934 is not suitable for the replacement of commonly used oximes for the antidotal treatment of tabun poisoning in spite of its potency to reactivate tabun-inhibited acetylcholinesterase in the peripheral compartment (blood, diaphragm).

A comparison of the neuroprotective efficacy of individual oxime (HI-6) and combinations of oximes (HI-6+trimedoxime, HI-6+K203) in soman-poisoned rats.

PubMed

Kassa, Jiri; Karasova, Jana Zdarova; Tesarova, Sandra

2011-07-01

The ability of two combinations of oximes (HI-6+trimedoxime, HI-6+K203) to reduce soman-induced acute neurotoxic signs and symptoms was compared with the neuroprotective efficacy of the oxime HI-6 alone, using a functional observational battery. Soman-induced neurotoxicity and the neuroprotective effects of HI-6 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with soman at a sublethal dose (90 μg/kg intramuscularly, i.m.; 80% of LD₅₀ value) were monitored by the functional observational battery at 24 hours following soman administration. The results indicate that both tested oxime mixtures combined with atropine were able to allow soman-poisoned rats to survive 24 hours following soman challenge, while 4 nontreated soman-poisoned rats and 1 soman-poisoned rat treated with oxime HI-6 alone combined with atropine died within 24 hours following soman poisoning. While the oxime HI-6 alone combined with atropine treatment was able to eliminate a few soman-induced neurotoxic signs and symptoms, both oxime mixtures showed higher neuroprotective efficacy in soman-poisoned rats. Especially, the combination of HI-6 with trimedoxime was able to eliminate most soman-induced neurotoxic signs and symptoms and markedly reduce acute neurotoxicity of soman in rats. Thus, both tested mixtures of oximes combined with atropine were able to increase the neuroprotective effectiveness of antidotal treatment of acute soman poisonings, compared to the individual oxime.

21 CFR 520.1445 - Milbemycin oxime tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Milbemycin oxime tablets. 520.1445 Section 520... tablets. (a) Specifications—(1) Dogs. Each tablet contains 2.3, 5.75, 11.5, or 23.0 milligrams of milbemycin oxime. (2) Cats. Each tablet contains 5.75, 11.5, or 23.0 milligrams of milbemycin oxime. (b...

Solvent-Free Benzoin and Stetter Reactions with a Small Amount of NHC Catalyst in the Liquid or Semisolid State.

PubMed

Ema, Tadashi; Nanjo, Yoshiko; Shiratori, Sho; Terao, Yuta; Kimura, Ryo

2016-11-04

The intermolecular or intramolecular asymmetric benzoin reaction was catalyzed by a small amount of N-heterocyclic carbene (NHC) (0.2-1 mol %) under solvent-free conditions. The solvent-free intramolecular asymmetric Stetter reaction also proceeded efficiently with NHC (0.2-1 mol %). In some cases, even solid-to-solid or solid-to-liquid conversions took place with low catalyst loading (0.2-1 mol %).

Oxidation of Benzoin to Benzil Using Alumina-Supported Active MnO2

NASA Astrophysics Data System (ADS)

Crouch, R. David; Holden, Michael S.; Burger, Jennifer S.

2001-07-01

The use of alumina-supported active MnO2 to oxidize benzoin to benzil is described. The advantages of this reagent include ease of handling and separation from the product and lower toxicity than previously reported supported oxidizing agents. The product is purified by elution through a simple chromatography column consisting of a silica gel-packed Pasteur pipet. Students' yields are comparable to yields from other reported oxidation methods.

Efficient Domino Hydroformylation/Benzoin Condensation: Highly Selective Synthesis of α-Hydroxy Ketones.

PubMed

Dong, Kaiwu; Sang, Rui; Soule, Jean-Francois; Bruneau, Christian; Franke, Robert; Jackstell, Ralf; Beller, Matthias

2015-12-07

An improved domino hydroformylation/benzoin condensation to give α-hydroxy ketones has been developed. Easily available olefins are smoothly converted into the corresponding α-hydroxy ketones in high yields with excellent regioselectivities. Key to success is the use of a specific catalytic system consisting of a rhodium/phosphine complex and the CO2 adduct of an N-heterocyclic carbene. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemoselective N-heterocyclic carbene-catalyzed cross-benzoin reactions: importance of the fused ring in triazolium salts.

PubMed

Langdon, Steven M; Wilde, Myron M D; Thai, Karen; Gravel, Michel

2014-05-28

Morpholinone- and piperidinone-derived triazolium salts are shown to catalyze highly chemoselective cross-benzoin reactions between aliphatic and aromatic aldehydes. The reaction scope includes ortho-, meta-, and para-substituted benzaldehyde derivatives with a range of electron-donating and -withdrawing groups as well as branched and unbranched aliphatic aldehydes. Catalytic loadings as low as 5 mol % give excellent yields in these reactions (up to 99%).

NHC-catalysed benzoin condensation - is it all down to the Breslow intermediate?

PubMed

Rehbein, Julia; Ruser, Stephanie-M; Phan, Jenny

2015-10-01

The Breslow catalytic cycle describing the benzoin condensation promoted by N-heterocyclic carbenes (NHC) as proposed in the late 1950s has since then been tried by generations of physical organic chemists. Emphasis has been laid on proofing the existence of an enaminol like structure (Breslow intermediate) that explains the observed umpolung of an otherwise electrophilic aldehyde. The present study is not focusing on spectroscopic elucidation of a thiazolydene based Breslow intermediate but rather tries to clarify if this key-intermediate is indeed directly linked with the product side of the overall reaction. The here presented EPR-spectroscopic and computational data provide a fundamentally different view on how the benzoin condensation may proceed: a radical pair could be identified as a second key-intermediate that is derived from the Breslow-intermediate via an SET process. These results highlight the close relationship to the Cannizarro reaction and oxidative transformations of aldehydes under NHC catalysis.

CIDEP study on the flash photolysis of benzoin included in β-cyclodextrin

NASA Astrophysics Data System (ADS)

Kitahama, Yasutaka; Murai, Hisao

1996-10-01

The photodissociation reaction of benzoin (Norrish type I) included in a β-cyclodextrin (CD) cavity in the aqueous phase was studied by using time-resolved ESR and Fourier transform ESR methods. The CIDEP (chemically induced dynamic electron polarization) spectra of α-hydroxybenzyl radical and benzoyl radical were carefully investigated in β-CD, in ethanol, in an ethanol/water mixture, and in saturated aqueous solutions. According to these data and the calculations due to an extended Bloch equation, the spin-lattice relaxation time observed in the β-CD system was compared to those in homogeneous solutions. It is concluded that dissociation takes place from the excited triplet state of benzoin and the fragment radicals are easily ejected from the cavity of β-CD to the aqueous phase much faster than the time-resolution (˜ 20 ns) of the present FT-ESR measurement.

Impacts of Different Functional Groups on the Kinetic Rates of α-Amine Ketoximesilanes Hydrolysis in the Preparation of Room Temperature Vulcanized Silicone Rubber.

PubMed

Xu, Huihui; Liu, Zihou; Liu, Qingyang; Bei, Yiling; Zhu, Qingzeng

2018-05-13

α-Amine ketoximesilanes are proven to be effective crosslinkers in the preparation of ketone-oxime one-component room temperature vulcanized (RTV) silicone rubber without the use of toxic metal catalyst. This work aimed to investigate the hydrolysis kinetic of α-amine ketoximesilanes, which is vitally important for the preparation of RTV silicone rubber. Five kinds of α-amine ketoximesilanes, namely α-(N,N-diethyl)aminomethyltri(methylethylketoxime)silane (DEMOS), α-(N,N-di-n-butyl)aminomethyltri(methylethylketoxime)silane (DBMOS), α-(N-n-butyl)aminomethyltri(methylethylketoxime)silane (n-BMOS), α-(N-cyclohexyl)aminomethyltri(methylethylketoxime)silane (CMOS) and α-(β-aminomethyl)aminomethyltri(methylethylketoxime)silane (AEMOS), were successfully obtained and confirmed using Fourier transform infrared spectrometer (FT-IR) and hydrogen-1 nuclear magnetic resonance ( ¹H NMR). Kinetics of hydrolysis reactions were measured by FT-IR and conductivity. Our results illustrated that the kinetic constant rates ranged from 12.2 × 10 −4 s −1 to 7.6 × 10 −4 s −1 , with the decreasing order of DEMOS > n-BMOS > DBMOS > CMOS > AEMOS at the given temperature and humidity. Better performances of thermal stability could be achieved when using the α-amine ketoximesilanes as crosslinkers in the preparation of RTV silicon rubber than that of RTV silicone rubber with the use of methyltri(methylethylketoxime)silane (MOS) as a crosslinker and organic tin as a catalyst.

Oximes: Inhibitors of Human Recombinant Acetylcholinesterase. A Structure-Activity Relationship (SAR) Study

PubMed Central

Sepsova, Vendula; Karasova, Jana Zdarova; Korabecny, Jan; Dolezal, Rafael; Zemek, Filip; Bennion, Brian J.; Kuca, Kamil

2013-01-01

Acetylcholinesterase (AChE) reactivators were developed for the treatment of organophosphate intoxication. Standard care involves the use of anticonvulsants (e.g., diazepam), parasympatolytics (e.g., atropine) and oximes that restore AChE activity. However, oximes also bind to the active site of AChE, simultaneously acting as reversible inhibitors. The goal of the present study is to determine how oxime structure influences the inhibition of human recombinant AChE (hrAChE). Therefore, 24 structurally different oximes were tested and the results compared to the previous eel AChE (EeAChE) experiments. Structural factors that were tested included the number of pyridinium rings, the length and structural features of the linker, and the number and position of the oxime group on the pyridinium ring. PMID:23959117

Oxidation of benzoin catalyzed by oxovanadium(IV) schiff base complexes

PubMed Central

2013-01-01

Background The oxidative transformation of benzoin to benzil has been accomplished by the use of a wide variety of reagents or catalysts and different reaction procedures. The conventional oxidizing agents yielded mainly benzaldehyde or/and benzoic acid and only a trace amount of benzil. The limits of practical utilization of these reagents involves the use of stoichiometric amounts of corrosive acids or toxic metallic reagents, which in turn produce undesirable waste materials and required high reaction temperatures. In recent years, vanadium complexes have attracted much attention for their potential utility as catalysts for various types of reactions. Results Active and selective catalytic systems of new unsymmetrical oxovanadium(IV) Schiff base complexes for the oxidation of benzoin is reported. The Schiff base ligands are derived between 2-aminoethanol and 2-hydroxy-1-naphthaldehyde (H2L1) or 3-ethoxy salicylaldehyde (H2L3); and 2-aminophenol and 3-ethoxysalicylaldehyde (H2L2) or 2-hydroxy-1-naphthaldehyde (H2L4). The unsymmetrical Schiff bases behave as tridentate dibasic ONO donor ligands. Reaction of these Schiff base ligands with oxovanadyl sulphate afforded the mononuclear oxovanadium(IV) complexes (VIVOLx.H2O), which are characterized by various physico-chemical techniques. The catalytic oxidation activities of these complexes for benzoin were evaluated using H2O2 as an oxidant. The best reaction conditions are obtained by considering the effect of solvent, reaction time and temperature. Under the optimized reaction conditions, VOL4 catalyst showed high conversion (>99%) with excellent selectivity to benzil (~100%) in a shorter reaction time compared to the other catalysts considered. Conclusion Four tridentate ONO type Schiff base ligands were synthesized. Complexation of these ligands with vanadyl(IV) sulphate leads to the formation of new oxovanadium(IV) complexes of type VIVOL.H2O. Elemental analyses and spectral data of the free ligands and their oxovanadium(IV) complexes were found to be in good agreement with their structures, indicating high purity of all the compounds. Oxovanadium complexes were screened for the oxidation of benzoin to benzil using H2O2 as oxidant. The effect of time, solvent and temperature were optimized to obtain maximum yield. The catalytic activity results demonstrate that these catalytic systems are both highly active and selective for the oxidation of benzoin under mild reaction conditions. PMID:23294561

Oxidation of benzoin catalyzed by oxovanadium(IV) schiff base complexes.

PubMed

Alsalim, Tahseen A; Hadi, Jabbar S; Ali, Omar N; Abbo, Hanna S; Titinchi, Salam Jj

2013-01-07

The oxidative transformation of benzoin to benzil has been accomplished by the use of a wide variety of reagents or catalysts and different reaction procedures. The conventional oxidizing agents yielded mainly benzaldehyde or/and benzoic acid and only a trace amount of benzil. The limits of practical utilization of these reagents involves the use of stoichiometric amounts of corrosive acids or toxic metallic reagents, which in turn produce undesirable waste materials and required high reaction temperatures.In recent years, vanadium complexes have attracted much attention for their potential utility as catalysts for various types of reactions. Active and selective catalytic systems of new unsymmetrical oxovanadium(IV) Schiff base complexes for the oxidation of benzoin is reported. The Schiff base ligands are derived between 2-aminoethanol and 2-hydroxy-1-naphthaldehyde (H2L1) or 3-ethoxy salicylaldehyde (H2L3); and 2-aminophenol and 3-ethoxysalicylaldehyde (H2L2) or 2-hydroxy-1-naphthaldehyde (H2L4). The unsymmetrical Schiff bases behave as tridentate dibasic ONO donor ligands. Reaction of these Schiff base ligands with oxovanadyl sulphate afforded the mononuclear oxovanadium(IV) complexes (VIVOLx.H2O), which are characterized by various physico-chemical techniques.The catalytic oxidation activities of these complexes for benzoin were evaluated using H2O2 as an oxidant. The best reaction conditions are obtained by considering the effect of solvent, reaction time and temperature. Under the optimized reaction conditions, VOL4 catalyst showed high conversion (>99%) with excellent selectivity to benzil (~100%) in a shorter reaction time compared to the other catalysts considered. Four tridentate ONO type Schiff base ligands were synthesized. Complexation of these ligands with vanadyl(IV) sulphate leads to the formation of new oxovanadium(IV) complexes of type VIVOL.H2O.Elemental analyses and spectral data of the free ligands and their oxovanadium(IV) complexes were found to be in good agreement with their structures, indicating high purity of all the compounds.Oxovanadium complexes were screened for the oxidation of benzoin to benzil using H2O2 as oxidant. The effect of time, solvent and temperature were optimized to obtain maximum yield. The catalytic activity results demonstrate that these catalytic systems are both highly active and selective for the oxidation of benzoin under mild reaction conditions.

A comprehensive evaluation of novel oximes in creation of butyrylcholinesterase-based nerve agent bioscavengers

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

Katalinić, Maja; Maček Hrvat, Nikolina

A well-considered treatment of acute nerve agents poisoning involves the exogenous administration of butyrylcholinesterase (BChE, EC 3.1.1.8) as a stoichiometric bioscavenger efficient in preventing cholinergic crises caused by acetylcholinesterase (AChE, EC 3.1.1.7) inhibition. An additional improvement in medical countermeasures would be to use oximes that could reactivate BChE as well to upgrade bioscavenging from stoichiometric to oxime-assisted catalytic. Therefore, in this paper we investigated the potency of 39 imidazolium and benzimidazolium oximes (36 compounds synthesized for the first time) to be considered as the reactivators specifically designed for reactivation of phosphylated human BChE. Their efficiency in the reactivation of paraoxon-,more » VX-, and tabun-inhibited human BChE, as well as human AChE was tested and compared with the efficiencies of HI-6 and obidoxime, used in medical practice today. A comprehensive analysis was performed for the most promising oximes defining kinetic parameters of reactivation as well as interactions with uninhibited BChE. Furthermore, experimental data were compared with computational studies (docking, QSAR analysis) as a starting point in future oxime structure refinement. Considering the strict criteria set for in vivo applications, we determined the cytotoxicity of lead oximes on two cell lines. Among the tested oxime library, one imidazolium compound was selected for preliminary in vivo antidotal study in mice. The obtained protection in VX poisoning outlines its potential in development oxime-assisted OP-bioscavenging with BChE. - Highlights: • 36 new imidazolium and benzimidazolium oximes were designed and synthesized. • In vitro reactivation kinetics of phosphylated butyrylcholinesterase was studded. • The modes of actions were elucidated by QSAR and docking simulations. • Protection in VX poisoning was 6.3 × LD{sub 50} in in vivo antidotal study in mice. • Imidazolium oxime-assisted catalysis is feasible for OP-bioscavenging with BChE.« less

One-pot, two-step desymmetrization of symmetrical benzils catalyzed by the methylsulfinyl (dimsyl) anion.

PubMed

Ragno, Daniele; Bortolini, Olga; Giovannini, Pier Paolo; Massi, Alessandro; Pacifico, Salvatore; Zaghi, Anna

2014-08-14

An operationally simple one-pot, two-step procedure for the desymmetrization of benzils is herein described. This consists in the chemoselective cross-benzoin reaction of symmetrical benzils with aromatic aldehydes catalyzed by the methyl sulfinyl (dimsyl) anion, followed by microwave-assisted oxidation of the resulting benzoylated benzoins with nitrate, avoiding the costly isolation procedure. Both electron-withdrawing and electron-donating substituents may be accommodated on the aromatic rings of the final unsymmetrical benzil.

Inhibitory Effects of Thai Essential Oils on Potentially Aflatoxigenic Aspergillus parasiticus and Aspergillus flavus.

PubMed

Jantapan, Kittika; Poapolathep, Amnart; Imsilp, Kanjana; Poapolathep, Saranya; Tanhan, Phanwimol; Kumagai, Susumu; Jermnak, Usuma

2017-01-01

　The antiaflatoxigenic and antifungal activities of essential oils (EOs) of finger root (Boesenbergia rotunda (L.) Mansf.), pine (Pinus pinaster), rosewood (Aniba rosaedora), Siam benzoin (Styrax tonkinensis), Thai moringa (Moringa oleifera), and ylang ylang (Cananga odorata) were tested for Aspergillus parasiticus and Aspergillus flavus in potato dextrose broth. Aflatoxin B 1 (AFB 1 ) was extracted from culture using a QuEChERS-based extraction procedure and analyzed with high performance liquid chromatography (HPLC) coupled to a fluorescence detector. EO of pine showed the greatest inhibition of growth and AFB 1 production of A. parasiticus, followed by EOs of rosewood, finger root, Siam benzoin, and ylang ylang. EO of finger root gave the best inhibitory effects on A. flavus, followed by EOs of rosewood, pine, ylang ylang, and Siam benzoin. EO of Thai moringa did not show any significant inhibition of aflatoxigenic fungi. The antiaflatoxigenic activities of EOs correlated with their antifungal activities in the dosedependent manner. Comparison of the application of the five selected EOs in peanut pods by direct and vapor exposure indicated that the AFB 1 production inhibitory effects of the five EOs by direct exposure were faster and more effective than by vapor exposure. EO of finger root showed the best inhibition of AFB 1 production of A. flavus in peanut pods by direct exposure, followed by EOs of pine, rosewood, ylang ylang, and Siam benzoin.

Indirubin-3'-oxime impairs mitochondrial oxidative phosphorylation and prevents mitochondrial permeability transition induction.

PubMed

Varela, Ana T; Gomes, Ana P; Simões, Anabela M; Teodoro, João S; Duarte, Filipe V; Rolo, Anabela P; Palmeira, Carlos M

2008-12-01

Indirubin, a red colored 3,2'-bisindole isomer, is a component of Indigo naturalis and is an active ingredient used in traditional Chinese medicine for the treatment of chronic diseases. The family of indirubin derivatives, such as indirubin-3'-oxime, has been suggested for various therapeutic indications. However, potential toxic interactions such as indirubin effects on mitochondrial bioenergetics are still unknown. This study evaluated the action of indirubin-3'-oxime on the function of isolated rat liver mitochondria contributing to a better understanding of the biochemical mechanisms underlying the multiple effects of indirubin. Indirubin-3'-oxime incubated with isolated rat liver mitochondria, at concentrations above 10microM, significantly depresses the phosphorylation efficiency of mitochondria as inferred from the decrease in the respiratory control and ADP/O ratios, the perturbations in mitochondrial membrane potential and in the phosphorylative cycle induced by ADP. Furthermore, indirubin-3'-oxime at up to 25microM stimulates the rate of state 4 respiration and inhibits state 3 respiration. The increased lag phase of repolarization was associated with a direct inhibition of the mitochondrial ATPase. Indirubin-3'-oxime significantly inhibited the activity of complex II and IV thus explaining the decreased FCCP-stimulated mitochondrial respiration. Mitochondria pre-incubated with indirubin-3'-oxime exhibits decreased susceptibility to calcium-induced mitochondrial permeability transition. This work shows for the first time multiple effects of indirubin-3'-oxime on mitochondrial bioenergetics thus indicating a potential mechanism for indirubin-3'-oxime effects on cell function.

Indirubin-3'-oxime impairs mitochondrial oxidative phosphorylation and prevents mitochondrial permeability transition induction

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

Varela, Ana T.; Gomes, Ana P.; Simoes, Anabela M.

2008-12-01

Indirubin, a red colored 3,2'-bisindole isomer, is a component of Indigo naturalis and is an active ingredient used in traditional Chinese medicine for the treatment of chronic diseases. The family of indirubin derivatives, such as indirubin-3'-oxime, has been suggested for various therapeutic indications. However, potential toxic interactions such as indirubin effects on mitochondrial bioenergetics are still unknown. This study evaluated the action of indirubin-3'-oxime on the function of isolated rat liver mitochondria contributing to a better understanding of the biochemical mechanisms underlying the multiple effects of indirubin. Indirubin-3'-oxime incubated with isolated rat liver mitochondria, at concentrations above 10{mu}M, significantly depressesmore » the phosphorylation efficiency of mitochondria as inferred from the decrease in the respiratory control and ADP/O ratios, the perturbations in mitochondrial membrane potential and in the phosphorylative cycle induced by ADP. Furthermore, indirubin-3'-oxime at up to 25{mu}M stimulates the rate of state 4 respiration and inhibits state 3 respiration. The increased lag phase of repolarization was associated with a direct inhibition of the mitochondrial ATPase. Indirubin-3'-oxime significantly inhibited the activity of complex II and IV thus explaining the decreased FCCP-stimulated mitochondrial respiration. Mitochondria pre-incubated with indirubin-3'-oxime exhibits decreased susceptibility to calcium-induced mitochondrial permeability transition. This work shows for the first time multiple effects of indirubin-3'-oxime on mitochondrial bioenergetics thus indicating a potential mechanism for indirubin-3'-oxime effects on cell function.« less

40 CFR 721.6660 - Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime...

Code of Federal Regulations, 2014 CFR

2014-07-01

...-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime-blocked (generic name). 721.6660 Section 721.6660... Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime-blocked..., acetone oxime-blocked (PMN P-88-1658) is subject to reporting under this section for the significant new...

40 CFR 721.6660 - Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime...

Code of Federal Regulations, 2013 CFR

2013-07-01

...-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime-blocked (generic name). 721.6660 Section 721.6660... Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime-blocked..., acetone oxime-blocked (PMN P-88-1658) is subject to reporting under this section for the significant new...

40 CFR 721.6660 - Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime...

Code of Federal Regulations, 2012 CFR

2012-07-01

...-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime-blocked (generic name). 721.6660 Section 721.6660... Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime-blocked..., acetone oxime-blocked (PMN P-88-1658) is subject to reporting under this section for the significant new...

Recent advances in evaluation of oxime efficacy in nerve agent poisoning by in vitro analysis.

PubMed

Worek, F; Eyer, P; Aurbek, N; Szinicz, L; Thiermann, H

2007-03-01

The availability of highly toxic organophosphorus (OP) warfare agents (nerve agents) underlines the necessity for an effective medical treatment. Acute OP toxicity is primarily caused by inhibition of acetylcholinesterase (AChE). Reactivators (oximes) of inhibited AChE are a mainstay of treatment, however, the commercially available compounds, obidoxime and pralidoxime, are considered to be rather ineffective against various nerve agents, e.g. soman and cyclosarin. This led to the synthesis and investigation of numerous oximes in the past decades. Reactivation of OP-inhibited AChE is considered to be the most important reaction of oximes. Clinical data from studies with pesticide-poisoned patients support the assumption that the various reactions between AChE, OP and oxime, i.e. inhibition, reactivation and aging, can be investigated in vitro with human AChE. In contrast to animal experiments such in vitro studies with human tissue enable the evaluation of oxime efficacy without being affected by species differences. In the past few years numerous in vitro studies were performed by different groups with a large number of oximes and methods were developed for extrapolating in vitro data to different scenarios of human nerve agent poisoning. The present status in the evaluation of new oximes as antidotes against nerve agent poisoning will be discussed.

Novel oxime based flavanone, naringin-oxime: synthesis, characterization and screening for antioxidant activity.

PubMed

Ozyürek, Mustafa; Akpınar, Damla; Bener, Mustafa; Türkkan, Baki; Güçlü, Kubilay; Apak, Reşat

2014-04-05

Recent interest in polyphenolic antioxidants due to their involvement in health benefits has led to the investigation of new polyphenolic compounds with enhanced antioxidant activity. Naringin (4',5,7-trihydroxyflavanone-7-β-l-rhamnoglucoside-(1,2)-α-d-glucopyranoside) is one of the major flavanones in citrus and grapefruit. The present study aimed to synthesize naringin oxime from naringin and to evaluate its antioxidant and anticancer potential using in vitro assay system. The structure of the synthesized compound, naringin oxime, was elucidated by FT-IR, (1)H NMR, elemental analysis and UV-vis spectroscopy. Antioxidant capacity of naringin oxime, as measured by the cupric reducing antioxidant capacity (CUPRAC) method, was found to be higher than that of the parent compound naringin. Other parameters of antioxidant activity (scavenging effects on OH, O2(-), and H2O2) of naringin and naringin oxime were also determined. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A new photostabilizer: Hydrogenated benzoin derivatives

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

Yamaguchi, K.; Ohkatsu, Y.

1993-12-31

It is found that synergistic effects based on combined use of HALS (hindered Amine Light Stabilizers) with phenolic antioxidants consist of the action of HALS as hydrogen donor to quinones, derived from the phenol in autoxidation, excited by uv light. The finding has been realized as a new photostabilizer of hydrogenated benzoin derivatives. They are generally characterized by multifunctions. The o,o`-dihydroxyl-substituted derivatives inter alia extend the life of a phenolic antioxidant co-used, as hydrogen donor, as well as ultimately act as uv absorber.

Biosynthesis of the Cyanogenic Glucosides Linamarin and Lotaustralin in Cassava: Isolation, Biochemical Characterization, and Expression Pattern of CYP71E7, the Oxime-Metabolizing Cytochrome P450 Enzyme1[OA

PubMed Central

Jørgensen, Kirsten; Morant, Anne Vinther; Morant, Marc; Jensen, Niels Bjerg; Olsen, Carl Erik; Kannangara, Rubini; Motawia, Mohammed Saddik; Møller, Birger Lindberg; Bak, Søren

2011-01-01

Cassava (Manihot esculenta) is a eudicotyledonous plant that produces the valine- and isoleucine-derived cyanogenic glucosides linamarin and lotaustralin with the corresponding oximes and cyanohydrins as key intermediates. CYP79 enzymes catalyzing amino acid-to-oxime conversion in cyanogenic glucoside biosynthesis are known from several plants including cassava. The enzyme system converting oxime into cyanohydrin has previously only been identified in the monocotyledonous plant great millet (Sorghum bicolor). Using this great millet CYP71E1 sequence as a query in a Basic Local Alignment Search Tool-p search, a putative functional homolog that exhibited an approximately 50% amino acid sequence identity was found in cassava. The corresponding full-length cDNA clone was obtained from a plasmid library prepared from cassava shoot tips and was assigned CYP71E7. Heterologous expression of CYP71E7 in yeast afforded microsomes converting 2-methylpropanal oxime (valine-derived oxime) and 2-methylbutanal oxime (isoleucine-derived oxime) to the corresponding cyanohydrins, which dissociate into acetone and 2-butanone, respectively, and hydrogen cyanide. The volatile ketones were detected as 2.4-dinitrophenylhydrazone derivatives by liquid chromatography-mass spectrometry. A KS of approximately 0.9 μm was determined for 2-methylbutanal oxime based on substrate-binding spectra. CYP71E7 exhibits low specificity for the side chain of the substrate and catalyzes the conversion of aliphatic and aromatic oximes with turnovers of approximately 21, 17, 8, and 1 min−1 for the oximes derived from valine, isoleucine, tyrosine, and phenylalanine, respectively. A second paralog of CYP71E7 was identified by database searches and showed approximately 90% amino acid sequence identity. In tube in situ polymerase chain reaction showed that in nearly unfolded leaves, the CYP71E7 paralogs are preferentially expressed in specific cells in the endodermis and in most cells in the first cortex cell layer. In fully unfolded leaves, the expression is pronounced in the cortex cell layer just beside the epidermis and in specific cells in the vascular tissue cortex cells. Thus, the transcripts of the CYP71E7 paralogs colocalize with CYP79D1 and CYP79D2. We conclude that CYP71E7 is the oxime-metabolizing enzyme in cyanogenic glucoside biosynthesis in cassava. PMID:21045121

Tertiary Oximes on Brain Acetylcholinesterase and Central Excitatory Effects of Nerve Agents

DTIC Science & Technology

2012-01-01

5 test doses of the oxime. Animals were euthanized 45 min after oxime treatment when blood and target tissues were collected. AChE activity was...the ability of MINA and DHAP to block or terminate nerve agent-induced electroencephalographic (EEG) seizure activity was evaluated. Animals...instrumented to record brain EEG activity were challenged with a seizure-inducing dose (2.0 x LD50) of GB, GF, or VX, and oxime was administered one min

A case of Z/E-isomers elution order inversion caused by cosolvent percentage change in supercritical fluid chromatography.

PubMed

Pokrovskiy, Oleg I; Ustinovich, Konstantin B; Usovich, Oleg I; Parenago, Olga O; Lunin, Valeriy V; Ovchinnikov, Denis V; Kosyakov, Dmitry S

2017-01-06

A case of elution order inversion caused by cosolvent percentage change in supercritical fluid chromatography was observed and investigated in some detail. Z- and E-isomers of phenylisobutylketone oxime experience an elution order reversal on most columns if the mobile phase consists of CO 2 and alcohol. At lower percentages of alcohol Z-oxime is retained less, somewhere at 2-5% coelution occurs and at larger cosolvent volume elution order reverses - Z-oxime is eluted later than E-oxime. We suppose inversion with CO 2 -ROH phases happens due to a shift in balance between two main interactions governing retention. At low ROH percentages stationary phase surface is only slightly covered by ROH molecules so oximes primarily interact with adsorption sites via hydrogen bond formation. Due to intramolecular sterical hindrance Z-oxime is less able to form hydrogen bonds and consequently is eluted first. At higher percentages alcohols occupy most of strong hydrogen bonding sites on silica surface thus leaving non-specific electrostatic interactions predominantly responsible for Z/E selectivity. Z-oxime has a much larger dipole moment than E-oxime and at these conditions it is eluted later. Additional experimental data with CO 2 -CH 3 CN, hexane-iPrOH and CHF 3 -ROH mobile phases supporting this explanation are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

A rapid, convenient, solventless green approach for the synthesis of oximes using grindstone chemistry.

PubMed

Saikia, Lakhinath; Baruah, Jejiron Maheswari; Thakur, Ashim Jyoti

2011-10-04

Synthesis of oximes is an important reaction in organic chemistry, because these versatile oximes are used for protection, purification, and characterization of carbonyl compounds. Nitriles, amides via Beckmann rearrangement, nitro compounds, nitrones, amines, and azaheterocycles can be synthesised from oximes. They also find applications for selective α-activation. In inorganic chemistry, oximes act as a versatile ligand.Several procedures for the preparation of oximes exist, but, most of them have not addressed the green chemistry issue. They are associated with generation of pollutants, requirement of high reaction temperature, low yields, lack of a generalized procedure, etc. Hence, there is a demand for developing an efficient, convenient, and non-polluting or less polluting alternative method for the preparation of oximes. In this context, bismuth compounds are very useful as they are cheap in general, commercially available, air stable crystalline solids, safe, and non-toxic, hence easy to handle. Carbonyl compounds (aliphatic, heterocyclic, and aromatic) were converted into the corresponding oximes in excellent yields by simply grinding the reactants at room temperature without using any solvent in the presence of Bi2O3. Most importantly, this method minimizes waste disposal problems, provides a simple yet efficient example of unconventional methodology and requires short time. We have developed a novel, quick, environmentally safe, and clean synthesis of aldoximes and ketoximes under solvent-free grinding condition.

Photogeneration of refractive-index patterns in doped polyimide films.

PubMed

Chakravorty, K K

1993-05-01

A photosensitive benzophenone tetracarboxylic dianhyride-alkylated diamine polyimide formulation has been evaluated for application in an optical interconnection area. The refractive-index patterns in this material were optically recorded by UV-assisted photodoping of sensitizers. The polyimide films were selectively doped with benzoin-type photosensitizers such as benzildimethylketal and benzoin ethyl ether, which cause a decrease in the refractive index. High-dose UV irradiation that causes cross linking of the polyimide chains was also employed for augmenting the refractive-index difference to 0.017 between the doped and undoped regions. Refractive-index variations and lightguiding properties were investigated as a function of doping concentrations and other processing conditions. The author utilized this technique for the fabrication of embedded polyimide channel waveguides. The two photosensitizers have different effects on the waveguiding characteristics of the polyimide films. Losses for benzoin ethyl ether remained low whereas doping with benzildimethylketal caused significant increase in the waveguiding loss at high doping concentrations. Near-field imaging of the output from such waveguides shows good confinement of 815-nm light.

Cross-benzoin and Stetter-type reactions mediated by KOtBu-DMF via an electron-transfer process.

PubMed

Ragno, Daniele; Zaghi, Anna; Di Carmine, Graziano; Giovannini, Pier Paolo; Bortolini, Olga; Fogagnolo, Marco; Molinari, Alessandra; Venturini, Alessandro; Massi, Alessandro

2016-10-18

The condensation of aromatic α-diketones (benzils) with aromatic aldehydes (benzoin-type reaction) and chalcones (Stetter-type reaction) in DMF in the presence of catalytic (25 mol%) KOtBu is reported. Both types of umpolung processes proceed with good efficiency and complete chemoselectivity. On the basis of spectroscopic evidence (MS analysis) of plausible intermediates and literature reports, the occurrence of different ionic pathways have been evaluated to elucidate the mechanism of a model cross-benzoin-like reaction along with a radical route initiated by an electron-transfer process to benzil from the carbamoyl anion derived from DMF. This mechanistic investigation has culminated in a different proposal, supported by calculations and a trapping experiment, based on double electron-transfer to benzil with formation of the corresponding enediolate anion as the key reactive intermediate. A mechanistic comparison between the activation modes of benzils in KOtBu-DMF and KOtBu-DMSO systems is also described.

Benzaldehyde lyase, a novel thiamine PPi-requiring enzyme, from Pseudomonas fluorescens biovar I.

PubMed Central

González, B; Vicuña, R

1989-01-01

Pseudomonas fluorescens biovar I can grow on benzoin as the sole carbon and energy source. This ability is due to benzaldehyde lyase, a new type of enzyme that irreversibly cleaves the acyloin linkage of benzoin, producing two molecules of benzaldehyde. Benzaldehyde lyase was purified 70-fold and found to require catalytic amounts of thiamine PPi (TPP) and a divalent cation as cofactors. Optimal activity was obtained with a 1.0 mM concentration of Mn2+, Mg2+, or Ca2+. Gel permeation chromatography indicated a native molecular weight of 80,000, whereas the enzyme migrated in sodium dodecyl sulfate-containing polyacrylamide gels as a single polypeptide with a molecular weight of 53,000. Benzaldehyde lyase is highly specific; of a variety of structurally related compounds tested, only benzoin and anisoin (4,4'-dimethoxybenzoin) acted as substrates, their apparent Kms being 9.0 x 10(-3) and 3.25 x 10(-2) mM, respectively. A catalytic mechanism for the enzyme is proposed. Images PMID:2496105

Photogeneration of refractive-index patterns in doped polyimide films

NASA Astrophysics Data System (ADS)

Chakravorty, K. K.

1993-05-01

A photosensitive benzophenone tetracarboxylic dianhyride-alkylated diamine polyimide formulation has been evaluated for application in an optical interconnection area. The refractive-index patterns in this material were optically recorded by UV-assisted photodoping of sensitizers. The polyimide films were selectively doped with benzoin-type photosensitizers such as benzildimethylketal and benzoin ethyl ether, which cause a decrease in the refractive index. High-dose UV irradiation that causes cross linking of the polyimide chains was also employed for augmenting the refractive-index difference to 0.017 between the doped and undoped regions. Refractive-index variations and lightguiding properties were investigated as a function of doping concentrations and other processing conditions. The author utilized this technique for the fabrication of embedded polyimide channel waveguides. The two photosensitizers have different effects on the waveguiding characteristics of the polyimide films. Losses for benzoin ethyl ether remained low whereas doping with benzildimethylketal caused significant increase in the waveguiding loss at high doping concentrations. Near-field imaging of the output from such waveguides shows good confinement of 815-nm light.

Spectroscopic and electrochemical characterization of some Schiff base metal complexes containing benzoin moiety

NASA Astrophysics Data System (ADS)

El-Shahawi, M. S.; Al-Jahdali, M. S.; Bashammakh, A. S.; Al-Sibaai, A. A.; Nassef, H. M.

2013-09-01

The ligation behavior of bis-benzoin ethylenediamine (B2ED) and benzoin thiosemicarbazone (BTS) Schiff bases towards Ru3+, Rh3+, Pd2+, Ni2+ and Cu2+ were determined. The bond length of M-N and spectrochemical parameters (10Dq, β, B and LFSE) of the complexes were evaluated. The redox characteristics of selected complexes were explored by cyclic voltammetry (CV) at Pt working electrode in non aqueous solvents. Au mesh (100 w/in.) optically transparent thin layer electrode (OTTLE) was also used for recording thin layer CV for selected Ru complex. Oxidation of some complexes occurs in a consecutive chemical reaction of an EC type mechanism. The characteristics of electron transfer process of the couples M2+/M3+ and M3+/M4+ (M = Ru3+, Rh3+) and the stability of the complexes towards oxidation and/or reduction were assigned. The nature of the electroactive species and reduction mechanism of selected electrode couples were assigned.

Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates.

PubMed

Chambers, Janice E; Meek, Edward C; Chambers, Howard W

2016-06-01

Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood-brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have developed novel substituted phenoxyalkyl pyridinium oximes that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, treatment of rats with these novel oximes is associated with attenuation of seizure-like behavior compared to rats treated with 2-PAM, providing additional evidence that the oximes penetrate the blood-brain barrier. Further, some of the oximes provided 24-h survival superior to 2-PAM, and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the conclusion that these oximes penetrate the brain. © 2016 New York Academy of Sciences.

Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates

PubMed Central

Chambers, Janice E.; Meek, Edward C.; Chambers, Howard W.

2016-01-01

Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood–brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have invented novel substituted phenoxyalkyl pyridinium oximes (U.S. Patent 9,227,937 B2) that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, these novel oximes also showed an attenuation of seizure-like behavior compared to rats treated with 2-PAM, giving additional evidence of the ability of these oximes to penetrate the blood–brain barrier. Further, some of these oximes provided 24-hour survival superior to 2-PAM and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the concept of these life-saving oximes penetrating the brain. PMID:27153507

Chiral micellar electrokinetic chromatography-atmospheric pressure photoionization of benzoin derivatives using mixed molecular micelles.

PubMed

He, Jun; Shamsi, Shahab A

2011-05-01

In the present work we report, for the first time, the successful on-line coupling of chiral MEKC (CMEKC) to atmospheric pressure photoionization MS (APPI-MS). Four structurally similar neutral test solutes (e.g. benzoin (BNZ) derivatives) were successfully ionized by APPI-MS. The mass spectra in the positive ion mode showed that the protonated molecular ions of BNZs are not the most abundant fragment ions. Simultaneous enantioseparation by CMEKC and on-line APPI-MS detection of four photoinitiators, hydrobenzoin, BNZ, benzoin methyl ether, benzoin ethyl ether, were achieved using an optimized molar ratio of mixed molecular micelle of two polymeric chiral surfactants (polysodium N-undecenoxy carbonyl-L-leucinate and polysodium N-undecenoyl-L,L-leucylvalinate). The CMEKC conditions, such as voltage, chiral polymeric surfactant concentration, buffer pH, and BGE concentration, were optimized using a multivariate central composite design (CCD). The sheath liquid composition (involving %v/v methanol, dopant concentration, electrolyte additive concentration, and flow rate) and spray chamber parameters (drying gas flow rate, drying gas temperature, and vaporizer temperature) were also optimized with CCD. Models built based on the CCD results and response surface method were used to analyze the interactions between factors and their effects on the responses. The final overall optimum conditions for CMEKC-APPI-MS were also predicted and found in agreement with the experimentally optimized parameters. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acquisition of a Laser Scanning Confocal Microscope to Examine CNS Activity of Antidotal Oximes and to Enhance Undergraduate Research Training Across the Sciences

DTIC Science & Technology

2016-07-15

Activity of Antidotal Oximes and to Enhance Undergraduate Research Training Across the Sciences The views, opinions and/or findings contained in this...to Examine CNS Activity of Antidotal Oximes and to Enhance Undergraduate Research Training Across the Sciences Report Title The project utilized...examining the ability of antidotal oximes to rescue organophosphate (OP)-induced CNS toxicity and training across the sciences and social sciences at

Efficacy of novel phenoxyalkyl pyridinium oximes as brain-penetrating reactivators of cholinesterase inhibited by surrogates of sarin and VX.

PubMed

Chambers, Janice E; Chambers, Howard W; Funck, Kristen E; Meek, Edward C; Pringle, Ronald B; Ross, Matthew K

2016-11-25

Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937 B2) with the goal of identifying reactivators effective in crossing the blood-brain barrier. The first 35 of the series were found to have similar in vitro efficacy as reactivators of ChE inhibited by a sarin surrogate (phthalimidyl isopropyl methylphosphonate, PIMP) or a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP) in bovine brain preparations as previously observed in rat brain preparations. A number of these novel oximes have shown the ability to decrease the level of ChE inhibition in the brains of rats treated with a high sublethal dosage of either a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) or the VX surrogate NEMP. Levels of reactivation at 2 h after oxime administration were up to 35% while the currently approved therapeutic, 2-PAM, yielded no reduction in brain ChE inhibition. In addition, there was evidence of attenuation of seizure-like behavior with several of the more effective novel oximes, but not 2-PAM. Therefore these novel oximes have demonstrated an ability to reactivate inhibited ChE in brain preparations from two species and in vivo data support their ability to enter the brain and provide a therapeutic action. These novel oximes have the potential to be developed into improved antidotes for nerve agent therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bridged bicyclic systems as acetylcholinesterase reactivators and pretreatment drugs. Annual report, 15 July 1988-14 July 1989

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

Moriarty, R.M.

1990-03-30

During the past year a large number substituted carbamates, thiocarbamates of various bridged aza bicyclic oximes and their methiodides and meth chlorides have been synthesized. Among these are: (i) O-(N-Substituted carbamoyl)-3-tropinone oxime methiodides and methchlorides, (ii) 0-(N-Substituted carbamoyl)-6-cyano trop-3-ene-2-one oxime methiodides, (iii) O-N-(2`,3`,4`, 6`-Tetra-0-acetyl- b-D-glucopyranosyl thiocarbamoyl)-3-tropinone oxime and its methiodide. Synthesis of 1,6-bis-N`,N`-dimethyl- 3`-oximino-0-carbamoyl tropanonium-N-y1 hexane diiodide and 2,5- bis-(N`N`-dimethyl- 3`-oximino-0-carbamoyl tropanonium-N-yl)-toluene diiodide have been achieved. From phencyclidine a series 4-phenyl-4-0-(N-substituted carbamoyl)-4`-piperidone oxime-1`-yl-1-methyl piperidone methiodides have been synthesized. Syntheses of 0-(N-substituted carbamoyl)-3-exo-dimethyl aminomethyl2-norbornone oximes and their methiodides have been accomplished.

Oxime-Induced Reactivation of Carboxylesterase Inhibited by Organophosphorus Compounds

DTIC Science & Technology

1993-05-13

detoxication enzyme for OP compounds (Maxwell, 1992a), when in the presence of an uncharged oxime, becomes even more effective because it is easily...Wolring, 1984). Therefore, oxime-induced reactivation of OP-inhibited CaE for protection by enhancement of OP detoxication occurs at approximately the

Dynamic kinetic asymmetric cross-benzoin additions of β-stereogenic α-keto esters.

PubMed

Goodman, C Guy; Johnson, Jeffrey S

2014-10-22

The dynamic kinetic resolution of β-halo α-keto esters via an asymmetric cross-benzoin reaction is described. A chiral N-heterocyclic carbene catalyzes the umpolung addition of aldehydes to racemic α-keto esters. The resulting fully substituted β-halo glycolic ester products are obtained with high levels of enantio- and diastereocontrol. The high chemoselectivity observed is a result of greater electrophilicity of the α-keto ester toward the Breslow intermediate. The reaction products are shown to undergo highly diastereoselective substrate-controlled reduction to give highly functionalized stereotriads.

Dynamic Kinetic Asymmetric Cross-Benzoin Additions of β-Stereogenic α-Keto Esters

PubMed Central

2015-01-01

The dynamic kinetic resolution of β-halo α-keto esters via an asymmetric cross-benzoin reaction is described. A chiral N-heterocyclic carbene catalyzes the umpolung addition of aldehydes to racemic α-keto esters. The resulting fully substituted β-halo glycolic ester products are obtained with high levels of enantio- and diastereocontrol. The high chemoselectivity observed is a result of greater electrophilicity of the α-keto ester toward the Breslow intermediate. The reaction products are shown to undergo highly diastereoselective substrate-controlled reduction to give highly functionalized stereotriads. PMID:25299730

Glycoconjugate Oxime Formation Catalyzed at Neutral pH: Mechanistic Insights and Applications of 1,4-Diaminobenzene as a Superior Catalyst for Complex Carbohydrates.

PubMed

Østergaard, Mads; Christensen, Niels Johan; Hjuler, Christian T; Jensen, Knud J; Thygesen, Mikkel B

2018-04-18

The reaction of unprotected carbohydrates with aminooxy reagents to provide oximes is a key method for the construction of glycoconjugates. Aniline and derivatives serve as organocatalysts for the formation of oximes from simple aldehydes, and we have previously reported that aniline also catalyzes the formation of oximes from the more complex aldehydes, carbohydrates. Here, we present a comprehensive study of the effect of aniline analogues on the formation of carbohydrate oximes and related glycoconjugates depending on organocatalyst structure, pH, nucleophile, and carbohydrate, covering more than 150 different reaction conditions. The observed superiority of the 1,4-diaminobenzene (PDA) catalyst at neutral pH is rationalized by NMR analyses and DFT studies of reaction intermediates. Carbohydrate oxime formation at pH 7 is demonstrated by the formation of a bioactive glycoconjugate from a labile, decorated octasaccharide originating from exopolysaccharides of the soil bacterium Mesorhizobium loti. This study of glycoconjugate formation includes the first direct comparison of aniline-catalyzed reaction rates and equilibrium constants for different classes of nucleophiles, including primary oxyamines, secondary N-alkyl oxyamines, as well as aryl and arylsulfonyl hydrazides. We identified 1,4-diaminobenzene as a superior catalyst for the construction of oxime-linked glycoconjugates under mild conditions.

The Oxime Portmanteau Motif: Released Heteroradicals Undergo Incisive EPR Interrogation and Deliver Diverse Heterocycles

PubMed Central

2014-01-01

Conspectus Selective syntheses are now available for compounds of many classes, based on C-centered radicals, exploiting a diverse range of mechanisms. The prospect for chemistry based around N- and O-centered radicals is probably more favorable because of the importance of heterocycles as biologically active materials. Heteroradical chemistry is still comparatively underdeveloped due to the need for safe and easy ways of generating them. Oxime esters appeared promising candidates to meet this need because literature reports and our EPR spectroscopic examinations showed they readily dissociated on photolysis with production of a pair of N- and O-centered radicals. It soon became apparent that a whole suite of benign oxime-containing molecules could be pressed into service. The bimodality of the oxime motif meant that by suitable choice of functionality the reactions could be directed to yield selectively products from either the N-centered radicals or from the O-centered radicals. We found that on one hand photolyses of acetophenone oxime esters of carboxylic acids yielded alicyclics. On the other hand, aromatic and heteroaromatic acyl oximes (as well as dioxime oxalates) afforded good yields of phenanthridines and related heterocycles. Easily prepared oxime oxalate amides released carbamoyl radicals, and pleasingly, β-lactams were thereby obtained. Oxime carbonates and oxime carbamates, available via our novel 1,1'-carbonyldiimidazole (CDI)-based preparations, were accessible alternatives for iminyl radicals and hence for phenanthridine preparations. In their second modes, these compounds proved their value as precursors for exotic alkoxycarbonyloxyl and carbamoyloxyl radicals. Microwave-assistance was shown to be a particularly convenient procedure with O-phenyl oxime ethers. The iminyl radicals generated from such precursors with alkene, alkyne, and aromatic acceptor substituents furnished pyrrole, quinoline, phenanthridine, benzonaphthiridine, indolopyridine, and other systems. Microwave irradiations with 2-(aminoaryl)alkanone O-phenyl oximes enabled either dihydroquinazolines or quinazolines to be obtained in very good yields. The fine quality of the EPR spectra, acquired during photolyses of all the O-carbonyl oxime types, marked this as an important complement to existing ways of obtaining such spectra in solution. Quantifications enabled SARs to be obtained for key reaction types of N- and O-centered radicals, thus putting mechanistic chemistry in this area on a much firmer footing. Surprises included the inverse gem-dimethyl effect in 5-exo-cyclizations of iminyls and the interplay of spiro- with ortho-cyclization onto aromatics. Insights into unusual 4-exo-cyclizations of carbamoyl radicals showed the process to be more viable than pent-4-enyl 4-exo-ring closure. Another surprise was the magnitude of the difference in CO2 loss rate from alkoxycarbonyloxyl radicals as compared with acyloxyl radicals. Their rapid 5-exo-cyclization was charted, as was their preferred spiro-cyclization onto aromatics. The first evidence that N-monosubstituted carbamoyloxyls had finite lifetimes was also forthcoming. It is evident that oxime derivatives have excellent credentials as reagents for radical generation and that there is ample room to extend their applications to additional radical types and for further heterocycle syntheses. There is also clear scope for the development of preparative procedures based around the alkoxyl and aminyl radicals that emerge downstream from oxime carbonate and oxime carbamate dissociations. PMID:24654991

A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides

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

Wilhelm, Christina M., E-mail: wilhelmc@battelle.org; Snider, Thomas H., E-mail: snidert@battelle.org; Babin, Michael C., E-mail: babinm@battelle.org

The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection atmore » the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl{sub 2}, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. - Highlights: • First comprehensive evaluation of leading AChE oxime reactivators • All oximes are compared against current U.S. therapy 2-PAM Cl. • Relative therapeutic oxime efficacies against OP CWNA and pesticides • Contribution to more effective antidotes for civilian and military populations.« less

Nitrogen-containing ecdysteroid derivatives vs. multi-drug resistance in cancer: Preparation and antitumor activity of oximes, oxime ethers and a lactam.

PubMed

Vágvölgyi, Máté; Martins, Ana; Kulmány, Ágnes; Zupkó, István; Gáti, Tamás; Simon, András; Tóth, Gábor; Hunyadi, Attila

2018-01-20

Multidrug resistance is a widespread problem among various diseases and cancer is no exception. We had previously described the chemo-sensitizing activity of ecdysteroid derivatives with low polarity on drug susceptible and multi-drug resistant (MDR) cancer cells. We have also shown that these molecules have a marked selectivity towards the MDR cells. Recent studies on the oximation of various steroid derivatives indicated remarkable increase in their antitumor activity, but there is no related bioactivity data on ecdysteroid oximes. In our present study, 13 novel ecdysteroid derivatives (oximes, oxime ethers and a lactam) and one known compound were synthesized from 20-hydroxyecdysone 2,3;20,22-diacetonide and fully characterized by comprehensive NMR techniques revealing their complete 1 H and 13 C signal assignments. The compounds exerted moderate to strong in vitro antiproliferative activity on HeLa, SiHa, MCF-7 and MDA-MB-231 cell lines. Oxime and particularly oxime ether formation strongly increased their inhibitory activity on the efflux of rhodamine 123 by P-glycoprotein (P-gp), while the new ecdysteroid lactam did not interfere with the efflux function. All compounds exerted potent chemo-sensitizing activity towards doxorubicin on a mouse lymphoma cell line and on its MDR counterpart, and, on the latter, the lactam was found the most active. Because of its MDR-selective chemo-sensitizing activity with no functional effect on P-gp, this lactam is of high potential interest as a new lead for further antitumor studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

PubMed

Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima

2008-09-25

Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

76 FR 12563 - Oral Dosage Form New Animal Drugs; Spinosad and Milbemycin Oxime

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... spinosad and milbemycin oxime in dogs for the treatment and prevention of flea infestations and for the... and milbemycin oxime) Chewable Tablets in dogs for the treatment and prevention of flea infestations... chapter. (c) Conditions of use in dogs--(1) Amount. Administer once a month at a [[Page 12564

Spectroscopic and electrochemical characterization of some Schiff base metal complexes containing benzoin moiety.

PubMed

El-Shahawi, M S; Al-Jahdali, M S; Bashammakh, A S; Al-Sibaai, A A; Nassef, H M

2013-09-01

The ligation behavior of bis-benzoin ethylenediamine (B2ED) and benzoin thiosemicarbazone (BTS) Schiff bases towards Ru(3+), Rh(3+), Pd(2+), Ni(2+) and Cu(2+) were determined. The bond length of M-N and spectrochemical parameters (10Dq, β, B and LFSE) of the complexes were evaluated. The redox characteristics of selected complexes were explored by cyclic voltammetry (CV) at Pt working electrode in non aqueous solvents. Au mesh (100 w/in.) optically transparent thin layer electrode (OTTLE) was also used for recording thin layer CV for selected Ru complex. Oxidation of some complexes occurs in a consecutive chemical reaction of an EC type mechanism. The characteristics of electron transfer process of the couples M(2+)/M(3+) and M(3+)/M(4+) (M=Ru(3+), Rh(3+)) and the stability of the complexes towards oxidation and/or reduction were assigned. The nature of the electroactive species and reduction mechanism of selected electrode couples were assigned. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Water-soluble cationic derivatives of indirubin, the active anticancer component from Indigo naturalis.

PubMed

Ginzinger, Werner; Egger, Alexander; Mühlgassner, Gerhard; Arion, Vladimir B; Jakupec, Michael A; Galanski, Markus; Berger, Walter; Keppler, Bernhard K

2012-10-01

To overcome the problem of poor aqueous solubility and bioavailability of indirubin-3-oximes, the compounds were modified by attaching a quaternary ammonium group at the oxime moiety. Exploring the prodrug concept, an oxime ester with acetyl-l-carnitine was prepared, and the rate of its hydrolysis was investigated to assess its suitability for clinical administration. In addition, the cytotoxic potency of new stable oxime ethers with a choline moiety and their influence on the cell cycle were tested in human cancer cell lines. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

α-Diazo oxime ethers for N-heterocycle synthesis.

PubMed

Choi, Subin; Ha, Sujin; Park, Cheol-Min

2017-06-01

This Feature Article introduces the preparation and synthetic utility of α-diazo oxime ethers. α-Oximino carbenes are useful synthons for N-heterocycles, and can be easily prepared from α-diazo oxime ethers as precursors. We begin with the preparation of α-diazo oxime ethers and their application in [3+2] cycloaddition. It turns out that the nature of metals bound to carbenes plays a crucial role in modulating the reactivity of α-oximino carbenes, in which copper carbenes smoothly react with enamines, whereas the less reactive enol ethers and nitriles require gold carbenes. In Section 3.2, a discussion on N-O and C-H bond activation is presented. Carbenes derived from diazo oxime ethers show unique reactivity towards N-O and C-H bond activation, in which the proximity of the two functionalities, carbene and oxime ether, dictates the preferred reaction pathways toward pyridines, pyrroles, and 2H-azirines. In Section 3.3, the development of tandem reactions based on α-diazo oxime ethers is discussed. The nature of carbenes in which whether free carbenes or metal complexes are involved dissects the pathway and forms different types of 2H-azirines. The 2H-azirine formation turned out to be an excellent platform for the tandem synthesis of N-heterocycles including pyrroles and pyridines. In the last section, we describe the electrophilic activation of 2H-azirines with vinyl carbenes and oximino carbenes. The resulting azirinium species undergo rapid ring expansion rearrangements to form pyridines and pyrazines.

O-H bond dissociation enthalpies in oximes: order restored.

PubMed

Pratt, Derek A; Blake, Jessie A; Mulder, Peter; Walton, John C; Korth, Hans-Gert; Ingold, Keith U

2004-09-01

The O-H bond dissociation enthalpies (BDEs) of 13 oximes, RR'C=NOH, having R and/or R' = H, alkyl, and aryl are reported. Experimental anchor points used to validate the results of theoretical calculations include (1) the O-H BDEs of (t-Bu)2C=NOH, t-Bu(i-Pr)C=NOH, and t-Bu(1-Ad)C=NOH determined earlier from the heat released in the reaction of (t-Bu)2C=NO* with (PhNH)2 in benzene and EPR spectroscopy (Mahoney, L. R.; Mendenhall, G. D.; Ingold, K. U. J. Am. Chem. Soc. 1973, 95, 8610), all of which were decreased by 1.7 kcal/mol to reflect a revision to the heat of formation of (E)-azobenzene (which has significant ramifications for other BDEs) and to correct for the heat of hydrogen bonding of (t-Bu)2C=NOH (alphaH2 = 0.43 measured in this work) to benzene, and (2) the measured rates of thermal decomposition of six RR'C=NOCH2Ph at 423 or 443 K, which were used to derive O-H BDEs for the corresponding RR'C=NOH. Claims (Bordwell, F. G.; Ji, G. Z. J. Org. Chem. 1992, 57, 3019; Bordwell, F. G.; Zhang, S. J. Am. Chem. Soc. 1995, 117, 4858; and Bordwell, F. G.; Liu, W.-Z. J. Am. Chem. Soc. 1996, 118, 10819) that the O-H BDEs in mono- and diaryloximes are significantly lower than those for alkyloximes due to delocalization of the unpaired electron into the aromatic ring have always been inconsistent with the known structures of iminoxyl radicals as are the purported perpendicular structures, i.e., phi(Calpha-C=N-O*) = 90 degrees, for sterically hindered dialkyl iminoxyl radicals. The present results confirm the 1973 conclusion that simple steric effects, not electron delocalization or dramatic geometric changes, are responsible for the rather small differences in oxime O-H BDEs. Copyright 2004 American Chemical Society

Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists.

PubMed

Mohsen, Amal M Y; Mandour, Yasmine M; Sarukhanyan, Edita; Breitinger, Ulrike; Villmann, Carmen; Banoub, Maha M; Breitinger, Hans-Georg; Dandekar, Thomas; Holzgrabe, Ulrike; Sotriffer, Christoph; Jensen, Anders A; Zlotos, Darius P

2016-12-23

A series of (E)-11-isonitrosostrychnine oxime ethers, 2-aminostrychnine, (strychnine-2-yl)propionamide, 18-oxostrychnine, and N-propylstrychnine bromide were synthesized and evaluated pharmacologically at human α1 and α1β glycine receptors in a functional fluorescence-based and a whole-cell patch-clamp assay and in [ 3 H]strychnine binding studies. 2-Aminostrychnine and the methyl, allyl, and propargyl oxime ethers were the most potent α1 and α1β antagonists in the series, displaying IC 50 values similar to those of strychnine at the two receptors. Docking experiments to the strychnine binding site of the crystal structure of the α3 glycine receptor indicated the same orientation of the strychnine core for all analogues. For the most potent oxime ethers, the ether substituent was accommodated in a lipophilic receptor binding pocket. The findings identify the oxime hydroxy group as a suitable attachment point for linking two strychnine pharmacophores by a polymethylene spacer and are, therefore, important for the design of bivalent ligands targeting glycine receptors.

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

Borszeky, K.; Mallat, T.; Aeschiman, R.

The chemo- and enantioselective hydrogenation of pyruvic acid oxime have been studied on Pd/alumina, the latter in the presence of the 1,2-amino alcohol type alkaloids ephedrine, cinchonidine, and cinchonine. High yields of racemic alanine (90-98%) were obtained in the absence of alkaloids in polar solvents at 0-45{degrees}C and 10 bar. Enantioselection increased with higher temperature and alkalid: oxime molar ratio. A 1:1 ephedrine: oxime molar ratio afforded the best enantiomeric excess (26%). The presence of alkaloid resulted in a decrease of reaction rate by a factor of up to 140, compared to the racemic hydrogenation. Based on X-ray crystal structuremore » analysis of the alkaloid-pyruvic acid oxime adduct, a mechanism is proposed for the steric course of the reaction. Extended interactions by multiple H bonds between the adsorbed alkaloid-oxime salt units on the Pd surface is assumed to be at the origin of the moderate enantioselectivity and the very low enantioselective hydrogenation rate. 28 refs., 5 figs., 3 tabs.« less

Computational predictions of stereochemistry in asymmetric thiazolium- and triazolium-catalyzed benzoin condensations.

PubMed

Dudding, Travis; Houk, Kendall N

2004-04-20

The catalytic asymmetric thiazolium- and triazolium-catalyzed benzoin condensations of aldehydes and ketones were studied with computational methods. Transition-state geometries were optimized by using Morokuma's IMOMO [integrated MO (molecular orbital) + MO method] variation of ONIOM (n-layered integrated molecular orbital method) with a combination of B3LYP/6-31G(d) and AM1 levels of theory, and final transition-state energies were computed with single-point B3LYP/6-31G(d) calculations. Correlations between experiment and theory were found, and the origins of stereoselection were identified. Thiazolium catalysts were predicted to be less selective then triazolium catalysts, a trend also found experimentally.

Chiral magnetic microspheres purified by centrifugal field flow fractionation and microspheres magnetic chiral chromatography for benzoin racemate separation

PubMed Central

Tian, Ailin; Qi, Jing; Liu, Yating; Wang, Fengkang; Ito, Yoichiro; Wei, Yun

2013-01-01

Separation of enantiomers still remains a challenge due to their identical physical and chemical properties in a chiral environment, and the research on specific chiral selector along with separation techniques continues to be conducted to resolve individual enantiomers. In our laboratory the promising magnetic chiral microspheres Fe3O4@SiO2@cellulose-2, 3-bis (3, 5-dimethylphenylcarbamate) have been developed to facilitate the resolution using both its magnetic property and chiral recognition ability. In our present studies this magnetic chiral selector was first purified by centrifuge field flow fractionation, and then used to separate benzoin racemate by a chromatographic method. Uniform-sized and masking-impurity-removed magnetic chiral selector was first obtained by field flow fractionation with ethanol through a spiral column mounted on the type-J planetary centrifuge, and using the purified magnetic chiral selector, the final chromatographic separation of benzoin racemate was successfully performed by eluting with ethanol through a coiled tube (wound around the cylindrical magnet to retain the magnetic chiral selector as a stationary phase) submerged in dry ice. In addition, an external magnetic field facilitates the recycling of the magnetic chiral selector. PMID:23891368

NHC-catalysed benzoin condensation – is it all down to the Breslow intermediate?† †Electronic supplementary information (ESI) available: Characterisation data of products, substrates and catalysts, EPR and NMR spectra and progress curves as well as computational details are found. See DOI: 10.1039/c5sc02186c Click here for additional data file.

PubMed Central

Ruser, Stephanie-M.; Phan, Jenny

2015-01-01

The Breslow catalytic cycle describing the benzoin condensation promoted by N-heterocyclic carbenes (NHC) as proposed in the late 1950s has since then been tried by generations of physical organic chemists. Emphasis has been laid on proofing the existence of an enaminol like structure (Breslow intermediate) that explains the observed umpolung of an otherwise electrophilic aldehyde. The present study is not focusing on spectroscopic elucidation of a thiazolydene based Breslow intermediate but rather tries to clarify if this key-intermediate is indeed directly linked with the product side of the overall reaction. The here presented EPR-spectroscopic and computational data provide a fundamentally different view on how the benzoin condensation may proceed: a radical pair could be identified as a second key-intermediate that is derived from the Breslow-intermediate via an SET process. These results highlight the close relationship to the Cannizarro reaction and oxidative transformations of aldehydes under NHC catalysis. PMID:29449915

Pharmacokinetics and Pharmacodynamics of Oximes in Unanesthetized Pigs

DTIC Science & Technology

1991-04-01

D-A234 036 U.S. ARMY MEDICAL RESEARCH p INSTITUTE OF CHEMICAL DEFENSE USAMRICD-TR-91-07 PHARMACOKINETICS AND PHARMACODYNAMICS OF OXIMES IN...SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP 2-PAM Cl, ICD 467, MMB-4, Pharmacokinetics ...Cardiovascular 06 15 Pharmacodynamics, Oximes06 15 19. ABSTRACT (Continue on reverse if necessary and identify by block number) The pharmacokinetics and

Potent 3-Hydroxy-2-Pyridine Aldoxime Reactivators of Organophosphate-Inhibited Cholinesterases with Predicted Blood-Brain Barrier Penetration.

PubMed

Zorbaz, Tamara; Braïki, Anissa; Maraković, Nikola; Renou, Julien; de la Mora, Eugenio; Maček Hrvat, Nikolina; Katalinić, Maja; Silman, Israel; Sussman, Joel L; Mercey, Guillaume; Gomez, Catherine; Mougeot, Romain; Pérez, Belén; Baati, Rachid; Nachon, Florian; Weik, Martin; Jean, Ludovic; Kovarik, Zrinka; Renard, Pierre-Yves

2018-04-19

A new series of 3-hydroxy-2-pyridine aldoxime compounds have been designed, synthesised and tested in vitro, in silico, and ex vivo as reactivators of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) inhibited by organophosphates (OPs), for example, VX, sarin, cyclosarin, tabun, and paraoxon. The reactivation rates of three oximes (16-18) were determined to be greater than that of 2-PAM and comparable to that of HI-6, two pyridinium aldoximes currently used by the armies of several countries. The interactions important for a productive orientation of the oxime group within the OP-inhibited enzyme have been clarified by molecular-modelling studies, and by the resolution of the crystal structure of the complex of oxime 17 with Torpedo californica AChE. Blood-brain barrier penetration was predicted for oximes 15-18 based on their physicochemical properties and an in vitro brain membrane permeation assay. Among the evaluated compounds, two morpholine-3-hydroxypyridine aldoxime conjugates proved to be promising reactivators of OP-inhibited cholinesterases. Moreover, efficient ex vivo reactivation of phosphylated native cholinesterases by selected oximes enabled significant hydrolysis of VX, sarin, paraoxon, and cyclosarin in whole human blood, which indicates that the oximes have scavenging potential. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oximes in Acute Organophosphate Pesticide Poisoning: a Systematic Review of Clinical Trials

PubMed Central

Eddleston, Michael; Szinicz, Ladislaus; Eyer, Peter; Buckley, Nick

2006-01-01

Acute organophosphate (OP) pesticide poisoning causes tens of thousands of deaths each year across the developing world. Standard treatment involves the administration of intravenous atropine and oxime to counter acetylcholinesterase inhibition at the synapse. The usefulness of oximes, such as pralidoxime and obidoxime, has however been challenged over the past 20 years by physicians in many parts of the world who have failed to see benefit in their clinical practice. We have carried out a systematic review to find randomised controlled trials (RCTs) of oximes in OP poisoning. Two RCTs have been published involving 182 patients treated with pralidoxime. The RCTs did not find benefit with pralidoxime and have been used to argue that pralidoxime should not be used in OP poisoning. These physicians must be congratulated for attempting important studies in a difficult environment. However, the studies did not take into account recently clarified issues important for outcome and the published methodology is unclear, therefore such a generalised statement cannot be supported by the published results. There are many reasons why oximes may not be relevant in the overwhelming self-poisoning typical of the tropics. However, we believe that a large RCT is required to compare the current WHO-recommended pralidoxime regimen (>30mg/kg bolus followed by >8mg/kg/hr infusion) with placebo to determine definitively the role of oxime therapy in OP self-poisoning. Such a study will need to be designed with pre-defined subgroup analysis to allow the identification of patient subgroups that may benefit from oximes. PMID:11978898

Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

PubMed Central

Antonijevic, Biljana; Stojiljkovic, Milos P.

2007-01-01

The use of organophosphorus pesticides results in toxicity risk to non-target organisms. Organophosphorus compounds share a common mode of action, exerting their toxic effects primarily via acetylcholinesterase (AChE) inhibition. Consequently, acetylcholine accumulates in the synaptic clefts of muscles and nerves, leading to overstimulation of cholinergic receptors. Acute cholinergic crisis immediately follows exposure to organophosphate and includes signs and symptoms resulting from hyperstimulation of central and peripheral muscarinic and nicotinic receptors. The current view of the treatment of organophosphate poisoning includes three strategies, i.e. the use of an anticholinergic drug (e.g., atropine), cholinesterase-reactivating agents (e.g., oximes) and anticonvulsant drugs (e.g., benzodiazepines). Oximes, as a part of antidotal therapy, ensure the recovery of phosphylated enzymes via a process denoted as reactivation of inhibited AChE. However, both experimental results and clinical findings have demonstrated that different oximes are not equally effective against poisonings caused by structurally different organophosphorus compounds. Therefore, antidotal characteristics of conventionally used oximes can be evaluated regarding how close the certain substance is to the theoretical concept of the universal oxime. Pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LüH-6), HI-6 and HLö-7 have all been demonstrated to be very effective in experimental poisonings with sarin and VX. TMB-4 and LüH-6 may reactivate tabun-inhibited AChE, whereas HI-6 possesses the ability to reactivate the soman-inhibited enzyme. An oxime HLö-7 seems to be an efficient reactivator of AChE inhibited by any of the four organophosphorus warfare agents. According to the available literature, the oximes LüH-6 and TMB-4, although relatively toxic, are the most potent to induce reactivation of AChE inhibited by the majority of organophosphorus pesticides. Since there are no reports of controlled clinical trials on the use of TMB-4 in human organophosphate pesticide poisoning, LüH-6 may be a better option. PMID:17456837

A Structure-Activity Analysis of the Variation in Oxime Efficacy Against Nerve Agents

DTIC Science & Technology

2008-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A structure- activity analysis of the variation in oxime...structure– activity analysis of the variation in oxime efficacy against nerve agents☆ Donald M. Maxwell a,⁎, Irwin Koplovitz a, Franz Worek b, Richard E...structure– activity analysi Received 22 February 2008 Revised 8 April 2008 Accepted 13 April 2008 Available online 22 April 2008 Keywords: Organophosphorus

A Comprehensive Evaluation of the Efficacy of Leading Oxime Therapies in Guinea Pigs Exposed to Organophosphorus Chemical Warfare Agents or Pesticides

PubMed Central

Wilhelm, Christina M.; Snider, Thomas H.; Babin, Michael C.; Jett, David A.; Platoff, Gennady E.; Yeung, David T.

2014-01-01

The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl2, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 hours post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman’s method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. PMID:25448441

In vitro effects of acetylcholinesterase reactivators on monoamine oxidase activity.

PubMed

Fišar, Zdeněk; Hroudová, Jana; Korábečný, Jan; Musílek, Kamil; Kuča, Kamil

2011-03-05

Administration of acetylcholinesterase (AChE) reactivators (oximes) is usually used in order to counteract the poisoning effects of nerve agents. The possibility was suggested that oximes may show some therapeutic and/or adverse effects through their action in central nervous system. There are no sufficient data about interaction of oximes with monoaminergic neurotransmitter's systems in the brain. Oxime-type AChE reactivators pralidoxime, obidoxime, trimedoxime, methoxime and HI-6 were tested for their potential to affect the activity of monoamine oxidase of type A (MAO-A) and type B (MAO-B) in crude mitochondrial fraction of pig brains. The compounds were found to inhibit fully MAO-A with half maximal inhibitory concentration (IC(50)) of 0.375 mmol/l (pralidoxime), 1.53 mmol/l (HI-6), 2.31 mmol/l (methoxime), 2.42 mmol/l (obidoxime) and 4.98 mmol/l (trimedoxime). Activity of MAO-B was fully inhibited by HI-6 and pralidoxime only with IC(50) 4.81 mmol/l and 11.01 mmol/l, respectively. Methoxime, obidoxime and trimedoxime displayed non-monotonic concentration dependent effect on MAO-B activity. Because oximes concentrations effective for MAO inhibition could not be achieved in vivo at the cerebral level, we suppose that oximes investigated do not interfere with brain MAO at therapeutically relevant concentrations. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Efficacy of afoxolaner plus milbemycin oxime chewable tablets (NexGard Spectra®, Merial) against adult Ancylostoma ceylanicum hookworm, in dogs.

PubMed

Tielemans, E; Lebon, W; Dumont, P; Taweethavonsawat, P; Larsen, D; Rehbein, S

2017-04-30

A fixed-combination chewable tablet incorporating afoxolaner plus milbemycin oxime (NexGard Spectra ® , Merial) was tested in purpose-bred Beagle dogs for efficacy against adult Ancylostoma ceylanicum hookworms. Sixteen dogs were inoculated each by oral administration of approximately 500 infective larvae of A. ceylanicum. Seventeen days after inoculation, the dogs were weighed and allocated randomly to be treated with afoxolaner plus milbemycin oxime chewable tablets or to remain untreated. Commercial chewable tablets of different strength were combined to deliver doses as close as possible to the minimum effective dose of 2.5mg afoxolaner plus 0.5mg milbemycin oxime per kg body weight. Parasites were recovered and counted for determination of efficacy seven days after treatment. All eight dogs that had been left untreated were harboring adult A. ceylanicum (geometric mean, 317.8; range, 210-428) while only one and nine A. ceylanicum were recovered from two of the eight dogs treated with afoxolaner plus milbemycin oxime chewable tablets (geometric mean, 0.5; p<0.0001). Thus, 99.9% efficacy against induced infection of A. ceylanicum was obtained by the use of oral NexGard Spectra ® at the minimum effective dose. Treatment with afoxolaner plus milbemycin oxime chewable tablets was well accepted and safe. Copyright © 2017 Elsevier B.V. All rights reserved.

Computational predictions of stereochemistry in asymmetric thiazolium- and triazolium-catalyzed benzoin condensations

PubMed Central

Dudding, Travis; Houk, Kendall N.

2004-01-01

The catalytic asymmetric thiazolium- and triazolium-catalyzed benzoin condensations of aldehydes and ketones were studied with computational methods. Transition-state geometries were optimized by using Morokuma's IMOMO [integrated MO (molecular orbital) + MO method] variation of ONIOM (n-layered integrated molecular orbital method) with a combination of B3LYP/6–31G(d) and AM1 levels of theory, and final transition-state energies were computed with single-point B3LYP/6–31G(d) calculations. Correlations between experiment and theory were found, and the origins of stereoselection were identified. Thiazolium catalysts were predicted to be less selective then triazolium catalysts, a trend also found experimentally. PMID:15079058

Synthesis and spectral studies of platinum metal complexes of benzoin thiosemicarbazone

NASA Astrophysics Data System (ADS)

Offiong, Offiong E.

1994-11-01

The platinum metal chelates of benzoin thiosemicarbazone obtained with Ru(III), Rh(III), Ir(III), Pd(II) and Pt(II) were prepared from their corresponding halide salts. The complexes were characterized by elemental analysis, conductance measurement, IR, Raman, 1H-NMR, 13C-NMR and UV-visible spectra studies. Various ligand field parameters and nephelauxetic parameters were also calculated. The mode of bonding and the geometry of the ligand environment around the metal ion have been discussed in the light of the available data obtained. Complexes of Ru(III), Rh(III) and Ir(III) are six-coordinate octahedral, while Pd(II) and Pt(II) halide complexes are four-coordinated with halides bridging.

Reactivation of model cholinesterases by oximes and intermediate phosphyloximes: A computational study

PubMed Central

Vyas, Shubham; Hadad, Christopher M.

2008-01-01

Phosphyloximes (POX) are generated upon the reactivation of organophosphorus (OP) inhibited cholinesterases (ChEs) by pyridinium oximes. These POXs are known to be potent inhibitors of the ChEs following reactivation. However, they can also decompose to give an OP derivative and a cyano derivative of the oxime when a base abstracts the benzylic proton. Using density functional theory, thermodynamic properties were calculated for the reactivation and decomposition pathways of three different oximes (2-PAM, 3-PAM and 4-PAM) with six different OPs (cyclosarin, paraoxon, sarin, tabun, VR and VX). For reactivation purposes, 2-PAM is predicted to be more efficient than 3- and 4-PAM. Based on atomic charges and relative energies, 2-POXs were found to be more inclined towards the decomposition process. PMID:18582852

Kinetic Resolution of α-Hydroxy-Substituted Oxime Ethers by Enantioselective Cu-H-Catalyzed Si-O Coupling.

PubMed

Dong, Xichang; Kita, Yuji; Oestreich, Martin

2018-04-12

A catalyst-controlled enantioselective alcohol silylation by Cu-H-catalyzed dehydrogenative Si-O coupling of hydroxy groups α to an oxime ether and simple hydrosilanes is reported. The selectivity factors reached in this kinetic resolution are generally high (s≈50), and these reactions thereby provide reliable access to highly enantioenriched α-hydroxy-substituted oxime ethers. The synthetic usefulness of these compounds is also demonstrated. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of Imidazopyridines via Copper-Catalyzed, Formal Aza-[3 + 2] Cycloaddition Reaction of Pyridine Derivatives with α-Diazo Oxime Ethers.

PubMed

Park, Sangjune; Kim, Hyunseok; Son, Jeong-Yu; Um, Kyusik; Lee, Sooho; Baek, Yonghyeon; Seo, Boram; Lee, Phil Ho

2017-10-06

The Cu-catalyzed, formal aza-[3 + 2] cycloaddition reaction of pyridine derivatives with α-diazo oxime ethers in trifluoroethanol was used to synthesize imidazopyridines via the release of molecular nitrogen and elimination of alcohol. These methods enabled modular synthesis of a wide range of N-heterobicyclic compounds such as imidazopyridazines, imidazopyrimidines, and imidazopyrazines with an α-imino Cu-carbenoid generated from the α-diazo oxime ethers and copper.

Quantum Chemical and Physicochemical Studies of Oximes (Prophylactics against and Reactivators of Phosphorylated AChE).

DTIC Science & Technology

1984-10-25

crystal structure of nicotinic acid ,. and we used the ether bridge from the crystal structure of dimethyl ether. We are investigating various rotamers...observations were made: - The titration curve (after the subtraction of the blank curve) shows only one titrable group, i.e. the oxime moiety. - The...subtraction of the blank curve, shows two titrable groups, i.e. the two oxime moieties. The results are as follows: Temperature Conditions PKa pK2

Efficacy of the Tertiary Oxime Monoisonitrosoacetone (MINA) Against Lethal Sarin Intoxication in the Guinea Pig

DTIC Science & Technology

2007-10-01

Sarin 5a. CONTRACT NUMBER Intoxication in the Guinea Pig 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Koplovitz, I and...efficacy of MINA as a treatment for lethal sarin (GB) intoxication in guinea pigs . Male animals were challenged subcutaneously (s.c.) with 2 LD50s...oximes that are readily able to enter the brain. 15. SUBJECT TERMS oximes, brain, sarin, reactivation, nerve agents, guinea pigs 16. SECURITY

Chiral magnetic microspheres purified by centrifugal field flow fractionation and microspheres magnetic chiral chromatography for benzoin racemate separation.

PubMed

Tian, Ailin; Qi, Jing; Liu, Yating; Wang, Fengkang; Ito, Yoichiro; Wei, Yun

2013-08-30

Separation of enantiomers still remains a challenge due to their identical physical and chemical properties in a chiral environment, and the research on specific chiral selector along with separation techniques continues to be conducted to resolve individual enantiomers. In our laboratory the promising magnetic chiral microspheres Fe3O4@SiO2@cellulose-2, 3-bis (3,5-dimethylphenylcarbamate) have been developed to facilitate the resolution using both its magnetic property and chiral recognition ability. In our present studies this magnetic chiral selector was first purified by centrifuge field flow fractionation, and then used to separate benzoin racemate by a chromatographic method. Uniform-sized and masking-impurity-removed magnetic chiral selector was first obtained by field flow fractionation with ethanol through a spiral column mounted on the type-J planetary centrifuge, and using the purified magnetic chiral selector, the final chromatographic separation of benzoin racemate was successfully performed by eluting with ethanol through a coiled tube (wound around the cylindrical magnet to retain the magnetic chiral selector as a stationary phase) submerged in dry ice. In addition, an external magnetic field facilitates the recycling of the magnetic chiral selector. Copyright © 2013 Elsevier B.V. All rights reserved.

Population-specific responses to light influence herbivory in the understory shrub Lindera benzoin.

PubMed

Mooney, E H; Niesenbaum, R A

2012-12-01

Plants display photosynthetic plasticity in response to variation in light environment, and the extent of this plasticity often varies with genotype, i.e., genotype x environment interaction. Herbivory may also covary with light environment as a result of light-induced changes in photosynthetic traits. For example, greater levels of photoprotective phenolic compounds in high-light environments may reduce host quality to herbivores. We investigated intraspecific variation in photosynthetic responses to light and its consequences for herbivory in the understory shrub, Lindera benzoin (Lauraceae). We transplanted five plants from eight populations (N = 240) into three replicate sun and shade common gardens. Two years after transplantation, we tested for population x light environment interactions in six photosynthesis-related responses: specific leaf area, water content, chlorophyll content, chlorophyll fluorescence (F(0)), maximum quantum yield (F(v)/F(m)), and total phenolics. We assessed seasonal herbivory and consumption by a specialist lepidopteran herbivore (Epimecis hortaria). This allowed us to test for (1) population-specific patterns of photosynthetic acclimation and photoinhibition, (2) population-specific production of phenolics in response to photoinhibition, and (3) population-specific photosynthetic responses that contribute to population x light environment interactions in herbivory. Population X light environment interactions were insignificant in leaf variables but statistically significant for herbivory measured as consumption by E. hortaria. We found similar trends for population x light environment interactions in seasonal herbivory. Total phenolics and minimum chlorophyll fluorescence (F(0)) were significant covariates with herbivory, but their effects depended on light environment and population of origin. High-light environments eliminated differences among populations in how these leaf variables affected herbivory, while population-specific relationships were apparent in the shade. Analysis of total phenolics revealed that they were likely induced by photoinhibition, but that this response varied among the populations we assessed. However, phenolics increased herbivory in L. benzoin, which would limit the fitness value of this protective response to light-induced photoinhibition. Our results suggest that herbivores could affect evolution of photosynthetic plasticity in L. benzoin.

Phenoseasonal subcanopy light dynamics and the effects of light on the physiological ecology of a common understory shrub, Lindera benzoin.

PubMed

Hudson, Janice E; Levia, Delphis F; Hudson, Sean A; Bais, Harsh P; Legates, David R

2017-01-01

The purpose of this work was to quantify the variation of subcanopy spatiotemporal light dynamics over the course of a year and to link it to the physiological ecology of the understory shrub, Lindera benzoin L. Blume (northern spicebush). Covering all seven phenoseasons of a deciduous forest, this work utilized a line quantum sensor to measure the variation in subcanopy light levels under all sky conditions at different times of the day. A total of 4,592 individual subcanopy measurements of photosynthetic photon flux density (PPFD, μmol m-2 s-1) were taken as 15-second spatially-integrated one-meter linear averages to better understand the dynamism of light exposure to L. benzoin. Both open (n = 2, one continuous and one instantaneous) and subcanopy location (n = 25) measurements of PPFD were taken on each sampling date in and near the forested plot (Maryland, USA). In addition, we explored the effect of four photointensity-photoperiod combinations on the growth of L. benzoin under controlled conditions to compare to field conditions. On average, understory PPFD was less than 2% of open PPFD during the leafed months and an average of 38.8% of open PPFD during leafless winter months, indicating that: (1) often overlooked woody surfaces intercept large amounts of light; and (2) spicebush within the plot receive limited light even in early spring before canopy leaf-out. Statistical results suggested phenoseason accounted for nearly three-quarters of the variation in incident radiation between the three plant canopy heights. Spicebush under controlled conditions exhibited the highest fitness levels at an intensity of 164.5 μmol m-2 s-1 for 12-hour duration. Similarly, spicebush growth in the field occurred at subcanopy locations receiving higher incidence of PPFD (i.e., >128 μmol m-2 s-1). Results suggest that the ecological niche for these plants is very specific in terms of light intensity.

Phenoseasonal subcanopy light dynamics and the effects of light on the physiological ecology of a common understory shrub, Lindera benzoin

PubMed Central

Levia, Delphis F.; Hudson, Sean A.; Bais, Harsh P.; Legates, David R.

2017-01-01

The purpose of this work was to quantify the variation of subcanopy spatiotemporal light dynamics over the course of a year and to link it to the physiological ecology of the understory shrub, Lindera benzoin L. Blume (northern spicebush). Covering all seven phenoseasons of a deciduous forest, this work utilized a line quantum sensor to measure the variation in subcanopy light levels under all sky conditions at different times of the day. A total of 4,592 individual subcanopy measurements of photosynthetic photon flux density (PPFD, μmol m-2 s-1) were taken as 15-second spatially-integrated one-meter linear averages to better understand the dynamism of light exposure to L. benzoin. Both open (n = 2, one continuous and one instantaneous) and subcanopy location (n = 25) measurements of PPFD were taken on each sampling date in and near the forested plot (Maryland, USA). In addition, we explored the effect of four photointensity-photoperiod combinations on the growth of L. benzoin under controlled conditions to compare to field conditions. On average, understory PPFD was less than 2% of open PPFD during the leafed months and an average of 38.8% of open PPFD during leafless winter months, indicating that: (1) often overlooked woody surfaces intercept large amounts of light; and (2) spicebush within the plot receive limited light even in early spring before canopy leaf-out. Statistical results suggested phenoseason accounted for nearly three-quarters of the variation in incident radiation between the three plant canopy heights. Spicebush under controlled conditions exhibited the highest fitness levels at an intensity of 164.5 μmol m-2 s-1 for 12-hour duration. Similarly, spicebush growth in the field occurred at subcanopy locations receiving higher incidence of PPFD (i.e., >128 μmol m-2 s-1). Results suggest that the ecological niche for these plants is very specific in terms of light intensity. PMID:29023480

Effect of Several New and Currently Available Oxime Cholinesterase Reactivators on Tabun-intoxicated Rats

PubMed Central

Karasova, Jana Zdarova; Kassa, Jiri; Jung, Young-Sik; Musilek, Kamil; Pohanka, Miroslav; Kuca, Kamil

2008-01-01

The therapeutical efficacies of eleven oxime-based acetylcholinesterase reactivators were compared in an in vivo (rat model) study of treatment of intoxication caused by tabun. In this group there were some currently available oximes (obidoxime, trimedoxime and HI-6) and the rest were newly synthesized compounds. The best reactivation efficacy for acetylcholinesterase in blood (expressed as percent of reactivation) among the currently available oximes was observed after administration of trimedoxime (16%) and of the newly synthesized K127 (22432) (25%). The reactivation of butyrylcholinesterase in plasma was also studied; the best reactivators were trimedoxime, K117 (22435), and K127 (22432), with overall reactivation efficacies of approximately 30%. Partial protection of brain ChE against tabun inhibition was observed after administration of trimedoxime (acetylcholinesterase 20%; butyrylcholinesterase 30%) and obidoxime (acetylcholinesterase 12%; butyrylcholinesterase 16%). PMID:19330072

Oximes of αω-diquaternary alkane salts as antidotes to organophosphate anticholinesterases

PubMed Central

Berry, W. K.; Davies, D. R.; Green, A. L.

1959-01-01

Sixteen compounds of the general structure {HON: CH.C5H4N+.[CH2]n.R+}2Br- have been synthesized in which the position of the oxime group in the pyridine ring, the second charged group R+ and the number of methylene groups between the charged atoms have been varied. The rate at which these compounds reactivate cholinesterase inhibited by ethyl pyrophosphate has been studied and a number have been found which are more active than 2-hydroxyiminomethyl-N-methylpyridinium methanesulphonate. Since considerable variation in structure was found among those compounds which are better reactivators than the latter, the concept that 2-hydroxyiminomethyl-N-methylpyridinium salts are unique in their ability to fit the surface of the inhibited enzyme is no longer tenable. The reactivating power of these oximes correlated well with their ability, when given in conjunction with atropine, to save the lives of mice poisoned by ethyl pyrophosphate. The most effective compounds, NN'-trimethylenebis-(4-hydroxyiminomethylpyridinium bromide) and NN'-hexamethylenebis(2-hydroxyiminomethylpyridinium bromide), contained a further oxime group in R+, but the second oxime group was not essential for high activity. These new oximes were also superior in saving the lives of mice poisoned with sarin (isopropyl methylphosphonofluoridate), but the improvement was not as dramatic as when the mice were poisoned with ethyl pyrophosphate. The toxicity of the compounds varied with both n and R+ and was unrelated to the therapeutic potency. PMID:13662572

Construction of New Potential Reactivators of Phosphonylated Acetylcholinesterase. Substitution of F for H in the Nucleus of Pyridinecarboxaldehyde Oximes.

DTIC Science & Technology

1982-11-01

interpretation in this report have been entered in typography to insure legibility. 4 u 4A V * i List of Figures Page Fig. la HPLC chromatogram of...crude oximation reaction mixture (4 nMoles) 14 Fig. lb HPLC chromatogram of crude oximation reaction mixture (20 nMoles) 15 Fig. 2a HPLC chromatogram of...of classical organic reactions starting with commercial 2-Amino-4-picoline and progressing to 3-Fluoro-4-picoline. The latter compound was then

Isolation and expression of a Bacillus cereus gene encoding benzil reductase.

PubMed

Maruyama, R; Nishizawa, M; Itoi, Y; Ito, S; Inoue, M

2001-12-20

Benzil was reduced stereospecifically to (S)-benzoin by Bacillus cereus strain Tim-r01. To isolate the gene responsible for asymmetric reduction, we constructed a library consisting of Escherichia coli clones that harbored plasmids expressing Bacillus cereus genes. The library was screened using the halo formation assay, and one clone showed benzil reduction to (S)-benzoin. Thus, this clone seemed to carry a plasmid encoding a Bacillus cereus benzil reductase. The deduced amino acid sequence had marked homologies to the Bacillus subtilis yueD protein (41% identity), the yeast open reading frame YIR036C protein (31%), and the mammalian sepiapterin reductases (28% to 30%), suggesting that benzil reductase is a novel short-chain de-hydrogenases/ reductase. Copyright 2001 John Wiley & Sons, Inc.

Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3Kα).

PubMed

Sabbah, Dima A; Saada, Musaab; Khalaf, Reema Abu; Bardaweel, Sanaa; Sweidan, Kamal; Al-Qirim, Tariq; Al-Zughier, Amani; Halim, Heba Abdel; Sheikha, Ghassan Abu

2015-08-15

The oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has made it an attractive target for anticancer drug design. In this work, we describe our efforts to optimize the lead PI3Kα inhibitor 2-hydroxy-1,2-diphenylethanone (benzoin). A series of 2-oxo-1,2-diphenylethyl benzoate analogs were identified as potential PI3Kα inhibitors. Docking studies confirmed that the aromatic interaction is mediating ligand/protein complex formation and identified Lys802 and Val851 as H-bonding key residues. Our biological data in human colon carcinoma HCT116 showed that the structure analogs inhibited cell proliferation and induced apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Computational study of the synthesis of benzoin derivatives from benzil

NASA Astrophysics Data System (ADS)

Topal, Kevser Göçmen; Unaleroglu, Canan; Aviyente, Viktorya

Benzil (1,2-diphenylethane-1,2-dione) undergoes cyanide catalyzed condensation with benzaldehyde to yield O-benzoylated benzoin (2-benzoyl-1,2-diphenylethanone). In this study, the experimentally suggested mechanism has been modeled with PM3 and verified with B3LYP. The effect of the substituent on the reaction yield has been rationalized by considering two benzil derivatives; 1,2-bis(2-chlorophenyl)ethane-1,2-dione and 1,2-bis(2-fluorophenyl)ethane-1,2-dione and three benzaldehyde derivatives; o-fluorobenzaldehyde, o-methylbenzaldehyde and 2-pyridinecarboxaldehyde. The effect of the solvent has been modeled by using the isodensity-surface polarizable continuum (IPCM) model. Reactivity descriptors have been used to justify the reactivity differences of the various substituents.

Lewis Acid-Assisted Photoinduced Intermolecular Coupling between Acylsilanes and Aldehydes: A Formal Cross Benzoin-Type Condensation.

PubMed

Ishida, Kento; Tobita, Fumiya; Kusama, Hiroyuki

2018-01-12

Intermolecular carbon-carbon bond-forming reaction between readily available acylsilanes and aldehydes was achieved under photoirradiation conditions with assistance of a catalytic amount of Lewis acid. Nucleophilic addition of photochemically generated siloxycarbenes to aldehydes followed by 1,4-silyl migration afforded synthetically useful α-siloxyketones. Electrophilic activation of aldehydes by Lewis acid is highly important to realize this reaction efficiently, otherwise the yield of the desired coupling products were significantly decreased. Noteworthy is that a formal cross benzoin-type reaction using acylsilanes was achieved under Lewis acidic conditions. This is the first example of Lewis acid-catalyzed reaction of photochemically generated siloxycarbenes with electrophiles. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric reduction of benzil to (S)-benzoin with whole cells of Bacillus cereus.

PubMed

Saito, Tomoya; Maruyama, Reiji; Ono, Shin; Yasukawa, Nobuo; Kodaira, Ken-ichi; Nishizawa, Mikio; Ito, Seiji; Inoue, Masami

2003-12-01

Benzil (1) was selectively reduced to (S)-benzoin (2) in the presence of a wild-type Bacillus cereus Tim-r01. A 92% yield of 2 with 94% enantiomeric excess ratio was attained in phosphate-buffered saline (PBS) (pH 7.5) by using glucose as a nutrient at 37 degrees C for 12 h. Compound 2 was not reduced further to hydrobenzoin (3) at all. The reduction activity differed greatly depending on the strain of B. cereus. Under these conditions the B. cereus strains IFO3001, IFO15305, IAM1110, IAM1229, IAM1656, and IAM1729 gave 2 in yields ranging from 23 to 46% and the configuration of 2 was (S)-form (7 to 86% ee).

Impact of ultrasound on hydrophobic interactions in solutions: ultrasonic retardation of benzoin condensation.

PubMed

Hagu, Hannes; Salmar, Siim; Tuulmets, Ants

2007-04-01

Kinetics of the benzoin condensation of benzaldehyde in presence of KCN as the catalyst in water and in ethanol-water binary solutions were investigated without sonication and under ultrasound at 22 kHz. A statistically significant 20% decrease of the rate was observed in water. The retardation effect of ultrasound gradually decreases up to 45 wt% ethanol content. We report an evidence of ultrasonic retardation of reactions and thereby a direct evidence for sonochemical processes in the bulk solution. Ultrasound can disturb solvation of the species in the solution. If breaking down the stabilization of the encounter complexes between the reagents, sonication hinders the reaction while perturbation of the solvent-stabilization of the reagents accelerates the reaction.

Plant species evaluated for new crop potential

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

Carr, M.E.

1985-01-01

Ninety-two plant species from various regions of the USA were screened for their energy-producing potential. Samples were analysed for oil, polyphenol, hydrocarbon and protein. Oil fractions of some species were analysed for classes of lipid constituents and yields of unsaponifiable matter and fatty acids were determined. Hydrocarbon fractions of some species were analysed for rubber, gutta and waxes. Average MW and MW distribution of rubber and gutta were determined. Complete analytical data for 16 species is presented. Large quantities of oil were obtained from Philadelphus coronarius, Cacalia muhlenbergii, Lindera benzoin and Koelreuteria paniculata. High yields of polyphenols came from Acermore » ginnala, Cornus obliqua and Salix caprea and maximum yields of hydrocarbon and protein were from Elymus virginicus and Lindera benzoin, respectively.« less

Cutaneous exposure to vesicant phosgene oxime: Acute effects on the skin and systemic toxicity

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

Tewari-Singh, Neera, E-mail: Neera.tewari-singh@uc

Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model. Results from our study show that topical cutaneous exposure to CX vapor causes blanchingmore » of exposed skin with an erythematous ring, necrosis, edema, mild urticaria and erythema within minutes after exposure out to 8 h post-exposure. These clinical skin manifestations were accompanied with increases in skin thickness, apoptotic cell death, mast cell degranulation, myeloperoxidase activity indicating neutrophil infiltration, p53 phosphorylation and accumulation, and an increase in COX-2 and TNFα levels. Topical CX-exposure also resulted in the dilatation of the peripheral vessels with a robust increase in RBCs in vessels of the liver, spleen, kidney, lungs and heart tissues. These events could cause a drop in blood pressure leading to shock, hypoxia and death. Together, this is the first report on effects of CX cutaneous exposure, which could help design further comprehensive studies evaluating the acute and chronic skin injuries from CX topical exposure and elucidate the related mechanism of action to aid in the identification of therapeutic targets and mitigation of injury. - Highlights: • Phosgene oxime cutaneous exposure causes skin blanching, edema and urticaria. • Penetration of phosgene oxime causes dilation of vasculature in internal organs. • Mast cells could play an important role in phosgene oxime-induced skin injury. • Phosgene oxime could induce low blood pressure and hypoxia leading to mortality. • Data is significant for developing a phosgene oxime-induced skin injury model.« less

Three oxime ether derivatives: Synthesis, crystallographic study, electronic structure and molecular electrostatic potential calculation

NASA Astrophysics Data System (ADS)

Dey, Tanusri; Praveena, Koduru Sri Shanthi; Pal, Sarbani; Mukherjee, Alok Kumar

2017-06-01

Three oxime ether derivatives, (E)-3-methoxy-4-(prop-2-ynyloxy)-benzaldehyde-O-prop-2-ynyl-oxime (C14H13NO3) (2), benzophenone-O-prop-2-ynyl-oxime (C16H13NO) (3) and (E)-2-chloro-6-methylquinoline-3-carbaldehyde-O-prop-2-ynyl-oxime (C14H11ClN2O) (4), have been synthesized and their crystal structures have been determined. The DFT optimized molecular geometries in 2-4 agree closely with those obtained from the crystallographic study. An interplay of intermolecular Csbnd H⋯O, Csbnd H⋯N, Csbnd H⋯Cl and Csbnd H···π(arene) hydrogen bonds and π···π interactions assembles molecules into a 2D columnar architecture in 2, a 1D molecular ribbon in 3 and a 3D framework in 4. Hirshfeld surface analysis showed that the structures of 2 and 3 are mainly characterized by H⋯H, H⋯C and H⋯O contacts but some contribution of H⋯N and H⋯Cl contacts is also observed in 4. Hydrogen-bond based interactions in 2-4 have been complemented by calculating molecular electrostatic potential (MEP) surfaces. The electronic structures of molecules reveal that the estimated band gap in 3, in which both aldehyde hydrogen atoms of formaldehyde-O-prop-2-ynyl-oxime (1) have been substituted by two benzene rings, is higher than that of 2 and 4 with only one aldehyde hydrogen atom replaced.

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

Parker, B. F.; Hohloch, S.; Pankhurst, J. R.

Vanadium is the main competitor for uranium extraction from seawater, and V( iv ) comprises a minor but important portion of this. V( iv ) undergoes redox reactions with oximes and amidoxime ligands under seawater-relevant conditions, leading to V( v ) complexes and loss of oxime functional groups.

Free-radical mediated synthesis of enantiomerically pure, highly functionalized inositols from carbohydrates.

PubMed

Marco-Contelles, J; Pozuelo, C; de Opazo, E

2001-06-15

We report the synthesis, free-radical cyclization of precursors 1,2,7-trideoxy-7-iodo-3,4:5,6-di-O-isopropylidene-D-gluco-hept-1-enitol (1), methyl 7-O-acetyl-6-O-benzyl-8-bromo-2,3,8-trideoxy-4,5-O-isopropylidene-D-gluco-oct-2-enonate (2) and 5-O-acetyl-4-O-benzyl-6-bromo-6-deoxy-2,3-O-isopropylidene-D-glucose-O-benzyloxime (3), readily prepared from D-glucose, and some selected transformations of the carbocycles obtained from these intermediates. In compound 1 we have installed a terminal double bond and an iodide as radical acceptor and leaving group, respectively. Compounds 2 and 3 are epsilon-bromo aldehydes substituted with alpha,beta-unsaturated ester and oxime ether functions as radical traps, respectively. The tributyltin hydride mediated ring closure of these radical precursors have afforded a series of interesting, diverse and highly functionalized carbocycles which can be considered useful building blocks for the synthesis of branched-chain cyclitols, aminocyclitols and aminoconduritols. In these processes, a good chemical yield and high stereoselectivity has been found in the newly formed stereocenters. Particularly interesting has been the finding that the stereochemical outcome of the free-radical cyclization is independent of the ratio of isomers (E or Z) in oxime ether 3. These results show the power and the state of art of this strategy for the stereocontrolled synthesis of enantiomerically pure inositols from carbohydrates.

Application of meta- and para- phenylenediamine as enhanced oxime ligation catalysts for protein labeling, PEGylation, immobilization and release

PubMed Central

Mahmoodi, Mohammad M.; Rashidian, Mohammad; Zhang, Yi; Distefano, Mark D.

2015-01-01

Meta- and para- phenylenediamines have recently been shown to catalyze oxime and hydrazone ligation reactions at rates much faster than aniline, a commonly used catalyst. Here, it is demonstrated how these new catalysts can be used in a generally applicable procedure for fluorescent labeling, PEGylation, immobilization and release of aldehyde and ketone functionalized proteins. The chemical orthogonality of phenylenediamine-catalyzed oxime ligation versus copper catalyzed click reaction has also been harnessed for simultaneous dual labeling of bifunctional proteins containing both aldehyde and alkyne groups in high yield. PMID:25640893

Efficacy of two anthelmintic treatments, spinosad/milbemycin oxime and ivermectin/praziquantel in dogs with natural Toxocara spp. infection.

PubMed

Heredia Cardenas, Rafael; Romero Núñez, Camilo; Miranda Contreras, Laura

2017-11-30

Toxocara canis is one of the most important zoonotic parasites of dogs. The aim of the present study was to compare the efficacy of spinosad/milbemycin oxime and ivermectin/praziquantel in dogs naturally infected with Toxocara spp. We studied 200 dogs with a positive diagnosis of Toxocara spp. Through coproparasitoscopic analysis, two study groups of 100 dogs each were assigned: spinosad/milbemycin oxime at a dose of 30-60mg/kg and 0.75-1.0mg/kg, respectively, or ivermectin/praziquantel administered at a dose of 0.2mg/kg and 5mg/kg, respectively. Both groups received a single dose. Three stool samples, one at day 0 before treatment, and at 14 and 28days post-treatment were examined using concentration-flotation techniques. In both treatments, the number of Toxocara spp. eggs decreased; with spinosad/milbemycin oxime treatment, eggs decreased by 87% at 14days (P=0.008) and 94% at 28days after treatment, compared with 71% at day 14 and 88% at day 28 in dogs medicated with ivermectin/praziquantel. The spinosad/milbemycin oxime treated group showed a greater decrease in the number of Toxocara spp. positive dogs compared to the group receiving ivermectin/praziquantel. Copyright © 2017 Elsevier B.V. All rights reserved.

Oxidation of primary amines to oximes with molecular oxygen using 1,1-diphenyl-2-picrylhydrazyl and WO3/Al2O3 as catalysts.

PubMed

Suzuki, Ken; Watanabe, Tomonari; Murahashi, Shun-Ichi

2013-03-15

The oxidative transformation of primary amines to their corresponding oximes proceeds with high efficiency under molecular oxygen diluted with molecular nitrogen (O2/N2 = 7/93 v/v, 5 MPa) in the presence of the catalysts 1,1-diphenyl-2-picrylhydrazyl (DPPH) and tungusten oxide/alumina (WO3/Al2O3). The method is environmentally benign, because the reaction requires only molecular oxygen as the terminal oxidant and gives water as a side product. Various alicyclic amines and aliphatic amines can be converted to their corresponding oximes in excellent yields. It is noteworthy that the oxidative transformation of primary amines proceeds chemoselectively in the presence of other functional groups. The key step of the present oxidation is a fast electron transfer from the primary amine to DPPH followed by proton transfer to give the α-aminoalkyl radical intermediate, which undergoes reaction with molecular oxygen and hydrogen abstraction to give α-aminoalkyl hydroperoxide. Subsequent reaction of the peroxide with WO3/Al2O3 gives oximes. The aerobic oxidation of secondary amines gives the corresponding nitrones. Aerobic oxidative transformation of cyclohexylamines to cyclohexanone oximes is important as a method for industrial production of ε-caprolactam, a raw material for Nylon 6.

Synthesis of functionalized imidazolidine-2-thiones via NHC/base-promoted aza-benzoin/aza-acetalization domino reactions.

PubMed

Di Carmine, Graziano; Ragno, Daniele; De Risi, Carmela; Bortolini, Olga; Giovannini, Pier Paolo; Fantin, Giancarlo; Massi, Alessandro

2017-10-25

A strategy for the synthesis of biologically relevant 5-hydroxy-imidazolidine-2-thione derivatives is presented. A novel class of α-sulfonylamines have been suitably prepared (46-81% yield) as precursors of formal benzylidenethiourea acceptors; these are generated in situ and intercepted by N-heterocyclic carbene (NHC)-activated aldehydes affording open-chain aza-benzoin-type adducts, which in turn undergo an intramolecular aza-acetalization reaction in a one-pot fashion. A thiazolium salt/triethylamine couple proved to be the more effective system to trigger the domino sequence giving the target heterocycles in good yields (45-97%) and diastereoselectivities (up to 99 : 1 dr). The multigram scale synthesis and elaboration of a selected 5-hydroxy-imidazolidine-2-thione compound is also described.

N-silyl oxyketene imines are underused yet highly versatile reagents for catalytic asymmetric synthesis

NASA Astrophysics Data System (ADS)

Denmark, Scott E.; Wilson, Tyler W.

2010-11-01

The reactions of acyl anion equivalents (d1 synthons) with carbonyl electrophiles allow for the construction of a wide range of molecules useful for the synthesis of biologically active compounds, natural products and chiral ligands. Despite their utility, significant challenges still exist for developing catalytic, enantioselective variants of these reactions. For example, the asymmetric benzoin process, arguably the most characteristic reaction of d synthetic equivalents, finds no general solution for reactions involving aliphatic acyl anions. In this Article, we introduce a new class of stable, isolable silyl ketene imines derived from protected cyanohydrins. These nucleophiles serve as acyl anion equivalents in Lewis base catalysed aldol addition reactions and allow for the preparation of cross-benzoin and glycolate-aldol products in high yield and with exceptional diastereo- and enantioselectivities.

Study of molecular interactions in binary mixtures of 2-chloro-4'methoxy benzoin with various solvents through ultrasonic speed measurements

NASA Astrophysics Data System (ADS)

Thanuja, B.; Kanakam, C.; Nithya, G.

2013-12-01

Density ( ρ) and ultrasonic velocity ( U), for binary mixtures of 2-chloro-4'-methoxy benzoin with ethanol, chloroform, acetonitrile, benzene and 1,4-dioxane of different compositions have been measured at 298 K and explanation of solute solvent interactions and effect of polarity of the solvent on type of interactions are presented in this paper. From the above data, adiabatic compressibility ( β), intermolecular free length ( L f ) and relative association ( R A ) have been calculated. Other useful parameters such as excess density, excess velocity, excess intermolecular freelength and excess adiabatic compressibility have also been calculated. These parameters have been used to study the nature and extent of intermolecular interactions between component molecules in present binary mixtures.

Theoretical investigation on the chemoselective N-heterocyclic carbene-catalyzed cross-benzoin reactions.

PubMed

Liu, Tao; Han, Shu-Min; Han, Ling-Li; Wang, Lu; Cui, Xiang-Yang; Du, Chong-Yang; Bi, Siwei

2015-03-28

A density functional theory study was performed to understand the detailed mechanisms of the cross-benzoin reactions catalyzed by N-heterocyclic carbene (NHC) species. Our theoretical study predicted that the first H-transfer operates with water in solution as a mediator, and the second H-transfer undergoes a concerted mechanism rather than a stepwise one. In addition, the chemoselectivity of the reactions studied in this work has been explored. P1 was obtained as a major product mainly due to the more stable intermediate formed by reaction of NHC with reactant R1. Different steric effects resulting from the fused six-membered ring in transition state TS7 and the fused five-membered ring in transition state TS13 are the origin leading to the chemoselectivity.

Development and validation of a FIA/UV-vis method for pK(a) determination of oxime based acetylcholinesterase reactivators.

PubMed

Musil, Karel; Florianova, Veronika; Bucek, Pavel; Dohnal, Vlastimil; Kuca, Kamil; Musilek, Kamil

2016-01-05

Acetylcholinesterase reactivators (oximes) are compounds used for antidotal treatment in case of organophosphorus poisoning. The dissociation constants (pK(a1)) of ten standard or promising acetylcholinesterase reactivators were determined by ultraviolet absorption spectrometry. Two methods of spectra measurement (UV-vis spectrometry, FIA/UV-vis) were applied and compared. The soft and hard models for calculation of pK(a1) values were performed. The pK(a1) values were recommended in the range 7.00-8.35, where at least 10% of oximate anion is available for organophosphate reactivation. All tested oximes were found to have pK(a1) in this range. The FIA/UV-vis method provided rapid sample throughput, low sample consumption, high sensitivity and precision compared to standard UV-vis method. The hard calculation model was proposed as more accurate for pK(a1) calculation. Copyright © 2015 Elsevier B.V. All rights reserved.

Oxime-based linker libraries as a general approach for the rapid generation and screening of multidentate inhibitors

PubMed Central

Bahta, Medhanit; Liu, Fa; Kim, Sung-Eun; Stephen, Andrew G.; Fisher, Robert J.; Burke, Terrence R.

2013-01-01

The described oxime-based library protocol provides detailed procedures for the linkage of aminooxy functionality with aldehyde building blocks that result in the generation of libraries of multidentate inhibitors. Synthesis of inhibitors for protein tyrosine phosphatases (PTPs) and antagonists directed against the human tumor susceptibility gene 101 (Tsg101) are shown as examples. Three steps are involved: a) the design and synthesis of aminooxy platforms; b) tethering with aldehydes to form oxime-based linkages with sufficient purity; and c) direct in vitro biological evaluation of oxime products without purification. Each coupling reaction is a) performed in capped microtubes at room temperature; b) diluted for inhibitory evaluation and c) screened with targets in microplates to provide IC50 or Kd values. The synthesis of the aminooxy platforms takes 3–5 days; tethering with the aldehydes takes 24 h; and inhibition assay of enzymes and protein-protein interactions (PPIs) takes 30 min and 2 h respectively. PMID:22422315

O2 Activation and Double C-H Oxidation by a Mononuclear Manganese(II) Complex.

PubMed

Deville, Claire; Padamati, Sandeep K; Sundberg, Jonas; McKee, Vickie; Browne, Wesley R; McKenzie, Christine J

2016-01-11

A Mn(II) complex, [Mn(dpeo)2](2+) (dpeo=1,2-di(pyridin-2-yl)ethanone oxime), activates O2, with ensuing stepwise oxidation of the methylene group in the ligands providing an alkoxide and ultimately a ketone group. X-ray crystal-structure analysis of an intermediate homoleptic alkoxide Mn(III) complex shows tridentate binding of the ligand via the two pyridyl groups and the newly installed alkoxide moiety, with the oxime group no longer coordinated. The structure of a Mn(II) complex of the final ketone ligand, cis-[MnBr2(hidpe)2] (hidpe=2-(hydroxyimino)-1,2-di(pyridine-2-yl)ethanone) shows that bidentate oxime/pyridine coordination has been resumed. H2(18)O and (18)O2 labeling experiments suggest that the inserted O atoms originate from two different O2 molecules. The progress of the oxygenation was monitored through changes in the resonance-enhanced Raman bands of the oxime unit. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photosensitized regeneration of carbonyl compounds from oximes.

PubMed

de Lijser, H J Peter; Fardoun, Fadia H; Sawyer, Jody R; Quant, Michelle

2002-07-11

[reaction: see text] Deprotection of oximes to their corresponding carbonyl compounds through the use of photosensitized electron-transfer reactions proceeds in reasonable to good yields. Better yields are obtained in nonpolar solvents and when triplet sensitizers are used. Preliminary mechanistic studies suggest the involvement of an iminoxyl radical.

Interactions of vanadium( iv ) with amidoxime ligands: redox reactivity

DOE PAGES

Parker, B. F.; Hohloch, S.; Pankhurst, J. R.; ...

2018-01-01

Vanadium is the main competitor for uranium extraction from seawater, and V( iv ) comprises a minor but important portion of this. V( iv ) undergoes redox reactions with oximes and amidoxime ligands under seawater-relevant conditions, leading to V( v ) complexes and loss of oxime functional groups.

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

Worek, Franz, E-mail: franzworek@bundeswehr.org; Wille, Timo; Aurbek, Nadine

Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary highmore » MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning.« less

10th International Meeting on Cholinesterases

DTIC Science & Technology

2009-10-01

NATIVE, PHOSPHYLATED AND AGED HUMAN ACETYLCHOLINESTERASE AND BUTYRYLCHOLINESTERASE Page 9 Zrinka Kovarik ( Zagreb , Croatia): OXIME-ASSISTED...REACTIVATION OF PHOSPHORYLATED BUTYRYLCHOLINESTERASE Goran Šinko ( Zagreb , Croatia): INTERACTIONS OF PYRIDINIUM OXIMES WITH ACETYLCHOLINESTERASE...OF CHOLINESTERASES IN THE BRAIN Ninoslav Mimica ( Zagreb , Croatia): THE CHOLINESTERASE INHIBITORS – CURRENT CLINICAL VIEW AND CROATIAN REALITY

Alkyl group substitution by oxime-bound palladium(II) (the Shaw reaction): Alkly group selectivity and deuterium isotope effects

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

Wells, A.P.; Kitching, W.

1992-08-01

This report provides information regarding the selectivity of alkyl groups and the nature of the transition state for C-H palladation by oxime-bound palladium(II) (the Shaw reaction). The kinetic deuterium isotope effects are also presented. 21 refs.

Organic Process Technology Valuation: Cyclohexanone Oxime Syntheses

ERIC Educational Resources Information Center

Cannon, Kevin C.; Breen, Maureen P.

2010-01-01

Three contemporary processes for cyclohexanone oxime synthesis are evaluated in a case study. The case study introduces organic chemistry students to basic cost accounting to determine the most economical technology. Technical and financial aspects of these processes are evaluated with problem-based exercises that may be completed by students…

Transacylation and Transamidation Reactions in Neat and Dissolved Systems.

DTIC Science & Technology

reaction of non-cyclic carboxy anhydrides with amides and specifically acetanilide has been studied. Preliminary results of the kinetic studies of the reaction of organic bromides with benzoin are reported. (Author)

Intramolecular Benzoin Reaction Catalyzed by Benzaldehyde Lyase from Pseudomonas Fluorescens Biovar I.

PubMed

Hernández, Karel; Parella, Teodor; Petrillo, Giovanna; Usón, Isabel; Wandtke, Claudia M; Joglar, Jesús; Bujons, Jordi; Clapés, Pere

2017-05-02

Intramolecular benzoin reactions catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I (BAL) are reported. The structure of the substrates envisaged for this reaction consists of two benzaldehyde derivatives linked by an alkyl chain. The structural requirements needed to achieve the intramolecular carbon-carbon bond reaction catalyzed by BAL were established. Thus, a linker consisting of a linear alkyl chain of three carbon atoms connected through ether-type bonds to the 2 and 2' positions of two benzaldehyde moieties, which could be substituted with either Cl, Br, or OCH 3 at either the 3 and 3' or 5 and 5' positions, were suitable substrates for BAL. Reactions with 61-84 % yields of the intramolecular product and ee values between 64 and 98 %, were achieved. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Calorimetric indications of a cooperativity onset in the crossover region of dynamic glass transition for benzoin isobutylether

NASA Astrophysics Data System (ADS)

Kahle, S.; Schröter, K.; Hempel, E.; Donth, E.

1999-10-01

Heat capacity spectroscopy (HCS), dielectric spectroscopy, and shear viscosity data are reported for liquid benzoin isobutylether (BIBE). Dielectric and viscosity peculiarities indicate the crossover region of dynamic glass transition at T=(-8±8) °C where the extrapolated Johari Goldstein β relaxation intersects the main transition trace in an Arrhenius plot. Although HCS does not reach the crossover frequency of order ω=2×106 rad/s, the linear decrease of the square root of cooperativity as calculated from HCS data at lower frequencies indicates a cooperativity onset in the crossover temperature-frequency range. As BIBE belongs to another dielectric crossover scenario as the substances where such an onset could previously be observed, it seems that the cooperativity onset is a general property of the crossover region.

Ultrasonic studies of intermolecular interactions in binary mixtures of 4-methoxy benzoin with various solvents: Excess molar functions of ultrasonic parameters at different concentrations and in different solvents.

PubMed

Thanuja, B; Nithya, G; Kanagam, Charles C

2012-11-01

Density (ρ), ultrasonic velocity (U), for the binary mixtures of 4-methoxy benzoin (4MB) with ethanol, chloroform, acetonitrile, benzene, and di-oxane were measured at 298K. The solute-solvent interactions and the effect of the polarity of the solvent on the type of intermolecular interactions are discussed here. From the above data, adiabatic compressibility (β), intermolecular free length (L(f)), acoustic impedance (Z), apparent molar volume (Ø), relative association (RA) have been calculated. Other useful parameters such as excess density, excess velocity and excess adiabatic compressibility have also been calculated. These parameters were used to study the nature and extent of intermolecular interactions between component molecules in the binary mixtures. Copyright © 2012 Elsevier B.V. All rights reserved.

THE PRODUCTS OF THE CYCLIZING DEHYDRATION OF 1-BETA-PHENYLETHYLCYCLOHEXANOL-1 AND THE SYNTHESIS OF SPIROCYCLOHEXANE-1,1-INDANONE-3.

PubMed

Levitz, M; Perlman, D; Bogert, M T

1939-08-04

(1) Spirocyclohexane-1,1-indanone (VI) has been found among the oxidation products of the hydrocarbon mixture which results when 1-beta-phenylethylcyclohexanol-1 is dehydrated, or when 1-beta-phenylethylcyclohexene is cyclized by aluminum trichloride, and its constitution has been proved by synthesis (2) Its oxime melts at 137-137.8 degrees (corr.). The oxime of m.p. 187.5 degrees , reported by Cook et al. therefore must be derived from some other ketone, perhaps the trans-ketoöctahydrophenanthrene, since we were unable to isolate any oxime of m.p. 177 degrees , the figure which they reported for this compound.

Theoretical NMR and conformational analysis of solvated oximes for organophosphates-inhibited acetylcholinesterase reactivation

NASA Astrophysics Data System (ADS)

da Silva, Jorge Alberto Valle; Modesto-Costa, Lucas; de Koning, Martijn C.; Borges, Itamar; França, Tanos Celmar Costa

2018-01-01

In this work, quaternary and non-quaternary oximes designed to bind at the peripheral site of acetylcholinesterase previously inhibited by organophosphates were investigated theoretically. Some of those oximes have a large number of degrees of freedom, thus requiring an accurate method to obtain molecular geometries. For this reason, the density functional theory (DFT) was employed to refine their molecular geometries after conformational analysis and to compare their 1H and 13C nuclear magnetic resonance (NMR) theoretical signals in gas-phase and in solvent. A good agreement with experimental data was achieved and the same theoretical approach was employed to obtain the geometries in water environment for further studies.

21 CFR 520.1447 - Milbemycin oxime, lufenuron, and praziquantel tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...) Amount. 0.5 mg milbemycin oxime, 10 mg lufenuron, and 5 mg of praziquantel per kilogram of body weight, once a month. (ii) Indications for use. For the prevention of heartworm disease caused by Dirofilaria...

21 CFR 520.1447 - Milbemycin oxime, lufenuron, and praziquantel tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...) Amount. 0.5 mg milbemycin oxime, 10 mg lufenuron, and 5 mg of praziquantel per kilogram of body weight, once a month. (ii) Indications for use. For the prevention of heartworm disease caused by Dirofilaria...

21 CFR 520.1447 - Milbemycin oxime, lufenuron, and praziquantel tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...) Amount. 0.5 mg milbemycin oxime, 10 mg lufenuron, and 5 mg of praziquantel per kilogram of body weight, once a month. (ii) Indications for use. For the prevention of heartworm disease caused by Dirofilaria...

Phenanthridine synthesis through iron-catalyzed intramolecular N-arylation of O-acetyl oxime.

PubMed

Deb, Indubhusan; Yoshikai, Naohiko

2013-08-16

O-Acetyl oximes derived from 2'-arylacetophenones undergo N-O bond cleavage/intramolecular N-arylation in the presence of a catalytic amount of iron(III) acetylacetonate in acetic acid. In combination with the conventional cross-coupling or directed C-H arylation, the reaction offers a convenient route to substituted phenanthridines.

Changes of rat plasma total low molecular weight antioxidant level after tabun exposure and consequent treatment by acetylcholinesterase reactivators.

PubMed

Pohanka, Miroslav; Karasova, Jana Zdarova; Musilek, Kamil; Kuca, Kamil; Jung, Young-Sik; Kassa, Jiri

2011-02-01

These experiments were performed on a rat model. The rats were divided into eight groups and consequently exposed to either a saline solution (control), atropine or a combination of atropine and tabun. The reactivation efficacy of the oximes was estimated on the rats exposed to tabun, atropine and a reactivator of AChE. The oximes HI-6, obidoxime, trimedoxime, K203 and KR-22836 were used as representative compounds of commonly available and new AChE reactivators. Besides the positive effect of the administered reactivators on blood AChE activity, the sizable modulation of low molecular weight antioxidant (LMWA) levels was also determined. The LMWA levels in the the animals treated with the oxime reactivators were decreased in comparison with the animals treated by atropine alone. It was found that the levels of LMWA returned to the level found in the control animals when either trimedoxime, K203 or KR-22836 were administered. The principle of oxime reactivator function and a novel insight into AChE activity regulation and oxidative stress is discussed.

Synthesis, structural characterization and dielectric behavior of new oxime-cyclotriphosphazene derivatives

NASA Astrophysics Data System (ADS)

Koran, Kenan; Özen, Furkan; Biryan, Fatih; Görgülü, Ahmet Orhan

2016-02-01

The cyclotriphosphazene compound (2) bearing formyl groups as side groups was obtained from the reaction of 2,2-Dichloro-4,4,6,6-bis[spiro(2‧,2″-dioxy-1‧,1″-biphenylyl)]cyclotriphosphazene (1) with 4-hydroxy-3-methoxybenzaldehyde in the presence K2CO3 in tetrahydrofuran. Oxime-cyclotriphosphazene compound (3) was synthesized from the reaction of compound 2 with hydroxylamine hydrochloride in pyridine. The synthesized oxime-phosphazene compound (3) was reacted with alkyl and acyl halides. As a results, the cyclotriphosphazene compounds (1-10) bearing oxime ether and ester as side groups were obtained. The chemical structures of these compounds (1-10) were determined by elemental analysis, FT-IR, 1H, 13C and 31P NMR spectroscopic methods. Dielectric constant, dielectric loss factors and conductivity properties of cyclotriphosphazene compounds were measured over the frequency range from 100 Hz to 2 kHz at 25 °C and compared with each other. It is found that ester substituted cyclotriphosphazenes have higher dielectric constant. Our study suggests that these phosphazenes promising candidate materials in multifunctional optoelectronic devices.

Oxime amides as a novel zinc binding group in histone deacetylase inhibitors: synthesis, biological activity, and computational evaluation.

PubMed

Botta, Cinzia B; Cabri, Walter; Cini, Elena; De Cesare, Lucia; Fattorusso, Caterina; Giannini, Giuseppe; Persico, Marco; Petrella, Antonello; Rondinelli, Francesca; Rodriquez, Manuela; Russo, Adele; Taddei, Maurizio

2011-04-14

Several oxime containing molecules, characterized by a SAHA-like structure, were explored to select a potentially new biasing binding element for the zinc in HDAC catalytic site. All compounds were evaluated for their in vitro inhibitory activity against the 11 human HDACs isoforms. After identification of a "hit" molecule, a programmed variation at the cap group and at the linker was carried out in order to increase HDAC inhibition and/or paralogue selectivity. Some of the new derivatives showed increased activity against a number of HDAC isoforms, even if their overall activity range is still far from the inhibition values reported for SAHA. Moreover, different from what was reported for their hydroxamic acid analogues the new α-oxime amide derivatives do not select between class I and class II HDACs; rather they target specific isoforms in each class. These somehow contradictory results were finally rationalized by a computational assisted SAR, which gave us the chance to understand how the oxime derivatives interact with the catalytic site and justify the observed activity profile.

Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review.

PubMed

Sharma, Rahul; Gupta, Bhanushree; Singh, Namrata; Acharya, J R; Musilek, Kamil; Kuca, Kamil; Ghosh, Kallol Kumar

2015-01-01

Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam) and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.

Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: a modified kinetic approach.

PubMed

Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

2010-12-15

Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning. Copyright © 2010 Elsevier Inc. All rights reserved.

Milbemycins: More than Efflux Inhibitors for Fungal Pathogens

PubMed Central

Silva, Luis Vale; Sanguinetti, Maurizio; Vandeputte, Patrick; Torelli, Riccardo; Rochat, Bertrand

2013-01-01

Existing antifungal agents are still confronted to activities limited to specific fungal species and to the development of resistance. Several improvements are possible either by tackling and overcoming resistance or exacerbating the activity of existing antifungal agents. In Candida glabrata, azole resistance is almost exclusively mediated by ABC transporters (including C. glabrata CDR1 [CgCDR1] and CgCDR2) via gain-of-function mutations in the transcriptional activator CgPDR1 or by mitochondrial dysfunctions. We also observed that azole resistance was correlating with increasing virulence and fitness of C. glabrata in animal models of infection. This observation motivated the re-exploitation of ABC transporter inhibitors as a possible therapeutic intervention to decrease not only the development of azole resistance but also to interfere with the virulence of C. glabrata. Milbemycins are known ABC transporter inhibitors, and here we used commercially available milbemycin A3/A4 oxim derivatives to verify this effect. As expected, the derivatives were inhibiting C. glabrata efflux with the highest activity for A3 oxim below 1 μg/ml. More surprising was that oxim derivatives had intrinsic fungicidal activity above 3.2 μg/ml, thus highlighting effects additional to the efflux inhibition. Similar values were obtained with C. albicans. Our data show that the fungicidal activity could be related to reactive oxygen species formation in these species. Transcriptional analysis performed both in C. glabrata and C. albicans exposed to A3 oxim highlighted a core of commonly regulated genes involved in stress responses, including genes involved in oxidoreductive processes, protein ubiquitination, and vesicle trafficking, as well as mitogen-activated protein kinases. However, the transcript profiles contained also species-specific signatures. Following these observations, experimental treatments of invasive infections were performed in mice treated with the commercial A3/A4 oxim preparation alone or in combination with fluconazole. Tissue burden analysis revealed that oxims on their own were able to decrease fungal burdens in both Candida species. In azole-resistant isolates, oxims acted synergistically in vivo with fluconazole to reduce fungal burden to levels of azole-susceptible isolates. In conclusion, we show here the potential of milbemycins not only as drug efflux inhibitors but also as effective fungal growth inhibitors in C. glabrata and C. albicans. PMID:23208712

Can hydroxylamine be a more potent nucleophile for the reactivation of tabun-inhibited AChE than prototype oxime drugs? An answer derived from quantum chemical and steered molecular dynamics studies.

PubMed

Lo, Rabindranath; Ganguly, Bishwajit

2014-07-29

Organophosphorus nerve agents are highly toxic compounds which strongly inhibit acetylcholinesterase (AChE) in the blood and in the central nervous system (CNS). Tabun is one of the highly toxic organophosphorus (OP) compounds and is resistant to many oxime drugs formulated for the reactivation of AChE. The reactivation mechanism of tabun-conjugated AChE with various drugs has been examined with density functional theory and ab initio quantum chemical calculations. The presence of a lone-pair located on the amidic group resists the nucleophilic attack at the phosphorus center of the tabun-conjugated AChE. We have shown that the newly designed drug candidate N-(pyridin-2-yl)hydroxylamine, at the MP2/6-31+G*//M05-2X/6-31G* level in the aqueous phase with the polarizable continuum solvation model (PCM), is more effective in reactivating the tabun-conjugated AChE than typical oxime drugs. The rate determining activation barrier with N-(pyridin-2-yl)hydroxylamine was found to be ∼1.7 kcal mol(-1), which is 7.2 kcal mol(-1) lower than the charged oxime trimedoxime (one of the most efficient reactivators in tabun poisonings). The greater nucleophilicity index (ω(-)) and higher CHelpG charge of pyridinylhydroxylamine compared to TMB4 support this observation. Furthermore, we have also examined the reactivation process of tabun-inhibited AChE with some other bis-quaternary oxime drug candidates such as methoxime (MMB4) and obidoxime. The docking analysis suggests that charged bis-quaternary pyridinium oximes have greater binding affinity inside the active-site gorge of AChE compared to the neutral pyridinylhydroxylamine. The peripheral ligand attached to the neutral pyridinylhydroxylamine enhanced the binding with the aromatic residues in the active-site gorge of AChE through effective π-π interactions. Steered molecular dynamics (SMD) simulations have also been performed with the charged oxime (TMB4) and the neutral hydroxylamine. From protein-drug interaction parameters (rupture force profiles, hydrogen bonds, hydrophobic interactions), geometry and the orientation of the drug candidates, the hydroxylamine is suggested to orchestrate the reactivation process better than TMB4. Furthermore, the calculated log P values show the effective penetration of the neutral drug candidate through the blood-brain barrier. The toxicity measurements and the IC50 values (a measure of the intrinsic affinity toward AChE) suggest that the pyridinylhydroxylamine compound could have similar toxic behavior compared to the prototype oxime antidotes used for reactivation purposes. The newly designed pyridinylhydroxylamine drug candidate can be an effective antidote both kinetically and structurally to reactivate the tabun-inhibited enzyme.

Green chiral HPLC enantiomeric separations using high temperature liquid chromatography and subcritical water on Chiralcel OD and Chiralpak AD.

PubMed

Droux, Serge; Félix, Guy

2011-01-01

We report here the application of subcritical water in chiral separations on two popular polysaccharide chiral stationary phases (CSPs): Chiralpak AD and Chiralcel OD. The behavior of these two CSPs was studied under reversed phase conditions at room temperature to discover the maximum percentage of water in the mobile phase, which provided the separation of enantiomers of flavanone and benzoin, respectively, in a reasonable time (i.e., less than 1 h). Then, the stability of Chiralpak AD and Chiralcel OD versus temperature was investigated and discussed. Chiralcel OD separation of flavanone racemate was obtained at 120 °C with water and 2-propanol (80/20) as the mobile phase, while benzoin racemate was separated in pure water at 160 °C. Separations of several racemates were also presented, and advantages and limitations of the technique were discussed. Copyright © 2011 Wiley Periodicals, Inc.

Ultrasonic evidence of hydrophobic interactions. Effect of ultrasound on benzoin condensation and some other reactions in aqueous ethanol.

PubMed

Tuulmets, Ants; Hagu, Hannes; Salmar, Siim; Cravotto, Giancarlo; Järv, Jaak

2007-03-29

The kinetics of KCN-catalyzed benzoin condensation of benzaldehyde in water and ethanol-water binary mixtures was investigated both under ultrasound at 22 kHz and without sonication. Thermodynamic activation parameters were calculated from kinetic data obtained at 35, 50, and 65 degrees C. Evidence that ultrasound can retard reactions is reported and hence a direct proof that sonochemical processes occur in the bulk solution. Former results and literature data for ester hydrolyses and tert-butyl chloride solvolysis are involved in the discussion. A quantitative relationship between sonication effects and the hydrophobicity of reagents is presented for the first time. Ultrasound affects hydrophobic interactions with the solvent, which are not manifested in conventional kinetics. When it suppresses the stabilization of the encounter complexes between reagents, sonication hinders the reaction but accelerates it when it perturbs the hydrophobic stabilization of the ground state of a reagent.

Spectrofluorimetric analysis of famotidine in pharmaceutical preparations and biological fluids by derivatization with benzoin

NASA Astrophysics Data System (ADS)

Alamgir, Malik; Khuhawar, Muhammad Yar; Memon, Saima Q.; Hayat, Amir; Zounr, Rizwan Ali

2015-01-01

A sensitive and simple spectrofluorimetric method has been developed for the analysis of famotidine, from pharmaceutical preparations and biological fluids after derivatization with benzoin. The reaction was carried out in alkaline medium with measurement of fluorescence intensity at 446 nm with excitation wavelength at 286 nm. Linear calibration was obtained with 0.5-15 μg/ml with coefficient of determination (r2) 0.997. The factors affecting the fluorescence intensity were optimized. The pharmaceutical additives and amino acid did not interfere in the determination. The mean percentage recovery (n = 4) calculated by standard addition from pharmaceutical preparation was 94.8-98.2% with relative standard deviation (RSD) 1.56-3.34% and recovery from deproteinized spiked serum and urine of healthy volunteers was 98.6-98.9% and 98.0-98.4% with RSD 0.34-0.84% and 0.29-0.87% respectively.

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification.

PubMed

Zaghi, Anna; Ragno, Daniele; Di Carmine, Graziano; De Risi, Carmela; Bortolini, Olga; Giovannini, Pier Paolo; Fantin, Giancarlo; Massi, Alessandro

2016-01-01

A convenient heterogeneous continuous-flow procedure for the polarity reversal of aromatic α-diketones is presented. Propaedeutic batch experiments have been initially performed to select the optimal supported base capable to initiate the two electron-transfer process from the carbamoyl anion of the N , N -dimethylformamide (DMF) solvent to the α-diketone and generate the corresponding enediolate active species. After having identified the 2- tert -butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine on polystyrene (PS-BEMP) as the suitable base, packed-bed microreactors (pressure-resistant stainless-steel columns) have been fabricated and operated to accomplish the chemoselective synthesis of aroylated α-hydroxy ketones and 2-benzoyl-1,4-diones (benzoin- and Stetter-like products, respectively) with a good level of efficiency and with a long-term stability of the packing material (up to five days).

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

PubMed Central

Zaghi, Anna; Ragno, Daniele; Di Carmine, Graziano; De Risi, Carmela; Bortolini, Olga; Giovannini, Pier Paolo; Fantin, Giancarlo

2016-01-01

A convenient heterogeneous continuous-flow procedure for the polarity reversal of aromatic α-diketones is presented. Propaedeutic batch experiments have been initially performed to select the optimal supported base capable to initiate the two electron-transfer process from the carbamoyl anion of the N,N-dimethylformamide (DMF) solvent to the α-diketone and generate the corresponding enediolate active species. After having identified the 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine on polystyrene (PS-BEMP) as the suitable base, packed-bed microreactors (pressure-resistant stainless-steel columns) have been fabricated and operated to accomplish the chemoselective synthesis of aroylated α-hydroxy ketones and 2-benzoyl-1,4-diones (benzoin- and Stetter-like products, respectively) with a good level of efficiency and with a long-term stability of the packing material (up to five days). PMID:28144342

Mechanism of α-ketol-type rearrangement of benzoin derivatives under basic conditions.

PubMed

Karino, Masahiro; Kubouchi, Daiki; Hamaoka, Kazuki; Umeyama, Shintaro; Yamataka, Hiroshi

2013-07-19

The mechanism of base-catalyzed rearrangement of ring-substituted benzoins in aqueous methanol was examined by kinetic and product analyses. Substituent effects on the rate and equilibrium constants revealed that the kinetic process has a different electron demand compared to the equilibrium process. Reactions in deuterated solvents showed that the rate of H/D exchange of the α-hydrogen is similar to the overall rate toward the equilibrium state. A proton-inventory experiment using partially deuterated solvents showed a linear dependence of the rate on the deuterium fraction of the solvent, indicating that only one deuterium isotope effect contributes to the overall rate process. All these results point to a mechanism in which the rearrangement is initiated by the rate-determining α-hydrogen abstraction rather than a mechanism with initial hydroxyl hydrogen abstraction as in the general α-ketol rearrangement.

Severe facial dermatitis as a late complication of aesthetic rhinoplasty; a case report

PubMed Central

Rajabian, Mohammad Hossain; Sodaify, Manoochehr; Aghaei, Shahin

2004-01-01

Background Contact dermatitis, as a cutaneous complication after rhinoplasty, is of early onset, limited and transient. The cause of this dermatitis is irritant or allergic. Late onset skin complications are rare and non-inflammatory. Case presentation We are reporting an unexpected, severe allergic contact dermatitis of the face, in a young female, appearing one month following aesthetic rhinoplasty. She failed to respond to ordinary treatments for dermatitis. We did standard battery – including nitrofurazone, tincture of benzoin and hydrocortisone – patch test for the patient that showed sensitivity to benzoin and corticosteroid. Conclusions In summary we report a case of a severe allergic contact dermatitis of the face, in a 21-year-old girl who underwent corrective aesthetic rhinoplasty, appearing one month following surgical operation. We were unable to find a similar report in the medical literature. PMID:15056395

21 CFR 520.1445 - Milbemycin oxime and praziquantel.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Section 520.1445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... orally, once a month, a minimum dosage of 0.23 mg per pound (mg/lb) of body weight (0.5 mg per kilogram (mg/kg)) milbemycin oxime and 2.28 mg/lb of body weight (5 mg/kg) praziquantel. (ii) Indications for...

21 CFR 520.1445 - Milbemycin oxime and praziquantel.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Section 520.1445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... orally, once a month, a minimum dosage of 0.23 mg per pound (mg/lb) of body weight (0.5 mg per kilogram (mg/kg)) milbemycin oxime and 2.28 mg/lb of body weight (5 mg/kg) praziquantel. (ii) Indications for...

Construction of Benzene Rings by Copper-Catalyzed Cycloaddition Reactions of Oximes and Maleimides: An Access to Fused Phthalimides.

PubMed

Yang, Jie; Zhao, Bo; Xi, Yue; Sun, Si; Yang, Zhen; Ye, Ying; Jiang, Kun; Wei, Ye

2018-02-16

A useful Cu-catalyzed cycloaddition protocol for the construction of benzene rings has been achieved. The reactions, utilizing readily available oximes and maleimides as starting materials, proceed under mild reaction conditions to generate a series of structurally interesting fused-phthalimides that are difficult to be prepared by conventional methods.

Transition Metal Free Multicomponent approach to Stereo-enriched Cyclopentyl-isoxazoles via C-C Bond Cleavage.

PubMed

Kaliappan, Krishna Pillai; Subramanian, Parthasarathi

2018-06-19

An efficient multicomponent reaction leading to the synthesis of stereo-enriched cyclopentyl-isoxazoles from camphor derived α-oxime, alkynes and MeOH is reported. Our method involves a series of cascade transformations such as in situ generation of catalyst I(III) which catalyzes the addition MeOH into a sterically hindered ketone, oxime oxidation and α-hydroxyiminium ion rearrangement to generate in situ nitrile oxide which upon [3+2]-cycloaddition reaction with alkynes delivers regioselective products. The reaction is very selective to syn-oxime. This multicomponent approach has also been extended for the synthesis of a novel glycoconjugate, camphoric ester-isoxazole C-galactoside. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Coumarin-Based Oxime Esters: Photobleachable and Versatile Unimolecular Initiators for Acrylate and Thiol-Based Click Photopolymerization under Visible Light-Emitting Diode Light Irradiation.

PubMed

Li, Zhiquan; Zou, Xiucheng; Zhu, Guigang; Liu, Xiaoya; Liu, Ren

2018-05-09

Developing efficient unimolecular visible light-emitting diode (LED) light photoinitiators (PIs) with photobleaching capability, which are essential for various biomedical applications and photopolymerization of thick materials, remains a great challenge. Herein, we demonstrate the synthesis of a series of novel PIs, containing coumarin moieties as chromophores and oxime ester groups as initiation functionalities and explore their structure-activity relationship. The investigated oxime esters can effectively induce acrylates and thiol-based click photopolymerization under 450 nm visible LED light irradiation. The initiator O-3 exhibited excellent photobleaching capability and enabled photopolymerization of thick materials (∼4.8 mm). The efficient unimolecular photobleachable initiators show great potential in dental materials and 3D printings.

Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis.

PubMed

Battaglia, Alex; Nguyen, Thanh

2017-12-01

The aim of this study was to test the hypothesis that tincture of benzoin (TOB) facilitates immediate transmucosal nicotine absorption while simultaneously promoting a safe and sustained delivery of the nicotine. In combination with TOB, nicotine toxicity and diffusion across human mucosal cells were measured using a 3-D human mucosal tissue model. Nicotine was delivered 2.1 times more quickly in combination with TOB than in combination with saline (p < 0.05). Despite the increased diffusion, nicotine in combination with TOB significantly increased mucosal cell survival (p < 0.05) by reducing the release of mitochondrial cytochrome c into the cytoplasm when compared with nicotine without TOB. The average percentage distribution of cytochrome c in the cytosolic fraction over time of nicotine + 79% ethyl alcohol (ETOH) versus nicotine plus TOB (79% ETOH) was significantly different over 120 min (60.0 ± 29.9% cytosol, 16.1 ± 9.4% cytosol, p = 0.03). Related to the reduction of cytochrome c release into the cytoplasm, TOB suppressed caspase-3 and -9 activity, thereby preventing intrinsic apoptosis and providing cytoprotection of the mucosal cells (ETOH + nicotine vs ETOH + nicotine + TOB: p = 0.008 for caspase 3, p < 0.001 for caspase 9). Two hours of TOB (17-24% benzoin, 79% ETOH) plus nicotine promotes diffusion of nicotine across human mucosal cells and simultaneously prevents human mucosal cell toxicity by inhibiting cytochrome c release into the cytosol, thereby preventing caspase 3 and 9 activity and subsequent intrinsic apoptosis.

Reactivation of organophosphate-inhibited human acetylcholinesterase by isonitrosoacetone (MINA): a kinetic analysis.

PubMed

Worek, Franz; Thiermann, Horst

2011-11-15

Treatment of poisoning by highly toxic organophosphorus compounds (OP) with atropine and an acetylcholinesterase (AChE) reactivator (oxime) is of limited effectiveness in case of different nerve agents and pesticides. One challenge is the reactivation of OP-inhibited brain AChE which shows inadequate success with charged pyridinium oximes. Recent studies with high doses of the tertiary oxime isonitrosoacetone (MINA) indicated a beneficial effect on central and peripheral AChE and on survival in nerve agent poisoned guinea pigs. Now, an in vitro study was performed to determine the reactivation kinetics of MINA with tabun-, sarin-, cyclosarin-, VX- and paraoxon-inhibited human AChE. MINA showed an exceptionally low affinity to inhibited AChE but, with the exception of tabun-inhibited AChE, a moderate to high reactivity. In comparison to the pyridinium oximes obidoxime, 2-PAM and HI-6 the affinity and reactivity of MINA was in most cases lower and in relation to the most effective reactivators, the second order reactivation constant of MINA was 500 to 3400-fold lower. Hence, high in vivo MINA concentrations would be necessary to achieve at least partial reactivation. This assumption corresponds to in vivo data showing a dose-dependent effect on reactivation and survival in animals. In view, of the toxic potential of MINA in animals human studies would be necessary to determine the tolerability and pharmacokinetics of MINA in order to enable a proper assessment of the value of this oxime as an antidote in OP poisoning. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chromatographic analysis of toxic phosphylated oximes (POX): a brief overview.

PubMed

Becker, Christian; Worek, Franz; John, Harald

2010-10-01

Poisoning with organophosphorus compounds (OP), e.g. pesticides and nerve agents, causes inhibition of acetylcholinesterase (AChE) by phosphylation of the active site serine residue. Consequently, accumulation of stimulating acetylcholine in the synaptic cleft induces cholinergic crisis which ultimately may lead to death. For standard causal therapy, enzyme reactivators are administered representing oxime derivatives of quarternary pyridinium compounds, e.g. pralidoxime (2-PAM), obidoxime and HI 6. The mechanism of action includes removal of the phosphyl moiety by a nucleophilic attack of the oximate molecule substituting the enzyme and forming a phosphylated oxime (POX). POX is produced in stoichiometric amounts of reactivated enzyme and exhibits a significantly enhanced toxicity (inhibition rate constant) when compared to the parent OP. However, stability of POX under physiological conditions appears to be highly limited. Nevertheless, the presence of POX reveals a potential critical issue for both therapeutic efficacy in vivo and pharmacokinetic and pharmacodynamic (PK-PD) modelling based on cholinesterase activity data. Detailed characterization represents an important need for elaboration of the entire oxime pharmacology.Nevertheless, reports on POX toxicity and analysis are quite rare and may therefore be indicative of the challenge of POX analysis. This review provides a concise overview of chromatographic approaches applied to POX separation. Chromatography represents the key technology for POX purification and quantification in kinetic in vitro studies using buffers and biological fluids. Applications based on reversed-phase chromatography (RPC), ion pair chromatography (IPC) and an affinity approach as well as thin layer chromatography (TLC) are discussed and novel applications and data are presented. Copyright © 2010 John Wiley & Sons, Ltd.

40 CFR 721.6660 - Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of alkanepolyol and poly-alkyl... Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime-blocked... substance identified generically as a polymer of alkane-polyol and polyalkylpolyisocyanatocarbomonocy- cle...

40 CFR 721.6660 - Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymer of alkanepolyol and poly-alkyl... Polymer of alkanepolyol and poly-alkyl-poly-iso-cyan-ato-car-bo-mo-no-cycle, acetone oxime-blocked... substance identified generically as a polymer of alkane-polyol and polyalkylpolyisocyanatocarbomonocy- cle...

Iron-Catalyzed Intramolecular C(sp(2))-N Cyclization of 1-(N-Arylpyrrol-2-yl)ethanone O-Acetyl Oximes toward Pyrrolo[1,2-a]quinoxaline Derivatives.

PubMed

Zhang, Zhiguo; Li, Junlong; Zhang, Guisheng; Ma, Nana; Liu, Qingfeng; Liu, Tongxin

2015-07-02

An efficient and convenient iron-catalyzed protocol has been developed for the synthesis of substituted pyrrolo[1,2-a]quinoxalines from 1-(N-arylpyrrol-2-yl)ethanone O-acetyl oximes through N-O bond cleavage and intramolecular directed C-H arylation reactions in acetic acid.

Eco-friendly synthesis, physicochemical studies, biological assay and molecular docking of steroidal oxime-ethers

PubMed Central

Alam, Mahboob; Lee, Dong-Ung

2015-01-01

The aim of this study was to report the synthesis of biologically active compounds; 7-(2′-aminoethoxyimino)-cholest-5-ene (4), a steroidal oxime-ether and its derivatives (5, 6) via a facile microwave assisted solvent free reaction methodology. This new synthetic, eco-friendly, sustainable protocol resulted in a remarkable improvement in the synthetic efficiency (85-93 % yield) and high purity using basic alumina. The synthesized compounds were screened for their antibacterial against six bacterial strains by disc diffusion method and antioxidant potential by DPPH assay. The binding capabilities of a compound 6 exhibiting good antibacterial potential were assessed on the basis of molecular docking studies and four types of three-dimensional molecular field descriptors. Moreover the structure-antimicrobial activity relationships were studied using some physicochemical and quantum-chemical parameters with GAMESS interface as well as WebMO Job Manager by using the basic level of theory. Hence, this synthetic approach is believed to provide a better scope for the synthesis of steroidal oxime-ether analogues and will be a more practical alternative to the presently existing procedures. Moreover, detailed in silico docking studies suggested the plausible mechanism of steroidal oxime-ethers as effective antimicrobial agents. PMID:27330525

Insights into the mechanism and catalysis of oxime coupling chemistry at physiological pH.

PubMed

Wang, Shujiang; Gurav, Deepanjali; Oommen, Oommen P; Varghese, Oommen P

2015-04-07

The dynamic covalent-coupling reaction involving α-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of α-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a ∼14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Micellar catalyzed degradation of fenitrothion, an organophosphorus pesticide, in solution and soils.

PubMed

Balakrishnan, Vimal K; Buncel, Erwin; Vanloon, Gary W

2005-08-01

We report on a study of the decomposition of fenitrothion (an organophosphorus pesticide that is a persistent contaminant in soils and groundwater) as catalyzed by cetyltrimethylammonium (CTA+) micelles. The CTA micelles were associated with two types of counterions: (1) inert counterions (e.g. CTABr) and (2) reactive counterions (e.g. CTAOH). The reactive counterion surfactants used were hydroxide anion (HO-) as a normal nucleophile and hydroperoxide anion (HOO-) and the anion of pyruvaldehyde oxime (MINA-) as two alpha-nucleophiles. The reactivity order followed: CTABr < CTAOH < CTAMINA < CTAOOH. Treatment of the rate data using the Pseudo-Phase Ion Exchange (PPIE) model of micellar catalysis showed the ratio k2M/k2w to be less than unity for all the surfactants employed. Rather than arising from a "true catalysis", we attributed the observed rate enhancements to a "concentration effect", where both pesticide and nucleophile were incorporated into the small micellar phase volume. Furthermore, the CTAOOH/CTAOH pair gave an alpha-effect of 57, showing that the alpha-effect can play an important role in micellar systems. We further investigated the effectiveness of reactive counterion surfactants in decontaminating selected environmental solids that were spiked with 27 ppb fenitrothion. The solids were as follows: the clay mineral montmorillonite and SO-1 and S0-2 soils (obtained from the Canadian Certified Reference Materials Project). The reactive counterion surfactant solutions significantly enhanced the rate of fenitrothion degradation in the spiked solids over that obtained when the spiked solid was placed in contact with either 0.02 M KOH or water. The rate enhancements followed the order CTAOOH > CTAMINA approximately CTAOH > KOH > water. We conclude that reactive counterion surfactants, especially with alpha-nucleophiles, hold great potential in terms of remediating soils contaminated by toxic organophosphorus esters.

Gallium-containing polymer brush film as efficient supported Lewis acid catalyst in a glass microreactor.

PubMed

Munirathinam, Rajesh; Ricciardi, Roberto; Egberink, Richard J M; Huskens, Jurriaan; Holtkamp, Michael; Wormeester, Herbert; Karst, Uwe; Verboom, Willem

2013-01-01

Polystyrene sulfonate polymer brushes, grown on the interior of the microchannels in a microreactor, have been used for the anchoring of gallium as a Lewis acid catalyst. Initially, gallium-containing polymer brushes were grown on a flat silicon oxide surface and were characterized by FTIR, ellipsometry, and X-ray photoelectron spectroscopy (XPS). XPS revealed the presence of one gallium per 2-3 styrene sulfonate groups of the polymer brushes. The catalytic activity of the Lewis acid-functionalized brushes in a microreactor was demonstrated for the dehydration of oximes, using cinnamaldehyde oxime as a model substrate, and for the formation of oxazoles by ring closure of ortho-hydroxy oximes. The catalytic activity of the microreactor could be maintained by periodic reactivation by treatment with GaCl3.

Reactivation of VX-inhibited cholinesterase by 2-PAM and HS-6 in rats.

PubMed

Harris, L W; Stitcher, D L

1983-01-01

Atropinized rats intoxicated with ethyl-S-2-diisopropyl aminoethyl methyl phosphonothioate (VX), 15 mg/kg iv, were divided into three groups and were treated with normal saline, iv, 30 mg/kg of 2-PAM C1, iv, and 30 mg/kg of HS-6, iv. One hr after administration of therapy they were decapitated and cholinesterase (ChE) activity was determined on blood, brain and diaphragm tissue. Both 2-PAM C1 and HS-6 markedly reactivated VX-inhibited blood and diaphragm ChE. Brain ChE activity was not significantly reactivated by either oxime. The effectiveness of these oximes in restoration of VX-inactivated ChE in vivo offers an explanation as to why conventional atropine/oxime therapy is so effective against VX intoxication.

Catalytic Nucleophilic Glyoxylation of Aldehydes

PubMed Central

Steward, Kimberly M.; Johnson, Jeffrey S.

2010-01-01

β-Silyloxy-α-ketoesters are prepared through a cyanide-catalyzed benzoin-type reaction with silyl glyoxylates and aldehydes. The products undergo a dynamic kinetic resolution to provide enantioenriched orthogonally protected alcohols and can be converted to the corresponding β-silyloxy-α-aminoesters. PMID:20481613

Bisquaternary pyridinium oximes: Comparison of in-vitro reactivation potency of compounds bearing aliphatic linkers and heteroaromatic linkers for paraoxon-inhibited electric eel and recombinant human acetylcholinesterase

PubMed Central

Bharate, Sandip B.; Guo, Lilu; Reeves, Tony E.; Cerasoli, Douglas M.; Thompson, Charles M.

2009-01-01

Oxime reactivators are the drugs of choice for the post-treatment of OP (organophosphorus) intoxication and used widely for mechanistic and kinetic studies of OP-inhibited cholinesterases. The purpose of the present study was to evaluate new oxime compounds to reactivate acetylcholinesterase (AChE) inhibited by the OP paraoxon. Several new bisquaternary pyridinium oximes with heterocyclic linkers along with some known bisquaternary pyridinium oximes bearing aliphatic linkers were synthesized and evaluated for their in vitro reactivation potency against paraoxon-inhibited electric eel acetylcholinesterase (EeAChE) and recombinant human acetylcholinesterase (rHuAChE). Results herein indicate that most of the compounds are better reactivators of EeAChE than of rHuAChE. The reactivation potency of two different classes of compounds with varying linker chains was compared and observed that the structure of the connecting chain is an important factor for the activity of the reactivators. At a higher concentration (10−3 M), compounds bearing aliphatic linker showed better reactivation than compounds with heterocyclic linkers. Interestingly, oximes with a heterocyclic linker inhibited AChE at higher concentration (10−3 M), whereas their ability to reactivate was increased at lower concentrations (10−4 M and 10−5 M). Compounds bearing either a thiophene linker 26, 46 or a furan linker 31 showed 59%, 49% and 52% reactivation of EeAChE, respectively, at 10−5 M. These compounds showed 14%, 6% and 15% reactivation of rHuAChE at 10−4 M. Amongst newly synthesized analogs with heterocyclic linkers (26–35 and 45–46), compound 31, bearing furan linker chain, was found to be the most effective reactivator with a kr 0.042 min−1, which is better than obidoxime (3) for paraoxon-inhibited EeAChE. Compound 31 showed a kr 0.0041 min−1 that is near equal to pralidoxime (1) for paraoxon-inhibited rHuAChE. PMID:20005727

Gallium-containing polymer brush film as efficient supported Lewis acid catalyst in a glass microreactor

PubMed Central

Munirathinam, Rajesh; Ricciardi, Roberto; Egberink, Richard J M; Huskens, Jurriaan; Holtkamp, Michael; Wormeester, Herbert; Karst, Uwe

2013-01-01

Summary Polystyrene sulfonate polymer brushes, grown on the interior of the microchannels in a microreactor, have been used for the anchoring of gallium as a Lewis acid catalyst. Initially, gallium-containing polymer brushes were grown on a flat silicon oxide surface and were characterized by FTIR, ellipsometry, and X-ray photoelectron spectroscopy (XPS). XPS revealed the presence of one gallium per 2–3 styrene sulfonate groups of the polymer brushes. The catalytic activity of the Lewis acid-functionalized brushes in a microreactor was demonstrated for the dehydration of oximes, using cinnamaldehyde oxime as a model substrate, and for the formation of oxazoles by ring closure of ortho-hydroxy oximes. The catalytic activity of the microreactor could be maintained by periodic reactivation by treatment with GaCl3. PMID:24062830

Oxime ether lipids containing hydroxylated head groups are more superior siRNA delivery agents than their nonhydroxylated counterparts.

PubMed

Gupta, Kshitij; Mattingly, Stephanie J; Knipp, Ralph J; Afonin, Kirill A; Viard, Mathias; Bergman, Joseph T; Stepler, Marissa; Nantz, Michael H; Puri, Anu; Shapiro, Bruce A

2015-01-01

To evaluate the structure-activity relationship of oxime ether lipids (OELs) containing modifications in the hydrophobic domains (chain length, degree of unsaturation) and hydrophilic head groups (polar domain hydroxyl groups) toward complex formation with siRNA molecules and siRNA delivery efficiency of resulting complexes to a human breast cancer cell line (MDA-MB-231). Ability of lipoplex formation between oxime ether lipids with nucleic acids were examined using biophysical techniques. The potential of OELs to deliver nucleic acids and silence green fluorescent protein (GFP) gene was analyzed using MDA-MB-231 and MDA-MB-231/GFP cells, respectively. Introduction of hydroxyl groups to the polar domain of the OELs and unsaturation into the hydrophobic domain favor higher transfection and gene silencing in a cell culture system.

Configurational and conformational preferences in oximes and oxime carbanions. Ab initio study of the syn effect in reactions of oxyimine enolate equivalents

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

Glaser, R.; Streitwieser, A.

1989-09-13

Geometries and relative energies of stationary structures of several conformers of geometrical isomers of NO s-trans-configured acetaldoxime are reported. The calculated energies and geometries agree well with comparable experimental data. Effects of the theoretical model on the NO band lengths are discussed for formaldoxime. The theoretical results suggest that the regiochemistry of enolate equivalents of oxyimines in dissociating solvents is due to the thermodynamic syn preference of the anions. Syn/anti isomerization of the anions (E{sub a} < 26 kcal mol{sup {minus}1}) is rapid even at low temperatures. In contrast, the anti preference of the radicals of acetaldoxime indicates that themore » formation of the syn products in oxidative coupling reactions of the anions of oxime ethers is a kinetic effect.« less

Multiple QSAR models, pharmacophore pattern and molecular docking analysis for anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues

NASA Astrophysics Data System (ADS)

Masand, Vijay H.; El-Sayed, Nahed N. E.; Bambole, Mukesh U.; Quazi, Syed A.

2018-04-01

Multiple discrete quantitative structure-activity relationships (QSARs) models were constructed for the anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues with a variety of substituents like sbnd Br, sbnd OH, -OMe, etc. at different positions. A big pool of descriptors was considered for QSAR model building. Genetic algorithm (GA), available in QSARINS-Chem, was executed to choose optimum number and set of descriptors to create the multi-linear regression equations for a dataset of sixty-nine compounds. The newly developed five parametric models were subjected to exhaustive internal and external validation along with Y-scrambling using QSARINS-Chem, according to the OECD principles for QSAR model validation. The models were built using easily interpretable descriptors and accepted after confirming statistically robustness with high external predictive ability. The five parametric models were found to have R2 = 0.80 to 0.86, R2ex = 0.75 to 0.84, and CCCex = 0.85 to 0.90. The models indicate that frequency of nitrogen and oxygen atoms separated by five bonds from each other and internal electronic environment of the molecule have correlation with the anticancer activity.

Role of dbnd NOH intermolecular interactions in oxime derivatives via Crystal structure, Hirshfeld surface, PIXELC and DFT calculations

NASA Astrophysics Data System (ADS)

Purushothaman, Gayathri; Thiruvenkatam, Vijay

2017-11-01

Oximes are building block of organic synthesis and they have wide range applications in laboratories, industries, and pharmaceutical as antidotes. Herein we report the crystal structures of oxime derivative Beta-p-Dimethylaminodeoxybenzionoxime (I) and o-Chloro-p-dimethylaminodeoxybenzion (II) the precursor molecule of o-Chloro-p-dimethylaminodeoxybenzionoxime and their intermolecular interactions studies through Hirshfeld surface & 2D-fingerprint plot analysis along with PIXELC and DFT calculations. The packing arrangements in I and II are driven by Osbnd H⋯N and Osbnd H⋯C interactions respectively. The Osbnd H⋯N hydrogen bonding in I facilitates the formation of the dimer with the motif of R (22(6)), whereas in II absence of oxime moiety (dbnd NOH) restricts the dimer formation. The 2D-fingerprint plot shows the close contacts for the intermolecular interactions in I & II. The PIXELC calculation of II suggests Osbnd H⋯C contributes for intermolecular interaction that stabilizes the crystal packing with the total energy value of 60.4 kcal/mol. The DFT calculation using B3LYP with 6-311G (d, p) functional set for both the derivatives shows a small deviation in the benzene ring (I) and chlorobenzene ring (II) with the RMSD value of 0.5095 Å and 0.8472 Å respectively.

Comparative reactivity of different types of stable cyclic and acyclic mono- and diamino carbenes with simple organic substrates.

PubMed

Martin, David; Canac, Yves; Lavallo, Vincent; Bertrand, Guy

2014-04-02

A series of stable carbenes, featuring a broad range of electronic properties, were reacted with simple organic substrates. The N,N-dimesityl imidazolylidene (NHC) does not react with isocyanides, whereas anti-Bredt di(amino)carbene (pyr-NHC), cyclic (alkyl)(amino)carbene (CAAC), acyclic di(amino)carbene (ADAC), and acyclic (alkyl)(amino)carbene (AAAC) give rise to the corresponding ketenimines. NHCs are known to promote the benzoin condensation, and we found that the CAAC, pyr-NHC, and ADAC react with benzaldehyde to give the ketone tautomer of the Breslow intermediate, whereas the AAAC first gives the corresponding epoxide and ultimately the Breslow intermediate, which can be isolated. Addition of excess benzaldehyde to the latter does not lead to benzoin but to a stable 1,3-dioxolane. Depending on the electronic properties of carbenes, different products are also obtained with methyl acrylate as a substrate. The critical role of the carbene electrophilicity on the outcome of reactions is discussed.

Spectrofluorimetric analysis of famotidine in pharmaceutical preparations and biological fluids by derivatization with benzoin.

PubMed

Alamgir, Malik; Khuhawar, Muhammad Yar; Memon, Saima Q; Hayat, Amir; Zounr, Rizwan Ali

2015-01-05

A sensitive and simple spectrofluorimetric method has been developed for the analysis of famotidine, from pharmaceutical preparations and biological fluids after derivatization with benzoin. The reaction was carried out in alkaline medium with measurement of fluorescence intensity at 446 nm with excitation wavelength at 286 nm. Linear calibration was obtained with 0.5-15 μg/ml with coefficient of determination (r(2)) 0.997. The factors affecting the fluorescence intensity were optimized. The pharmaceutical additives and amino acid did not interfere in the determination. The mean percentage recovery (n=4) calculated by standard addition from pharmaceutical preparation was 94.8-98.2% with relative standard deviation (RSD) 1.56-3.34% and recovery from deproteinized spiked serum and urine of healthy volunteers was 98.6-98.9% and 98.0-98.4% with RSD 0.34-0.84% and 0.29-0.87% respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Basic medium oxidation of aromatic α-hydroxy-ketones: A free radical mechanism

NASA Astrophysics Data System (ADS)

Gómez-Vidales, Virginia; Vargas, Marina; Meléndez, Iván; Salmón, Manuel; Sansón-O, Carmen; Zaragoza, I. P.; Zolotukhin, Mikhail; Salcedo, Roberto

2010-01-01

A systematic study was undertaken of the EPR of sodium hydroxide solutions of Benzoin, Anisoin and Thenoin in both ethanol and DMSO as well as their corresponding ionised species of varying colours. In all cases, the EPR consist of symmetric spectra, resulting from the generation of a free radical-anion. Furthermore, theoretical DFT methods were applied in order to study the radical anions, revealing the reason for the colour change in the solutions and in the case of benzoin, found to be related to the interaction between the cis and trans-isomers with the molecules in the two solvents. We have defined the structure of the cis-isomer and for the first time we have described how the adduct between the cis-isomer and the solvent molecule, results in a stable conformer. This corresponds with the EPR results which indicated a significant difference between the cis and trans-isomers. Both the theoretical and experimental results inspired similar descriptions of the significant differences between the cis and trans-isomers in solution.

High efficiency labeling of glycoproteins on living cells

PubMed Central

Zeng, Ying; Ramya, T. N. C.; Dirksen, Anouk; Dawson, Philip E.; Paulson, James C.

2010-01-01

We describe a simple method for efficiently labeling cell surface glycans on virtually any living animal cell. The method employs mild Periodate oxidation to generate an aldehyde on sialic acids, followed by Aniline-catalyzed oxime Ligation with a suitable tag (PAL). Aniline catalysis dramatically accelerates oxime ligation, allowing use of low concentrations of aminooxy-biotin at neutral pH to label the majority of cell surface glycoproteins while maintaining high cell viability. PMID:19234450

Central Acetylcholinesterase Reactivation by Oximes Improves Survival and Terminates Seizures Following Nerve Agent Intoxication

DTIC Science & Technology

2009-01-01

activity ; GB = sarin; im = intramuscular; ip = intraperitoneal; LD50 = median lethal dose 50%; MINA = monoisonitrosoacetone; MMB-4 = methoxime; OP...inhibited acetylcholinesterase (AChE) activity . We have studied the capability of the tertiary oximes monoisonitrosoacetone (MINA) and diacetylmonoxime...of 20, 26, 35, 46 and 60 mg/kg, there were 0, 9, 17, 60, and 75%, respectively, of animals never exhibited EEG seizure activity with 43, 64, 75, 90

Theoretical and experimental studies of 3β-acetoxy-5α-cholestan-6-one oxime

NASA Astrophysics Data System (ADS)

Khan, Azhar U.; Avecillia, Fernando; Malik, Nazia; Khan, Md. Shahzad; Khan, Mohd Shahid; Mushtaque, Md.

2016-10-01

Steroidal oxime (3β-acetoxy-5α-cholestan- 6-one oxime) has been synthesized using microwave-induced reaction in 3.5 min using saturated steroidal ketone and aqueous hydroxylamine hydrochloride in ethanol. The structure of the compound was elucidated by UV, IR, 1H NMR and X-ray single crystal structure. The computational quantum chemical studies like, IR, UV analysis were performed by density functional theory (DFT) at Becke-3-Lee-Yang-Parr(B3LYP) exchange-correlation functional in combination with 6-31++G(d,p) basis sets. The harmonic vibrational frequencies, the optimized geometric parameters have been interpreted and compared with experimental values. Theoretical wavelength at 214.88 cm-1 correspond to the experimental value 214.0 cm-1. The nature of this transition is n → π*. The theoretical results are in good agreement with experiment results.

Different approaches to acute organophosphorus poison treatment.

PubMed

Nurulain, Syed Muhammad

2012-07-01

Organophosphorus compounds (OPCs) have a wide variety of applications and are a serious threat for self-poisoning, unintentional misuse, terrorist attack, occupational hazard and warfare attack. The present standard treatment has been reported to be unsatisfactory. Many novel approaches are being used and tested for acute organophosphorus (OP) poison treatment. The bioscavenger concept captured high attention among the scientific community during the last few decades. Other approaches like alkalinisation of blood plasma/serum and use of weak inhibitors against strong inhibitors, though it showed promising results, did not get such wide attention. The introduction of a novel broad-spectrum oxime has also been in focus. In this mini-review, an update of the overview of four different approaches has been discussed. The standard therapy that is atropine+oxime+benzodiazepine along with supportive measures will continue to be the best option with only the replacement of a single oxime to improve its broad-spectrum efficacy.

The HSP90 binding mode of a radicicol-like E-oxime from docking, binding free energy estimations, and NMR 15N chemical shifts

PubMed Central

Spichty, Martin; Taly, Antoine; Hagn, Franz; Kessler, Horst; Barluenga, Sofia; Winssinger, Nicolas; Karplus, Martin

2009-01-01

We determine the binding mode of a macrocyclic radicicol-like oxime to yeast HSP90 by combining computer simulations and experimental measurements. We sample the macrocyclic scaffold of the unbound ligand by parallel tempering simulations and dock the most populated conformations to yeast HSP90. Docking poses are then evaluated by the use of binding free energy estimations with the linear interaction energy method. Comparison of QM/MM-calculated NMR chemical shifts with experimental shift data for a selective subset of back-bone 15N provides an additional evaluation criteria. As a last test we check the binding modes against available structure-activity-relationships. We find that the most likely binding mode of the oxime to yeast HSP90 is very similar to the known structure of the radicicol-HSP90 complex. PMID:19482409

Oxime ether lipids containing hydroxylated head groups are more superior siRNA delivery agents than their nonhydroxylated counterparts

PubMed Central

Gupta, Kshitij; Mattingly, Stephanie J; Knipp, Ralph J; Afonin, Kirill A; Viard, Mathias; Bergman, Joseph T; Stepler, Marissa; Nantz, Michael H; Puri, Anu; Shapiro, Bruce A

2015-01-01

Aim: To evaluate the structure–activity relationship of oxime ether lipids (OELs) containing modifications in the hydrophobic domains (chain length, degree of unsaturation) and hydrophilic head groups (polar domain hydroxyl groups) toward complex formation with siRNA molecules and siRNA delivery efficiency of resulting complexes to a human breast cancer cell line (MDA-MB-231). Materials & methods: Ability of lipoplex formation between oxime ether lipids with nucleic acids were examined using biophysical techniques. The potential of OELs to deliver nucleic acids and silence green fluorescent protein (GFP) gene was analyzed using MDA-MB-231 and MDA-MB-231/GFP cells, respectively. Results & conclusion: Introduction of hydroxyl groups to the polar domain of the OELs and unsaturation into the hydrophobic domain favor higher transfection and gene silencing in a cell culture system. PMID:26107486

New Organocatalyst Scaffolds with High Activity in Promoting Hydrazone and Oxime Formation at Neutral pH

PubMed Central

2015-01-01

The discovery of two new classes of catalysts for hydrazone and oxime formation in water at neutral pH, namely 2-aminophenols and 2-(aminomethyl)benzimidazoles, is reported. Kinetics studies in aqueous solutions at pH 7.4 revealed rate enhancements up to 7-fold greater than with classic aniline catalysis. 2-(Aminomethyl)benzimidazoles were found to be effective catalysts with otherwise challenging aryl ketone substrates. PMID:25545888

Design and Synthesis of Bifunctional Oxime Reactivators of OP- inhibited Cholinesterase

DTIC Science & Technology

2013-08-01

was introduce the 2- aldehyde as a nitrile via the pyridine N-oxide. Another approach (II), was to simply perform 2- hydoxymethylation of pyridines...original design plan called for introducing an aldehyde that could be coupled to various amines and diamines through reductive amination. Interestingly...chromatography DCM: MeOH (90:10) as a yellow oil. Synthesis of 37 (Oxime formation general procedure) To the ketone 36 (340 mg, 1,123 mmol) in 1

In vitro ability of currently available oximes to reactivate organophosphate pesticide-inhibited human acetylcholinesterase and butyrylcholinesterase.

PubMed

Jun, Daniel; Musilova, Lucie; Musilek, Kamil; Kuca, Kamil

2011-01-01

We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to reactivate human acetylcholinesterase (AChE), inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos). We also tested reactivation of human butyrylcholinesterase (BChE) with the aim of finding a potent oxime, suitable to serve as a "pseudocatalytic" bioscavenger in combination with this enzyme. Such a combination could allow an increase of prophylactic and therapeutic efficacy of the administered enzyme. According to our results, the best broad-spectrum AChE reactivators were trimedoxime and obidoxime in the case of paraoxon, leptophos-oxon, and methamidophos-inhibited AChE. Methamidophos and leptophos-oxon were quite easily reactivatable by all tested reactivators. In the case of methamidophos-inhibited AChE, the lower oxime concentration (10(-5) M) had higher reactivation ability than the 10(-4) M concentration. Therefore, we evaluated the reactivation ability of obidoxime in a concentration range of 10(-3)-10(-7) M. The reactivation of methamidophos-inhibited AChE with different obidoxime concentrations resulted in a bell shaped curve with maximum reactivation at 10(-5) M. In the case of BChE, no reactivator exceeded 15% reactivation ability and therefore none of the oximes can be recommended as a candidate for "pseudocatalytic" bioscavengers with BChE.

Aminooxylated Carbohydrates: Synthesis and Applications.

PubMed

Pifferi, Carlo; Daskhan, Gour Chand; Fiore, Michele; Shiao, Tze Chieh; Roy, René; Renaudet, Olivier

2017-08-09

Among other classes of biomolecules, carbohydrates and glycoconjugates are widely involved in numerous biological functions. In addition to addressing the related synthetic challenges, glycochemists have invested intense efforts in providing access to structures that can be used to study, activate, or inhibit these biological processes. Over the past few decades, aminooxylated carbohydrates have been found to be key building blocks for achieving these goals. This review provides the first in-depth overview covering several aspects related to the syntheses and applications of aminooxylated carbohydrates. After a brief introduction to oxime bonds and their relative stabilities compared to related C═N functions, synthetic aspects of oxime ligation and methodologies for introducing the aminooxy functionality onto both glycofuranosyls and glycopyranosyls are described. The subsequent section focuses on biological applications involving aminooxylated carbohydrates as components for the construcion of diverse architectures. Mimetics of natural structures represent useful tools for better understanding the features that drive carbohydrate-receptor interaction, their biological output and they also represent interesting structures with improved stability and tunable properties. In the next section, multivalent structures such as glycoclusters and glycodendrimers obtained through oxime ligation are described in terms of synthetic design and their biological applications such as immunomodulators. The second-to-last section discusses miscellaneous applications of oxime-based glycoconjugates, such as enantioselective catalysis and glycosylated oligonucleotides, and conclusions and perspectives are provided in the last section.

Detoxification of tabun at physiological pH mediated by substituted β-cyclodextrin and glucose derivatives containing oxime groups.

PubMed

Brandhuber, Florian; Zengerle, Michael; Porwol, Luzian; Tenberken, Oliver; Thiermann, Horst; Worek, Franz; Kubik, Stefan; Reiter, Georg

2012-12-16

The ability of 13 β-cyclodextrin and 2 glucose derivatives containing substituents with oxime groups as nucleophilic components to accelerate the degradation of tabun at physiological pH has been evaluated. To this end, a qualitative and a quantitative enzymatic assay as well as a highly sensitive enantioselective GC-MS assay were used. In addition, an assay was developed that provided information about the mode of action of the investigated compounds. The results show that attachment of pyridinium-derived substituents with an aldoxime group in 3- or 4-position to a β-cyclodextrin ring affords active compounds mediating tabun degradation. Activities differ depending on the structure, the number, and the position of the substituent on the ring. Highest activity was observed for a β-cyclodextrin containing a 4-formylpyridinium oxime residue in 6-position of one glucose subunit, which detoxifies tabun with a half-time of 10.2 min. Comparison of the activity of this compound with that of an analog in which the cyclodextrin ring was replaced by a glucose residue demonstrated that the cyclodextrin is not necessary for activity but certainly beneficial. Finally, the results provide evidence that the mode of action of the cyclodextrin involves covalent modification of its oxime group rendering the scavenger inactive after reaction with the first tabun molecule. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

FTIR study of the photoreaction of bovine rhodopsin in the presence of hydroxylamine.

PubMed

Katayama, Kota; Furutani, Yuji; Kandori, Hideki

2010-07-15

In bovine rhodopsin, 11-cis-retinal forms a Schiff base linkage with Lys296. The Schiff base is not reactive to hydroxylamine in the dark, which is consistent with the well-protected retinal binding site. In contrast, under illumination it easily forms all-trans retinal oxime, resulting in the loss of color. This suggests that activation of rhodopsin creates a specific reaction channel for hydroxylamine or loosens the chromophore binding pocket. In the present study, to extract structural information on the Schiff base vicinity and to understand the changes upon activation of rhodopsin, we compared light-induced FTIR difference spectra of bovine rhodopsin in the presence and absence of hydroxylamine under physiological pH (approximately 7). Although the previous FTIR study did not observe the complex formation between rhodopsin and G-protein transducin in hydrated films, the present study clearly shows that hydrated films can be used for studies of the interaction between rhodopsin and hydroxylamine. Hydroxylamine does not react with the Schiff base of Meta-I intermediate trapped at 240 K, possibly because of decreased conformational motions under the frozen environment, while FTIR spectroscopy showed that hydroxylamine affects the hydrogen bonds of the Schiff base and water molecules in Meta-I. In contrast, formation of the retinal oxime was clearly observed at 280 K, the characteristic temperature of Meta-II accumulation in the absence of hydroxylamine, and time-dependent formation of retinal oxime was observed from Meta-II at 265 K as well. The obtained difference FTIR spectra of retinal oxime and opsin are different from that of Meta-II. It is likely that the antiparallel beta-sheet constituting a part of the retinal binding pocket at the extracellular surface is structurally disrupted in the presence of hydroxylamine, which allows the hydrolysis of the Schiff base into retinal oxime.

Observation and explanation of two-dimensional interconversion of oximes with multiple heart-cutting using comprehensive multidimensional gas chromatography.

PubMed

Kulsing, Chadin; Nolvachai, Yada; Wong, Yong Foo; Glouzman, Melissa I; Marriott, Philip J

2018-04-20

Real-time interconversion processes produce unconventional peak broadening in gas chromatography (GC), and can be used to generate kinetic and thermodynamic data. In this study, an unusual separation situation in comprehensive two dimensional GC where two dimensional interconversion (i.e. a raised plateau in both first and second dimension, 1 D and 2 D) was observed in analysis of oxime isomers. This resulted in a characteristic and unusual rectangular peak shape in the two dimensional result. A related theoretical approach was introduced to explain the peak shape supported by simulation results which can be varied depending on concentration profiles and kinetics of the process. The simulated results were supported by experimental results obtained by a comprehensive heart-cut multidimensional GC (H/C MDGC) approach which was developed to clearly investigate isomerisation of E/Z oxime molecules in both 1 D and 2 D separations under different isothermal conditions. The carrier gas flow and oven temperature were selected according to initial results for 1D interconversion on a poly(ethyleneglycol) stationary phase, which was further used in both 1 D and 2 D separations to result in broad zones of oxime interconversion in both dimensions. The method involved repetitive injections of oxime sample, then sampling contiguous fractions of sample into a long 2 D column which is intended to promote considerable interconversion. Comprehensiveness arises from the fact that the whole sample is sampled from the 1 D to the 2 D column, with the long 2 D column replacing the short 2 D column used in classical comprehensive two-dimensional gas chromatography, where the latter will not promote sufficient interconversion. Data processing and presentation permits a 'rectangular' distribution corresponding to the separated compounds, characteristic of this experiment. Copyright © 2018 Elsevier B.V. All rights reserved.

Rh(III)-Catalyzed Decarboxylative Coupling of Acrylic Acids with Unsaturated Oxime Esters: Carboxylic Acids Serve as Traceless Activators

PubMed Central

2015-01-01

α,β-Unsaturated carboxylic acids undergo Rh(III)-catalyzed decarboxylative coupling with α,β-unsaturated O-pivaloyl oximes to provide substituted pyridines in good yield. The carboxylic acid, which is removed by decarboxylation, serves as a traceless activating group, giving 5-substituted pyridines with very high levels of regioselectivity. Mechanistic studies rule out a picolinic acid intermediate, and an isolable rhodium complex sheds further light on the reaction mechanism. PMID:24512241

Application of oxime-diversification to optimize ligand interactions within a cryptic pocket of the polo-like kinase 1 polo-box domain | Center for Cancer Research

Cancer.gov

By a process involving initial screening of a set of 87 aldehydes using an oxime ligation-based strategy, we were able to achieve a several-fold affinity enhancement over one of the most potent previously known polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors. This improved binding may result by accessing a newly identified auxiliary region proximal to a key

Construction of New Potential Reactivators of Phosphonylated Acetylcholinesterase. Substitution of F for H in the Nucleus of Pyridinecarboxaldehyde Oximes.

DTIC Science & Technology

1983-11-01

essential to the content of the re- port and in all cases NMR data subjected to interpretation in this report have been entered in typography to...compared. In the Second Quarter reactions in the synthetic pathway to 3-F-2-PAM were scaled-up. Low yields were encountered for the specific nitration...oxime was synthetically achieved by way of the Markovac-Stevens-Ash-Hackley reaction , and the compound was characterized by its mass spectrum, NMR

Perspectives on the Use of Scopolamine as an Adjunct Treatment to Enhance Survival Following Organophosphorus Nerve Agent Poisoning

DTIC Science & Technology

2010-11-01

particular nerve agent and oxime uti- lized in the treatment regimen. Atropine is the universal treatment for organophospho- rus anticholinesterase poisoning...general, to the recovery of AChE activity either through decarbamylation of PB protected enzyme or by use of an effective oxime. The results against...this protected enzyme in the first few minutes after intoxication and treat- ment provides sufficient enzyme activity to sustain survival.̂ ’"* A

Detection of homing-in of stem cells labeled with technetium-99m hexamethylpropyleneamine oxime in infarcted myocardium after intracoronary injection

PubMed Central

Patel, Chetan D; Agarwal, Snehlata; Seth, Sandeep; Mohanty, Sujata; Aggarwal, Himesh; Gupta, Namit

2014-01-01

Bone marrow stem cells having myogenic potential are promising candidates for various cell-based therapies for myocardial disease. We present here images showing homing of technetium-99m (Tc-99m) hexamethylpropyleneamine oxime (HMPAO) labeled stem cells in the infarcted myocardium from a pilot study conducted to radio-label part of the stem cells in patients enrolled in a stem cell clinical trial for recent myocardial infarction. PMID:25400375

The AB Initio Mia Method: Theoretical Development and Practical Applications

NASA Astrophysics Data System (ADS)

Peeters, Anik

The bottleneck in conventional ab initio Hartree -Fock calculations is the storage of the electron repulsion integrals because their number increases with the fourth power of the number of basis functions. This problem can be solved by a combination of the multiplicative integral approximation (MIA) and the direct SCF method. The MIA approach was successfully applied in the geometry optimisation of some biologically interesting compounds like the neurolepticum Haloperidol and two TIBO derivatives, inactivators of HIV1. In this thesis the potency of the MIA-method is shown by the application of this method in the calculation of the forces on the nuclei. In addition, the MIA method enabled the development of a new model for performing crystal field studies: the supermolecule model. The results for this model are in better agreement with experimental data than the results for the point charge model. This is illustrated by the study of some small molecules in the solid state: 2,3-diketopiperazine, formamide oxime and two polymorphic forms of glycine, alpha-glycine and beta-glycine.

Determination of Carbonyl Functional Groups in Bio-oils by Potentiometric Titration: The Faix Method.

PubMed

Black, Stuart; Ferrell, Jack R

2017-02-07

Carbonyl compounds present in bio-oils are known to be responsible for bio-oil property changes upon storage and during upgrading. Specifically, carbonyls cause an increase in viscosity (often referred to as 'aging') during storage of bio-oils. As such, carbonyl content has previously been used as a method of tracking bio-oil aging and condensation reactions with less variability than viscosity measurements. Additionally, carbonyls are also responsible for coke formation in bio-oil upgrading processes. Given the importance of carbonyls in bio-oils, accurate analytical methods for their quantification are very important for the bio-oil community. Potentiometric titration methods based on carbonyl oximation have long been used for the determination of carbonyl content in pyrolysis bio-oils. Here, we present a modification of the traditional carbonyl oximation procedures that results in less reaction time, smaller sample size, higher precision, and more accurate carbonyl determinations. While traditional carbonyl oximation methods occur at room temperature, the Faix method presented here occurs at an elevated temperature of 80 °C.

Fe-polyaniline composite nanofiber catalyst for chemoselective hydrolysis of oxime.

PubMed

Mahato, Sanjit Kumar; Bhaumik, Madhumita; Maji, Arun; Dutta, Abhijit; Maiti, Debabrata; Maity, Arjun

2018-03-01

A facile chemoselective one-pot strategy for the deprotection of oxime has been developed using Fe 0 -polyaniline composite nanofiber (Fe 0 -PANI), as a catalyst. Nano material based Fe 0 -PANI catalyst has been synthesized via in-situ polymerization of ANI monomer and followed by reductive deposition of Fe 0 onto PANI matrix. The catalyst was characterized by FE-SEM, HR-TEM, BET, XRD, ATR-FTIR, XPS and VSM techniques. The scope of the transformation was studied for aryl, alkyl and heteroarylketoxime with excellent chemoselectivity (>99%). Mechanistic investigations suggested the involvement of a cationic intermediate with Fe 3+ active catalytic species. Substituent effect showed a linear free energy relationship. The activation energy (E a ) was calculated to be 17.46 kJ mol -1 for acetophenone oxime to acetophenone conversion. The recyclability of the catalyst demonstrated up to 10 cycles without any significant loss of efficiency. Based on the preliminary experiments a plausible mechanism has been proposed involving a carbocationic intermediate. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis of 3,5-Isoxazolidinediones and 1H-2,3-Benzoxazine-1,4(3H)-diones from Aliphatic Oximes and Dicarboxylic Acid Chlorides

PubMed Central

2015-01-01

The synthesis of the title compounds was carried out by reacting dicarboxylic acid chlorides with oximes in the presence of excess triethylamine. Disubstituted malonyl chlorides gave 2-alkenyl-4,4-dialkyl-3,5-isoxazolidinediones (8a–f) and 2,2′-ethylidene-bis[4,4-dialkyl-3,5-isoxazolidinedione]s (9a–f). Compounds 9 were formed from 8 and its N-unsubstituted 3,5-isoxazolidinedione decomposition product. Phthaloyl chlorides reacted with acetone oxime to yield 3-(1-methylethenyl)-1H-2,3-benzoxazine-1,4(3H)-diones (16a–e). Products 16 spontaneously decomposed to give N-unsubstituted 1H-2,3-benzoxazine-1,4(3H)-diones (17a–e) at rates that were dependent on temperature and solvent. Kinetic studies showed that two of the compounds decomposed by zero-order kinetics under neutral conditions. Butanedioyl chloride did not produce a cyclic product. PMID:24620711

Synthesis of 3,5-isoxazolidinediones and 1H-2,3-benzoxazine-1,4(3H)-diones from aliphatic oximes and dicarboxylic acid chlorides.

PubMed

Izydore, Robert A; Jones, Joseph T; Mogesa, Benjamin; Swain, Ira N; Davis-Ward, Ronda G; Daniels, Dwayne L; Kpakima, Felicia Frazier; Spaulding-Phifer, Sharnelle T

2014-04-04

The synthesis of the title compounds was carried out by reacting dicarboxylic acid chlorides with oximes in the presence of excess triethylamine. Disubstituted malonyl chlorides gave 2-alkenyl-4,4-dialkyl-3,5-isoxazolidinediones (8a-f) and 2,2'-ethylidene-bis[4,4-dialkyl-3,5-isoxazolidinedione]s (9a-f). Compounds 9 were formed from 8 and its N-unsubstituted 3,5-isoxazolidinedione decomposition product. Phthaloyl chlorides reacted with acetone oxime to yield 3-(1-methylethenyl)-1H-2,3-benzoxazine-1,4(3H)-diones (16a-e). Products 16 spontaneously decomposed to give N-unsubstituted 1H-2,3-benzoxazine-1,4(3H)-diones (17a-e) at rates that were dependent on temperature and solvent. Kinetic studies showed that two of the compounds decomposed by zero-order kinetics under neutral conditions. Butanedioyl chloride did not produce a cyclic product.

DFT conformational studies of the HI-6 molecule

NASA Astrophysics Data System (ADS)

Silva, Gustavo R.; Borges, Itamar; Figueroa-Villar, Jose D.

A systematic study of the oxime HI-6 [1-(2-hydroxyiminomethyl-1-pyridinium)-1-(4-carboxy-aminopyridinium)dimethyl ether] hydrochloride, which is one of the most promising antidotes against soman intoxication, was carried out using density functional theory with the B3LYP (Becke, Lee, Yang, and Parr) method and the 6-31+G*, 6-31+G*, and 6-31+G** basis sets. Rotational barriers, equilibrium geometries, and charge distributions were calculated in order to investigate the role of the side chain for the larger oximes used as antidotes in the treatment of neurotoxic organophosphate poisoning. Also reported is the comparison between HI-6 and pralidoxime (2-PAM), a smaller oxime previously studied in our research group. It is shown that conformation minima for the protonated E isomer do not depend on the size of the side chain; on the other hand, this effect has a pronounced influence on the protonated Z isomer. For the unprotonated isomers, other effects, such as electrostatic interactions and resonance, should be taken into account in their conformational analysis.

The Catalytic Asymmetric Intramolecular Stetter Reaction

PubMed Central

de Alaniz, Javier Read; Rovis, Tomislav

2010-01-01

This account chronicles our efforts at the development of a catalytic asymmetric Stetter reaction using chiral triazolium salts as small molecule organic catalysts. Advances in the mechanistically related azolium-catalyzed asymmetric benzoin reaction are discussed, particularly as they apply to catalyst design. A chronological treatise of reaction discovery, catalyst optimization and reactivity extension follows. PMID:20585467

Structure of the ThDP-dependent enzyme benzaldehyde lyase refined to 1.65 Å resolution

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

Maraite, Andy; Schmidt, Thomas; Ansörge-Schumacher, Marion B.

2007-07-01

The X-ray crystal structure of the ThDP-dependent enzyme benzaldehyde lyase has been refined to 1.65 Å. Benzaldehyde lyase (BAL; EC 4.1.2.38) is a thiamine diphosphate (ThDP) dependent enzyme that catalyses the enantioselective carboligation of two molecules of benzaldehyde to form (R)-benzoin. BAL has hence aroused interest for its potential in the industrial synthesis of optically active benzoins and derivatives. The structure of BAL was previously solved to a resolution of 2.6 Å using MAD experiments on a selenomethionine derivative [Mosbacher et al. (2005 ▶), FEBS J.272, 6067–6076]. In this communication of parallel studies, BAL was crystallized in an alternative spacemore » group (P2{sub 1}2{sub 1}2{sub 1}) and its structure refined to a resolution of 1.65 Å, allowing detailed observation of the water structure, active-site interactions with ThDP and also the electron density for the co-solvent 2-methyl-2,4-pentanediol (MPD) at hydrophobic patches of the enzyme surface.« less

Extended reaction scope of thiamine diphosphate dependent cyclohexane-1,2-dione hydrolase: from C-C bond cleavage to C-C bond ligation.

PubMed

Loschonsky, Sabrina; Wacker, Tobias; Waltzer, Simon; Giovannini, Pier Paolo; McLeish, Michael J; Andrade, Susana L A; Müller, Michael

2014-12-22

ThDP-dependent cyclohexane-1,2-dione hydrolase (CDH) catalyzes the CC bond cleavage of cyclohexane-1,2-dione to 6-oxohexanoate, and the asymmetric benzoin condensation between benzaldehyde and pyruvate. One of the two reactivities of CDH was selectively knocked down by mutation experiments. CDH-H28A is much less able to catalyze the CC bond formation, while the ability for CC bond cleavage is still intact. The double variant CDH-H28A/N484A shows the opposite behavior and catalyzes the addition of pyruvate to cyclohexane-1,2-dione, resulting in the formation of a tertiary alcohol. Several acyloins of tertiary alcohols are formed with 54-94 % enantiomeric excess. In addition to pyruvate, methyl pyruvate and butane-2,3-dione are alternative donor substrates for CC bond formation. Thus, the very rare aldehyde-ketone cross-benzoin reaction has been solved by design of an enzyme variant. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual-mesoporous ZSM-5 zeolite with highly b-axis-oriented large mesopore channels for the production of benzoin ethyl ether.

PubMed

Zhou, Xiaoxia; Chen, Hangrong; Zhu, Yan; Song, Yudian; Chen, Yu; Wang, Yongxia; Gong, Yun; Zhang, Guobin; Shu, Zhu; Cui, Xiangzhi; Zhao, Jinjin; Shi, Jianlin

2013-07-22

Dual-mesoporous ZSM-5 zeolite with highly b axis oriented large mesopores was synthesized by using nonionic copolymer F127 and cationic surfactant CTAB as co-templates. The product contains two types of mesopores--smaller wormlike ones of 3.3 nm in size and highly oriented larger ones of 30-50 nm in diameter along the b axis--and both of them interpenetrate throughout the zeolite crystals and interconnect with zeolite microporosity. The dual-mesoporous zeolite exhibits excellent catalytic performance in the condensation of benzaldehyde with ethanol and greater than 99 % selectivity for benzoin ethyl ether at room temperature, which can be ascribed to the zeolite lattice structure offering catalytically active sites and the hierarchical and oriented mesoporous structure providing fast access of reactants to these sites in the catalytic reaction. The excellent recyclability and high catalytic stability of the catalyst suggest prospective applications of such unique mesoporous zeolites in the chemical industry. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regio- and Stereoselective Aliphatic-Aromatic Cross-Benzoin Reaction: Enzymatic Divergent Catalysis.

PubMed

Beigi, Maryam; Gauchenova, Ekaterina; Walter, Lydia; Waltzer, Simon; Bonina, Fabrizio; Stillger, Thomas; Rother, Dörte; Pohl, Martina; Müller, Michael

2016-09-19

The catalytic asymmetric synthesis of chiral 2-hydroxy ketones by using different thiamine diphosphate dependent enzymes, namely benzaldehyde lyase from Pseudomonas fluorescens (PfBAL), a variant of benzoylformate decarboxylase from Pseudomonas putida (PpBFD-L461A), branched-chain 2-keto acid decarboxylase from Lactococcus lactis (LlKdcA) and a variant of pyruvate decarboxylase from Acetobacter pasteurianus (ApPDC-E469G), was studied. Starting with the same set of substrates, substituted benzaldehydes in combination with different aliphatic aldehydes, PfBAL and PpBFD-L461A selectively deliver the (R)- and (S)-2-hydroxy-propiophenone derivatives, respectively. The (R)- and (S)-phenylacetylcarbinol (1-hydroxy-1-phenylacetone) derivatives are accessible in a similar way using LlKdcA and ApPDC-E469G, respectively. In many cases excellent stereochemical purities (>98 % enantiomeric excess) could be achieved. Hence, the regio- and stereochemistry of the product in the asymmetric aliphatic-aromatic cross-benzoin reaction can be controlled solely by choice of the appropriate enzyme or enzyme variant. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spectroscopic and pH-metric studies of the complexation of 3-[2-(4-methylquinolin-2-yl)hydrazono]butan-2-one oxime compound.

PubMed

Seleem, H S; El-Inany, G A; Mousa, M; Hanafy, F I

2010-05-01

The electronic absorption spectra of the oximic quinolinyl hydrazone (MHQ; H(2)L) and its Co(II) and Cu(II)-complexes have been studied in Britton-Rhobinson buffer solutions of varying pH's in 75% dioxane-water. The dissociation constant of the hydrazone (pK(H)) as well as the stability constants (logK) of its chelates were determined spectrophotometrically and pH-metrically. The obtained data are in good agreement. Beer's law is valid in the ranges (0.64-6.99) and (2.36-6.48)mug/mL for Cu(II) and Co(II)-ions, respectively. On the other hand, the pK(H) and logK were determined pH-metrically in 75% solvent-water; (solvent=dioxane, ethanol, methanol and isopropanol). The variation of pK(H) or logK as a function of solvent parameters viz. 1/D, E(T), AN and pi* was used to evaluate the dissociation and stability constants in the aqueous medium. Furthermore, the reaction of the oximic hydrazone (H(2)L) with copper(II)-nitrate and chloride in addition to copper(I)-iodide afforded square planar mononuclear and binuclear complexes in which the oximic hydrazone showed three different modes of bonding. The obtained complexes reflect the strong bridging ability of the oximato group as well as its ambidentate and flexidentate characters. Copyright 2010 Elsevier B.V. All rights reserved.

In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase

PubMed Central

Jun, Daniel; Musilova, Lucie; Musilek, Kamil; Kuca, Kamil

2011-01-01

We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to reactivate human acetylcholinesterase (AChE), inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos). We also tested reactivation of human butyrylcholinesterase (BChE) with the aim of finding a potent oxime, suitable to serve as a “pseudocatalytic” bioscavenger in combination with this enzyme. Such a combination could allow an increase of prophylactic and therapeutic efficacy of the administered enzyme. According to our results, the best broad-spectrum AChE reactivators were trimedoxime and obidoxime in the case of paraoxon, leptophos-oxon, and methamidophos-inhibited AChE. Methamidophos and leptophos-oxon were quite easily reactivatable by all tested reactivators. In the case of methamidophos-inhibited AChE, the lower oxime concentration (10−5 M) had higher reactivation ability than the 10−4 M concentration. Therefore, we evaluated the reactivation ability of obidoxime in a concentration range of 10−3–10−7 M. The reactivation of methamidophos-inhibited AChE with different obidoxime concentrations resulted in a bell shaped curve with maximum reactivation at 10−5 M. In the case of BChE, no reactivator exceeded 15% reactivation ability and therefore none of the oximes can be recommended as a candidate for “pseudocatalytic” bioscavengers with BChE. PMID:21673941

Synthesis, X-ray crystallography, spectroscopic (FT-IR, 1H &13C NMR and UV), computational (DFT/B3LYP) and enzymes inhibitory studies of 7-hydroximinocholest-5-en-3-ol acetate

NASA Astrophysics Data System (ADS)

Ahmad, Faheem; Parveen, Mehtab; Alam, Mahboob; Azaz, Shaista; Malla, Ali Mohammed; Alam, Mohammad Jane; Lee, Dong-Ung; Ahmad, Shabbir

2016-07-01

The present study reports the synthesis of 7-Hydroximinocholest-5-en-3-ol acetate (syn. 3β-acetoxycholest-5-en-7-one oxime; in general, steroidal oxime). The identity of steroidal molecule was confirmed by NMR, FT-IR, MS, CHN microanalysis and X-ray crystallography. DFT calculations on the titled molecule have been performed. The molecular structure and spectra interpreted by Gaussian hybrid computational analysis theory (B3LYP) are found to be in good correlation with the experimental data obtained from the various spectrophotometric techniques. The vibrational bands appearing in the FTIR are assigned with great accuracy using harmonic frequencies along with intensities and animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural atomic charges have been presented at the same level of theory. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The percentages of various interactions are pictorialized by fingerprint plots of Hirshfeld surface. Steroidal oxime exhibited promising inhibitory activity against acetylcholinesterase (AChE) as compared to the reference drug, tacrine. Molecular docking was performed to introduce steroidal molecules into the X-ray crystal structures of acetylcholinesterase at the active site to find out the probable binding mode. The results of molecular docking admitted that steroidal oxime may exhibit enzyme inhibitor activity.

Kinetic analysis of interactions of paraoxon and oximes with human, Rhesus monkey, swine, rabbit, rat and guinea pig acetylcholinesterase.

PubMed

Worek, Franz; Aurbek, Nadine; Wille, Timo; Eyer, Peter; Thiermann, Horst

2011-01-15

Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. These findings provoked the present in vitro study which was designed to determine the inhibition, aging, spontaneous and oxime-induced reactivation kinetics of the pesticide paraoxon, serving as a model compound for diethyl-OP, and the oximes obidoxime, pralidoxime, HI 6 and MMB-4 with human, Rhesus monkey, swine, rabbit, rat and guinea pig erythrocyte AChE. Comparable results were obtained with human and monkey AChE. Differences between human, swine, rabbit, rat and guinea pig AChE were determined for the inhibition and reactivation kinetics. A six-fold difference of the inhibitory potency of paraoxon with human and guinea pig AChE was recorded while only moderate differences of the reactivation constants between human and animal AChE were determined. Obidoxime was by far the most effective reactivator with all tested species. Only minor species differences were found for the aging and spontaneous reactivation kinetics. The results of the present study underline the necessity to determine the inhibition, aging and reactivation kinetics in vitro as a basis for the development of meaningful therapeutic animal models, for the proper assessment of in vivo animal data and for the extrapolation of animal data to humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Theoretical investigations on the mechanism of benzoin condensation catalyzed by pyrido[1,2-a]-2-ethyl[1,2,4]triazol-3-ylidene.

PubMed

He, Yunqing; Xue, Ying

2011-03-03

A new annulated N-heterocyclic carbene (NHC), pyrido[1,2-a]-2-ethyl[1,2,4]triazol-3-ylidene, has been synthesized and its good catalytic activity for benzoin condensation has been experimentally determined by You and co-workers recently [ Ma , Y. J. , Wei , S. P. , Lan , J. B. , Wang , J. Z. , Xie , R. G. , and You , J. S. J. Org. Chem. 2008 , 73 , 8256 ]. In this work, the mechanism of the title reaction has been intensively studied computationally by employing the density functional theory (B3LYP) method in conjunction with 6-31+G(d) and 6-311+G(2d,p) basis sets. Our results indicate that path A (in which a sequence of intermolecular proton transfers between two carbene/benzaldehyde coupling intermediates affords enamine) and path B (in which a t-BuOH assisted hydrogen transfer generates enamine) proposed on the basis of the Breslow mechanism are competitive for their similar barriers. In path A, the first intermolecular proton transfer between two N-heterocyclic carbene/benzaldehyde coupled intermediates to form tertiary alcohol and enolate anion is theoretically the rate-determining step with corresponding barrier (30.93 kcal/mol), while the t-BuOH assisted hydrogen transfer generating Breslow enamine is the rate-determining step with corresponding barrier (28.84 kcal/mol) in path B. The coupling of carbene and benzaldehyde, and the coupling of enamine and another benzaldehyde to form a C-C bond are partially rate-determining for their relatively significant barriers (24.06 and 26.95 kcal/mol, respectively), being the same in both paths A and B. Our results are in nice agreement with the experimental result in a kinetic investigation of thiazolium ion-catalyzed benzoin condensation performed by White and Leeper in 2001.

Polystyrene bound oxidovanadium(IV) and dioxidovanadium(V) complexes of histamine derived ligand for the oxidation of methyl phenyl sulfide, diphenyl sulfide and benzoin.

PubMed

Maurya, Mannar R; Arya, Aarti; Kumar, Amit; Pessoa, João Costa

2009-03-28

Ligand Hsal-his (I) derived from salicylaldehyde and histamine has been covalently bound to chloromethylated polystyrene cross-linked with 5% divinylbenzene. Upon treatment with [VO(acac)(2)] in DMF, the polystyrene-bound ligand (abbreviated as PS-Hsal-his, II) gave the stable polystyrene-bound oxidovanadium(iv) complex PS-[V(IV)O(sal-his)(acac)] , which upon oxidation yielded the dioxidovanadium(v) PS-[V(V)O(2)(sal-his)] complex. The corresponding non polymer-bound complexes [V(IV)O(sal-his)(acac)] and [V(V)O(2)(sal-his)] have also been obtained. These complexes have been characterised by IR, electronic, (51)V NMR and EPR spectral studies, and thermal as well as scanning electron micrograph studies. Complexes and have been used as a catalyst for the oxidation of methyl phenyl sulfide, diphenyl sulfide and benzoin with 30% H(2)O(2) as oxidant. Under the optimised reaction conditions, a maximum of 93.8% conversion of methyl phenyl sulfide with 63.7% selectivity towards methyl phenyl sulfoxide and 36.3% towards methyl phenyl sulfone has been achieved in 2 h with 2 . Under similar conditions, diphenyl sulfide gave 83.4% conversion where selectivity of reaction products varied in the order: diphenyl sulfoxide (71.8%) > diphenyl sulfone (28.2%). A maximum of 91.2% conversion of benzoin has been achieved within 6 h, and the selectivities of reaction products are: methylbenzoate (37.0%) > benzil (30.5%) > benzaldehyde-dimethylacetal (22.5%) > benzoic acid (8.1%). The PS-bound complex, 1 exhibits very comparable catalytic potential. These polymer-anchored heterogeneous catalysts do not leach during catalytic action, are recyclable and show higher catalytic activity and turnover frequency than the corresponding non polymer-bound complexes. EPR and (51)V NMR spectroscopy was used to characterise methanolic solutions of 3 and 4 and to identify species formed upon addition of H(2)O(2) and/or acid and/or methyl phenyl sulfide.

Acclimation of respiratory O{sub 2} uptake in green tissues of field-grown native species after long-term exposure to elevated atmospheric CO{sub 2}

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

Azcon-Bieto, J.; Gonzalez-Meler, M.A.; Doherty, W.

1994-11-01

C{sub 3} and C{sub 4} plants were grown in open-top chambers in the field at two CO{sub 2} concentrations, normal ambient (ambient) and normal ambient + 340 {mu}L L{sup {minus}1} (elevated). Dark oxygen uptake was measured in leaves and stems using a liquid-phase Clark-type oxygen electrode. High CO{sub 2} treatment decreased dark oxygen uptake in stems of Scirpus olneyi (C{sub 3}) and leaves of Lindera benzoin (C{sub 3}) expressed on either a dry weight or area basis. Respiration of Spartina patens (C{sub 4}) leaves was unaffected by CO{sub 2} treatment. Leaf dry weight per unit area was unchanged by CO{submore » 2}, but respiration per unit of carbon or per unit of nitrogen was decreased in the C{sub 3} species grown at high CO{sub 2}. The component of respiration in stems of S. olneyi and leaves of L. benzoin primarily affected by long-term exposure to the elevated CO{sub 2} treatment was the activity of the cytochrome pathway. Elevated CO{sub 2} had no effect on activity and capacity of the alternative pathway in S. olneyi. The cytochrome c oxidase activity, assayed in a cell-free extract, was strongly decreased by growth at high CO{sub 2} in stems of S. olneyi but it was unaffected in S. patens leaves. The activity of cytochrome c oxidase and complex III extracted from mature leaves of L. benzoin was also decreased after one growing season of plant exposure to elevated CO{sub 2} concentration. These results show that in some C{sub 3} species respiration will be reduced when plants are grown in elevated atmospheric CO{sub 2}. The possible physiological causes and implications of these effects are discussed. 34 refs., 1 fig., 6 tabs.« less

Benzoin Condensation: Monitoring a Chemical Reaction by High-Pressure Liquid Chromatography

ERIC Educational Resources Information Center

Bhattacharya, Apurba; Purohit, Vikram C.; Bellar, Nicholas R.

2004-01-01

High-pressure liquid chromatography (HPLC) is the preferred method of separating a variety of materials in complex mixtures such as pharmaceuticals, polymers, soils, food products and biological fluids and is also considered to be a powerful analytical tool in both academia and industry. The use of HPLC analysis as a means of monitoring and…

Biomass conversion to high value chemicals: from furfural to chiral hydrofuroins in two steps.

PubMed

Kabro, Anzhelika; Escudero-Adán, Eduardo C; Grushin, Vladimir V; van Leeuwen, Piet W N M

2012-08-03

Catalytic asymmetric transfer hydrogenation of rac-furoin and furil produces hydrofuroin with up to 99% ee and 9:1 dr. This reaction provides an exceptionally easy access to optically active hydrofuroins in two straightforward steps from biomass-derived furfural (global production 200,000-300,000 t annually) using benzoin condensation.

Undergraduate Separations Utilizing Flash Chromatography

NASA Astrophysics Data System (ADS)

Horowitz, G.

2000-02-01

This article describes the procedures used to carry out four flash chromatography experiments: the isolation of the carotenes, chlorophylls and xanthophylls from a spinach extract; the separation of ß-carotene from tetraphenyl cyclopentadienone; the isolation of (+) and (-) carvone from caraway and spearmint oil; and the purification of benzil from benzoin. Apparatus used is nonbreakable, easy to use, and inexpensive.

Functionalized nanoparticles for AMF-induced gene and drug delivery

NASA Astrophysics Data System (ADS)

Biswas, Souvik

The properties and broad applications of nano-magnetic colloids have generated much interest in recent years. Specially, Fe3O4 nanoparticles have attracted a great deal of attention since their magnetic properties can be used for hyperthermia treatment or drug targeting. For example, enhanced levels of intracellular gene delivery can be achieved using Fe3O4 nano-vectors in the presence of an external magnetic field, a process known as 'magnetofection'. The low cytotoxicity, tunable particle size, ease of surface functionalization, and ability to generate thermal energy using an external alternating magnetic field (AMF) are properties have propelled Fe3O4 research to the forefront of nanoparticle research. The strategy of nanoparticle-mediated, AMF-induced heat generation has been used to effect intracellular hyperthermia. One application of this 'magnetic hyperthermia' is heat activated local delivery of a therapeutic effector (e.g.; drug or polynucleotide). This thesis describes the development of a magnetic nano-vector for AMF-induced, heat-activated pDNA and small molecule delivery. The use of heat-inducible vectors, such as heat shock protein ( hsp) genes, is a promising mode of gene therapy that would restrict gene expression to a local region by focusing a heat stimulus only at a target region. We thus aimed to design an Fe3O4 nanoparticle-mediated gene transfer vehicle for AMF-induced localized gene expression. We opted to use 'click' oximation techniques to assemble the magnetic gene transfer vector. Chapter 2 describes the synthesis, characterization, and transfection studies of the oxime ether lipid-based nano-magnetic vectors MLP and dMLP. The synthesis and characterization of a novel series of quaternary ammonium aminooxy reagents (2.1--2.4) is described. These cationic aminooxy compounds were loaded onto nanoparticles for ligation with carbonyl groups and also to impart a net positive charge on the nanoparticle surface. Our studies indicated that the non-toxic magnetoplexes (magnetic nanoparticle + pDNA complex) derived from dMLP deliver pDNA into mammalian cells even without external magnetic assistance. To date, dMLP is the only polymer-free magnetic gene delivery system that can deliver pDNA without any magnetic assistance. Chapter 3 of this thesis outlines the synthesis and characterization of other oxime ether lipids and details studies using derived-lipoplexes. These lipids were evaluated in pDNA and siRNA transfection studies in various mammalian cell lines. This work constitutes the first use of an oxime ether as the linking domain in cationic transfection lipids. These biocompatible oxime ether lipids can be readily assembled by click chemistry through ligation of hydrophobic aldehydes with quaternary ammonium aminooxy salts. Our studies showed that the oxime ether lipids transfected pDNA and siRNA efficiently in MCF-7, H 1792, and in PAR C10 cells comparable to and in some cases better than commercial transfection lipids. Chapter 4 describes the design and characterization of a nano-magnetic delivery system for AMF-induced drug (doxorubicin) release. In efforts to develop a magnetic formulation free from thermosensitive materials, such as hydrogels, we synthesized three nanoparticle-based doxorubicin formulations using charge interactions as the key associative force. To do so, we synthesized and characterized a novel cationic oxime ether conjugate at C-13 of doxorubicin. Our investigation indicated that the positive charge of the oxime ether drug conjugate tended to bind better to the negatively charged nanoparticle than did the other formulations prepared in stepwise manner. Our findings show that the nano-magnetic formulations remained essestially inactive at body temperature (37.5 °C) and released a majority of the cargo only when exposed to an external AMF. Our designed magnetic drug delivery platform is the first example of an AMF-inducible system that does not depend on the inclusion of thermosensitive materials. Finally, we have developed a bioanalytical application of the highly chemoselective oximation chemistry using aminooxy reagent 2.1. Chapter 5 describes a silica microchip containing micropillars coated with cationic aminooxy reagent 2.1. The microchip captures gaseous ketones and aldehydes from exhaled human breath. A brief description of microchip fabricated breath analyzer and breath analysis is described in Chapter 5. Our studies showed that the acetone capture efficiency of the aminooxy-loaded microchip was 98%.

Pro-2-PAM Therapy for Central and Peripheral Cholinesterases

PubMed Central

DeMar, James C.; Clarkson, Edward D.; Ratcliffe, Ruthie H.; Campbell, Amy J.; Thangavelu, Sonia G.; Herdman, Christine A.; Leader, Haim; Schulz, Susan M.; Marek, Elizabeth; Medynets, Marie A.; Ku, Theresa C.; Evans, Sarah A.; Khan, Farhat A.; Owens, Roberta R.; Nambiar, Madhusoodana P.; Gordon, Richard K.

2010-01-01

Novel therapeutics to overcome the toxic effects of organophosphorus (OP) chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980–1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP exposure therapy in the United States consists of atropine sulfate (to block muscarinic receptors), the acetylcholinesterase (AChE) reactivator (oxime) pralidoxime chloride (2-PAM), and a benzodiazepine anticonvulsant to ameliorate seizures. A major disadvantage is that quaternary nitrogen charged oximes, including 2-PAM, do not cross the blood brain barrier (BBB) to treat brain AChE. Therefore, we have synthesized and evaluated pro-2-PAM (a lipid permeable 2-PAM derivative) that can enter the brain and reactivate CNS AChE, preventing seizures in guinea pigs after exposure to OPs. The protective effects of the pro-2-PAM after OP exposure were shown using a) surgically-implanted radiotelemetry probes for electroencephalogram (EEG) b) neurohistopathology of brain, c) cholinesterase activities in the PNS and CNS, and d) survivability. The PNS oxime 2-PAM was ineffective at reducing seizures/status epilepticus (SE) in diisopropyl-fluorophosphate (DFP)-exposed animals. In contrast, pro-2-PAM significantly suppressed and then eliminated seizure activity. In OP-exposed guinea pigs, there was a significant reduction in neurological damage with pro-2-PAM, but not 2-PAM. Distinct regional areas of the brains showed significantly higher AChE activity 1.5 h after OP exposure in pro-2-PAM treated animals compared to the 2-PAM treated ones. However, blood and diaphragm showed similar AChE activities in animals treated with either oxime, as both 2-PAM and pro 2-PAM are PNS active oximes. In conclusion, pro-2-PAM can cross the BBB, is rapidly metabolized inside the brain to 2-PAM, and protects against OP-induced SE through restoration of brain AChE activity. Pro-2-PAM represents the first non-invasive means of administering a CNS therapeutic for the deleterious effects of OP poisoning by reactivating CNS AChE. PMID:20156430

Experimental and theoretical vibrational spectroscopy studies of acetohydroxamic acid and desferrioxamine B in aqueous solution: Effects of pH and iron complexation

NASA Astrophysics Data System (ADS)

Edwards, David C.; Nielsen, Steen B.; Jarzęcki, Andrzej A.; Spiro, Thomas G.; Myneni, Satish C. B.

2005-07-01

The deprotonation and iron complexation of the hydroxamate siderophore, desferrioxamine B (desB), and a model hydroxamate ligand, acetohydroxamic acid (aHa), were studied using infrared, resonance Raman and UV-vis spectroscopy. The experimental spectra were interpreted by a comparison with DFT calculated spectra of aHa (partly hydrated) and desB (reactive groups of unhydrated molecule) at the B3LYP/6-31G* level of theory. The ab initio models include three water molecules surrounding the deprotonation site of aHa to account for partial hydration. Experiments and calculations were also conducted in D 2O to verify spectral assignments. These studies of aHa suggest that the cis-keto-aHa is the dominant form, and its deprotonation occurs at the oxime oxygen atom in aqueous solutions. The stable form of iron-complexed aHa is identified as Fe(aHa) 3 for a wide range of pH conditions. The spectral information of aHa and an ab initio model of desB were used to interpret the chemical state of different functional groups in desB. Vibrational spectra of desB indicate that the oxime and amide carbonyl groups can be identified unambiguously. Vibrational spectral analysis of the oxime carbonyl after deprotonation and iron complexation of desB indicates that the conformational changes between anion and the iron-complexed anion are small. Enhanced electron delocalization in the oxime group of Fe-desB when compared to that of Fe(aHa) 3 may be responsible for higher stability constant of the former.

Pseudocatalytic scavenging of the nerve agent VX with human blood components and the oximes obidoxime and HI-6.

PubMed

Wille, Timo; von der Wellen, Jens; Thiermann, Horst; Worek, Franz

2017-03-01

Despite six decades of extensive research in medical countermeasures against nerve agent poisoning, a broad spectrum acetylcholinesterase (AChE) reactivator is not yet available. One current approach is directed toward synthesizing oximes with high affinity and reactivatability toward butyrylcholinesterase (BChE) in plasma to generate an effective pseudocatalytic scavenger. An interim solution could be the administration of external AChE or BChE from blood products to augment pseudocatalytic scavenging with slower but clinically approved oximes to decrease nerve agent concentrations in the body. We here semiquantitatively investigate the ability of obidoxime and HI-6 to decrease the inhibitory activity of VX with human AChE and BChE from whole blood, erythrocyte membranes, erythrocytes, plasma, clinically available fresh frozen plasma and packed red blood cells. The main findings are that whole blood showed a VX concentration-dependent decrease in inhibitory activity with HI-6 being more potent than obidoxime. Using erythrocytes and erythrocyte membranes again, HI-6 was more potent compared to obidoxime. With freshly prepared plasma, obidoxime and HI-6 showed comparable results for the decrease in VX. The use of the clinically available blood products revealed that packed red blood cells showed similar kinetics as fresh erythrocytes. Fresh frozen plasma resulted in a slower and incomplete decrease in inhibitory plasma compared to freshly prepared plasma. In conclusion, the administration of blood products in combination with available oximes augments pseudocatalytic scavenging and might be useful to decrease the body load of persistent, highly toxic nerve agents.

Utilization of Nitrophenylphosphates and Oxime-Based Ligation for the Development of Nanomolar Affinity Inhibitors of the Yersinia Pestis Outer Protein H (YopH) Phosphatase†, §, ¶

PubMed Central

Bahta, Medhanit; Lountos, George T.; Dyas, Beverly; Kim, Sung-Eun; Ulrich, Robert G.; Waugh, David S.; Burke, Terrence R.

2011-01-01

Our current study reports the first KM optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (KM = 80 μM was converted from a substrate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid and by attachment of an aminooxy handle for further structural optimization by oxime-ligation. A co-crystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequently employed for the design of furanyl-based oxime derivatives. By this process, a potent (IC50 = 190 nM) and non-promiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition of intracellular Y. pestis replication at a non-cytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH. PMID:21443195

Synthesis and in-vitro reactivation screening of imidazolium aldoximes as reactivators of sarin and VX-inhibited human acetylcholinesterase (hAChE).

PubMed

Sharma, Rahul; Gupta, Bhanushree; Sahu, Arvind Kumar; Acharya, Jyotiranjan; Satnami, Manmohan L; Ghosh, Kallol K

2016-11-25

Post-treatment of organophosphate (OP) poisoning involves the application of oxime reactivator as an antidote. Structurally different oximes are widely studied to examine their kinetic and mechanistic behavior against OP-inhibited cholinesterase enzyme. A series of structurally related 1,3-disubstituted-2-[(hydroxyiminomethyl)alkyl]imidazolium halides (5a-5e, 9a-9c) were synthesized and further evaluated for their in-vitro reactivation ability to reactivate sarin- and VX-inhibited human acetylcholinesterase (hAChE). The observed results were compared with the reactivation efficacy of standard reactivators; 2-PAM, obidoxime and HI-6. Amongst the synthesized oximes, 5a, 9a and 9b were found to be most potent reactivators against sarin-inhibited hAChE while in case of VX only 9a exhibited comparable reactivity with 2-PAM. Incorporation of pyridinium ring to the imidazole ring resulted in substantial increase in the reactivation strength of prepared reactivator. Physicochemical properties of synthesized reactivators have also been evaluated. Copyright © 2016. Published by Elsevier Ireland Ltd.

Syntheses, crystal structures and characterization of nitrogen-rich salts based on bis (1H-tetrazol-5-yl) methanone oxime

NASA Astrophysics Data System (ADS)

Lin, Xinyu; Guo, Weiming; Zhang, Tianhe; Huang, Jingru; Tong, Yi; Zhang, Tonglai

2017-08-01

Two nitrogen-rich energetic salts (NH4)2(bto) (1) and (NH3OH)2(bto)·H2O (2) [H2bto = Bis (1H-tetrazol-5-yl) methanone oxime] were synthesized by an improved method in which water was used as solvent. These compounds were characterized by FT-IR spectroscopy, elemental analysis and single crystal X-ray diffraction. Their crystal structures were confirmed to belong to monoclinic system with space group P21 for 1 and Pc for 2, respectively. The detailed thermal behaviours were investigated by using differential scanning calorimetry (DSC) and thermogravimetric method (TG) (decomposition temperature >250 °C). The enthalpies of formation were calculated through the experimental values of combustion enthalpy. In addition, the sensitivities toward impact and friction were tested with standard methods, and those results indicated that two compounds are all insensitive (impact >40 J and friction >360 N). In short, both of the compounds show potential usages as energetic materials. The improved process opens a door for exploring nitrogen-rich salts based on Bis (1H-tetrazol-5-yl) methanone oxime.

Zebrafish as a model for acetylcholinesterase-inhibiting organophosphorus agent exposure and oxime reactivation

PubMed Central

Koenig, Jeffrey A.; Dao, Thuy L.; Kan, Robert K.; Shih, Tsung-Ming

2016-01-01

The current research progression efforts for investigating novel treatments for exposure to organophosphorus (OP) compounds that inhibit acetylcholinesterase (AChE), including pesticides and chemical warfare nerve agents (CWNAs), rely solely on in vitro cell assays and in vivo rodent models. The zebrafish (Danio rerio) is a popular, well-established vertebrate model in biomedical research that offers high-throughput capabilities and genetic manipulation not readily available with rodents. A number of research studies have investigated the effects of subacute developmental exposure to OP pesticides in zebrafish, observing detrimental effects on gross morphology, neuronal development, and behavior. Few studies, however, have utilized this model to evaluate treatments, such as oxime reactivators, anticholinergics, or anticonvulsants, following acute exposure. Preliminary work has investigated the effects of CWNA exposure. The results clearly demonstrated relative toxicity and oxime efficacy similar to that reported for the rodent model. This review surveys the current literature utilizing zebrafish as a model for OP exposure and highlights its potential use as a high-throughput system for evaluating AChE reactivator antidotal treatments to acute pesticide and CWNA exposure. PMID:27123828

Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning.

PubMed

Masson, Patrick; Nachon, Florian

2017-08-01

Organophosphorus agents (OPs) irreversibly inhibit acetylcholinesterase (AChE) causing a major cholinergic syndrome. The medical counter-measures of OP poisoning have not evolved for the last 30 years with carbamates for pretreatment, pyridinium oximes-based AChE reactivators, antimuscarinic drugs and neuroprotective benzodiazepines for post-exposure treatment. These drugs ensure protection of peripheral nervous system and mitigate acute effects of OP lethal doses. However, they have significant limitations. Pyridostigmine and oximes do not protect/reactivate central AChE. Oximes poorly reactivate AChE inhibited by phosphoramidates. In addition, current neuroprotectants do not protect the central nervous system shortly after the onset of seizures when brain damage becomes irreversible. New therapeutic approaches for pre- and post-exposure treatments involve detoxification of OP molecules before they reach their molecular targets by administrating catalytic bioscavengers, among them phosphotriesterases are the most promising. Novel generation of broad spectrum reactivators are designed for crossing the blood-brain barrier and reactivate central AChE. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

Determination of Carbonyl Functional Groups in Bio-oils by Potentiometric Titration: The Faix Method

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

Black, Stuart; Ferrell, Jack R.

We know that carbonyl compounds, present in bio-oils, are responsible for bio-oil property changes upon storage and during upgrading. Specifically, carbonyls cause an increase in viscosity (often referred to as 'aging') during storage of bio-oils. As such, carbonyl content has previously been used as a method of tracking bio-oil aging and condensation reactions with less variability than viscosity measurements. In addition, carbonyls are also responsible for coke formation in bio-oil upgrading processes. Given the importance of carbonyls in bio-oils, accurate analytical methods for their quantification are very important for the bio-oil community. Potentiometric titration methods based on carbonyl oximation havemore » long been used for the determination of carbonyl content in pyrolysis bio-oils. Here, we present a modification of the traditional carbonyl oximation procedures that results in less reaction time, smaller sample size, higher precision, and more accurate carbonyl determinations. And while traditional carbonyl oximation methods occur at room temperature, the Faix method presented here occurs at an elevated temperature of 80 degrees C.« less

Design and Biological Evaluation of Antifouling Dihydrostilbene Oxime Hybrids.

PubMed

Moodie, Lindon W K; Cervin, Gunnar; Trepos, Rozenn; Labriere, Christophe; Hellio, Claire; Pavia, Henrik; Svenson, Johan

2018-04-01

By combining the recently reported repelling natural dihydrostilbene scaffold with an oxime moiety found in many marine antifoulants, a library of nine antifouling hybrid compounds was developed and biologically evaluated. The prepared compounds were shown to display a low antifouling effect against marine bacteria but a high potency against the attachment and growth of microalgae down to MIC values of 0.01 μg/mL for the most potent hybrid. The mode of action can be characterized as repelling via a reversible non-toxic biostatic mechanism. Barnacle cyprid larval settlement was also inhibited at low μg/mL concentrations with low levels or no toxicity observed. Several of the prepared compounds performed better than many reported antifouling marine natural products. While several of the prepared compounds are highly active as antifoulants, no apparent synergy is observed by incorporating the oxime functionality into the dihydrostilbene scaffold. This observation is discussed in light of recently reported literature data on related marine natural antifoulants and antifouling hybrids as a potentially general strategy for generation of improved antifoulants.

Divergent and convergent synthesis of GalNAc-conjugated dendrimers using dual orthogonal ligations.

PubMed

Thomas, Baptiste; Pifferi, Carlo; Daskhan, Gour Chand; Fiore, Michele; Berthet, Nathalie; Renaudet, Olivier

2015-12-21

The synthesis of glycodendrimers remains a challenging task. In this paper we propose a protocol based on both oxime ligation (OL) to combine cyclopeptide repeating units as the dendritic core and the copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) to conjugate peripheral α and β propargylated GalNAc. By contrast with the oxime-based iterative protocol reported in our group, our current strategy can be used in both divergent and convergent routes with similar efficiency and the resulting hexadecavalent glycodendrimers can be easily characterized compared to oxime-linked analogues. A series of glycoconjugates displaying four or sixteen copies of both α and β GalNAc have been prepared and their ability to inhibit the adhesion of the soybean agglutinin (SBA) lectin to polymeric-GalNAc immobilized on microtiter plates has been evaluated. As was anticipated, the higher inhibitory effect (IC50 = 0.46 μM) was measured with the structure displaying αGalNAc with the higher valency (compound 13), which demonstrates that the binding properties of these glycoconjugates are strongly dependent on the orientation and distribution of the GalNAc units.

Synthesis and mechanistic studies of curcumin analog-based oximes as potential anticancer agents.

PubMed

Qin, Hua-Li; Leng, Jing; Youssif, Bahaa G M; Amjad, Muhammad Wahab; Raja, Maria Abdul Ghafoor; Hussain, Muhammad Ajaz; Hussain, Zahid; Kazmi, Syeda Naveed; Bukhari, Syed Nasir Abbas

2017-09-01

The incidence of cancer can be decreased by chemoprevention using either natural or synthetic agents. Apart from synthetic compounds, numerous natural products have exhibited promising potential to inhibit carcinogenesis in vivo. In this study, α, β-unsaturated carbonyl-based anticancer compounds were used as starting materials to synthesize new oxime analogs. The findings from the antiproliferative assay using seven different human cancer cell lines provided a clear picture of structure-activity relationship. The oxime analogs namely 7a and 8a showed strong antiproliferative activity against the cell lines. The mechanistic effects of compounds on EGFR-TK kinases and tubulin polymerization and BRAF V 600E were investigated. In addition, the efficacy of compounds in reversing the efflux-mediated resistance developed by cancer cells was also studied. The compounds 5a and 6a displayed potent activity on various targets such as BRAF V 600E and EGFR-TK kinases and also exhibited strong antiproliferative activity against different cell lines hence showing potential of multifunctional anticancer agents. © 2017 John Wiley & Sons A/S.

Determination of Carbonyl Functional Groups in Bio-oils by Potentiometric Titration: The Faix Method

DOE PAGES

Black, Stuart; Ferrell, Jack R.

2017-02-07

We know that carbonyl compounds, present in bio-oils, are responsible for bio-oil property changes upon storage and during upgrading. Specifically, carbonyls cause an increase in viscosity (often referred to as 'aging') during storage of bio-oils. As such, carbonyl content has previously been used as a method of tracking bio-oil aging and condensation reactions with less variability than viscosity measurements. In addition, carbonyls are also responsible for coke formation in bio-oil upgrading processes. Given the importance of carbonyls in bio-oils, accurate analytical methods for their quantification are very important for the bio-oil community. Potentiometric titration methods based on carbonyl oximation havemore » long been used for the determination of carbonyl content in pyrolysis bio-oils. Here, we present a modification of the traditional carbonyl oximation procedures that results in less reaction time, smaller sample size, higher precision, and more accurate carbonyl determinations. And while traditional carbonyl oximation methods occur at room temperature, the Faix method presented here occurs at an elevated temperature of 80 degrees C.« less

SAR by Oxime-Containing Peptide Libraries: Application to Tsg101 Ligand Optimization

PubMed Central

Liu, Fa; Stephen, Andrew G.; Waheed, Abdul A.; Aman, M. Javad; Freed, Eric O.; Fisher, Robert J.; Burke, Terrence R.

2008-01-01

HIV-1 viral assembly requires a direct interaction between a Pro-Thr-Ala-Pro (“PTAP”) motif in the viral protein Gag-p6 and the cellular endosomal sorting factor Tsg101. In an effort to develop competitive inhibitors of this interaction, an SAR study was conducted based on the application of post solid-phase oxime formation involving the sequential insertion of aminooxy-containing residues within a nonamer parent peptide followed by reaction with libraries of aldehydes. Approximately 15–20-fold enhancement in binding affinity was achieved by this approach. PMID:18655064

Application of oxime-diversification to optimize ligand interactions within a cryptic pocket of the polo-like kinase 1 polo-box domain.

PubMed

Zhao, Xue Zhi; Hymel, David; Burke, Terrence R

2016-10-15

By a process involving initial screening of a set of 87 aldehydes using an oxime ligation-based strategy, we were able to achieve a several-fold affinity enhancement over one of the most potent previously known polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors. This improved binding may result by accessing a newly identified auxiliary region proximal to a key hydrophobic cryptic pocket on the surface of the protein. Our findings could have general applicability to the design of PBD-binding antagonists. Published by Elsevier Ltd.

Visible-light-promoted and one-pot synthesis of phenanthridines and quinolines from aldehydes and O-acyl hydroxylamine.

PubMed

An, Xiao-De; Yu, Shouyun

2015-06-05

A one-pot synthesis of phenanthridines and quinolines from commercially available or easily prepared aldehydes has been reported. O-(4-Cyanobenzoyl)hydroxylamine was utilized as the nitrogen source to generate O-acyl oximes in situ with aldehydes catalyzed by Brønsted acid. O-Acyl oximes were then subjected to visible light photoredox catalyzed cyclization via iminyl radicals to furnish aza-arenes. A variety of phenanthridines and quinolines have been prepared assisted by Brønsted acid and photocatalyst under visible light at room temperature with satisfactory yields.

Computational investigations of trans-platinum(II) oxime complexes used as anticancer drug

NASA Astrophysics Data System (ADS)

Sayin, Koray; Karakaş, Duran

2018-01-01

Some platinum oxime complexes are optimized at HF/CEP-31G level which has been reported as the best level for these type complexes in the gas phase. IR spectrum is calculated and the new scale factor is derived. NMR spectrum is calculated at the same level of theory and examined in detail. Quantum chemical parameters which have been mainly used are investigated and their formulas are given in detail. Additionally, selected quantum chemical parameters of studied complexes are calculated. New theoretical IC50% formulas are derived and biological activity rankings of mentioned complexes are investigated.

40 CFR 60.489 - List of chemicals produced by affected facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... 75-07-0 Acetaldehyde. 107-89-1 Acetaldol. 60-35-5 Acetamide. 103-84-4 Acetanilide. 64-19-7 Acetic.... 119-53-9 Benzoin. 100-47-0 Benzonitrile. 119-61-9 Benzophenone. 98-07-7 Benzotrichloride. 98-88-4...-4 Bromonaphthalene. 106-99-0 Butadiene. 106-98-9 1-butene. 123-86-4 n-butyl acetate. 141-32-2 n...

First report of laurel wilt, caused by Raffaelea lauricola , on spicebush ( Lindera benzoin ) in South Carolina

Treesearch

S. W. Fraedrich; T. C. Harrington; B. A. McDaniel; G. S. Best

2016-01-01

Most members of the laurel family (Lauraceae) indigenous to the United States appear to be highly susceptible to laurel wilt, a disease caused by Raffaelea lauricola T.C. Harr., Aghayeva & Fraedrich, a fungal symbiont of the redbay ambrosia beetle (Xyleborus glabratus Eichhoff) (Fraedrich et al. 2008; Harrington et al. 2008). The beetle and fungus were...

AN INVESTIGATION OF THE BENZOIN METHOD FOR THE FLUORIMETRIC DETERMINATION OF BORON

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

Elliott, G.; Radley, J.A.

1961-01-01

The development of the boron -benzoin fluorescence at microgram concentrations of boron was investigated; a simple, but sensitive, fluorimeter was used. The development and decay of fluorescence intensity with time were observed in various solvents in the presence of different basic compounds. The fluorescence produced when formamide and its N-derivatives are used as the solvent media is stronger than that found when ethanol is used. A glycine buffer solution of pH 12.8 is effective in producing the correct conditions for developing fluorescence with ethanol as solvent, but is not effective in the formamide series of solvents. Isopropylamine and isobutylamine aremore » effective bases in both ethanol and the formamide series. For a series of solvents of a given chemical type, e.g., the formamides, there may be an increase in fluorescence intensity with dielectric constant, although this is not true for the alcohols. Oxygen has a pronounced inhibiting action on the development of fluorescence in ethanol, but has much less effect in formamide. There is a linear relationship between fluorescence intensity and amount of boron present in the range studied (0.05 to 0.5 - g). (auth)« less

Expedient synthesis of C-aryl carbohydrates by consecutive biocatalytic benzoin and aldol reactions.

PubMed

Hernández, Karel; Parella, Teodor; Joglar, Jesús; Bujons, Jordi; Pohl, Martina; Clapés, Pere

2015-02-16

The introduction of aromatic residues connected by a C-C bond into the non-reducing end of carbohydrates is highly significant for the development of innovative structures with improved binding affinity and selectivity (e.g., C-aril-sLex). In this work, an expedient asymmetric "de novo" synthetic route to new aryl carbohydrate derivatives based on two sequential stereoselectively biocatalytic carboligation reactions is presented. First, the benzoin reaction of aromatic aldehydes to dimethoxyacetaldehyde is conducted, catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I. Then, the α-hydroxyketones formed are reduced by using NaBH4 yielding the anti diol. After acetal hydrolysis, the aldol addition of dihydroxyacetone, hydroxyacetone, or glycolaldehyde catalyzed by the stereocomplementary D-fructose-6-phosphate aldolase and L-rhamnulose-1-phosphate aldolase is performed. Both aldolases accept unphosphorylated donor substrates, avoiding the need of handling the phosphate group that the dihydroxyacetone phosphate-dependent aldolases require. In this way, 6-C-aryl-L-sorbose, 6-C-aryl-L-fructose, 6-C-aryl-L-tagatose, and 5-C-aryl-L-xylose derivatives are prepared by using this methodology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intravenous application of HI-6 salts (dichloride and dimethansulphonate) in pigs: comparison with pharmacokinetics profile after intramuscular administration.

PubMed

Zdarova Karasova, Jana; Zemek, Filip; Kunes, Martin; Kvetina, Jaroslav; Chladek, Jaroslav; Jun, Daniel; Bures, Jan; Tachecí, Ilja; Kuca, Kamil

2013-01-01

Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.). This route of administration has also some disadvantages, and alternative strategies ought to be examined. We evaluated the pharmacokinetic profiles of two HI-6 salts after their intravenous (i.v.) administration, and compare the results with the known pharmacokinetics after i.m. administration. Pigs were administered with HI-6 salts (i.v), either HI-6 dichloride (10.71 mg/kg) or molar equivalent HI-6 dimethansulphonate (13.59 mg/kg). Doses of the HI-6 salts corresponded with a standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for one kilogram of body weight. The main pharmacokinetic parameters are comparable after i.v. and i.m. HI-6 administration. The compared pharmacokinetic parameters were half-life, terminal rate constant, mean residence time of the molecule in the body, clearance, and the apparent volume in the terminal phase. The bioavailability after i.m. administration was comparable with that of i.v.; these results suggest that the oxime is well released from the muscle depot. Significant differences were found in parameters Cmax and Tmax which are important in cases of emergency when rapidity and bioavailability are paramount for the success of treatment. I.v. administration should solve the problem of rapid clearance. Infusion or bolus administration may be considered as a logical subsequent step in oxime treatment strategy. The main advantage is in maintenance of an effective therapeutic plasma concentration, a more easily achievable effective therapeutic concentration, and fewer local adverse reactions.

Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats

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

Shih, T.M.

1993-12-31

The ability of three oximes, HI-6, MMB-4 and ICD-467, to reactivate cholinesterase (ChE) inhibited by the organophosphorus compound soman was compared in blood (plasma and erythrocytes), brain regions (including spinal cord) and peripheral tissues of rats. Animals were intoxicated with soman (100 ttg/kg. SC; equivalent to 0.9 x LDs0 dose) and treated 1 min later with one of these oximes (100 or 200 ttmo1/kg, IM). Toxic sign scores and total tissue ChE activities were determined 30 min later. Soman markedly inhibited ChE activity in blood (93 - 96%), brain regions (ranging from 78% to 95%), and all peripheral tissues (rangingmore » from 48.9% to 99.8%) except liver (11.9%). In blood, treatment with HI-6 or ICD-467 resulted in significant reactivation of soman-inhibited ChE. in contrast, MMB-4 was completely ineffective. HI-6 and ICD-467 were equally effective at the high dose. At the low dose ICD-467 treatment resulted in significantly higher plasma ChE than Hl-6 treatment, whereas HI-6 treatment resulted in higher erythrocyte ChE than ICD-467 treatment. However, none of these three oximesreactivated or protected soman-inhibited ChE in the brain. In all peripheral tissues (except liver) studied, MMB-4 was not effective. 111-6 reactivated soman-inhibited ChE in all tis- sues except lung, heart, and skeletal muscle. ICD-467 was highly effective in reactivating ChE in all tissues and afforded a complete recovery of ChE to control levels in Intercostal muscle and salivary gland. Oxime treatments did not modify the toxic scores produced by soman.« less

Thiazolylidene-catalyzed cleavage of methyl oleate-derived α-hydroxy ketone to the corresponding free aldehydes.

PubMed

Deruer, Elsa; Duguet, Nicolas; Lemaire, Marc

2015-08-10

The thiazolylidene-catalyzed cleavage of the α-hydroxy ketone derived from methyl oleate gave the corresponding aldehydes under nonoxidative conditions through a retro-benzoin process. The aldehydes produced are in equilibrium with their corresponding acyloins. To illustrate the synthetic utility of this protocol, the aldehydes were recovered by distillation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biological and nonbiological modifications of carbamates

PubMed Central

Knaak, James B.

1971-01-01

Methylcarbamate insecticides undergo hydrolysis, oxidation, dealkylation, and conjugation in animals, plants, and insects to form similar or identical products. Carbaryl is hydroxylated in biological systems to form hydroxy, dihydro-dihydroxy, and N-hydroxymethyl carbaryl and is hydrolysed to form 1-naphthol. The products are conjugated, stored, or excreted. Carbofuran is hydroxylated at the 3 position and propoxur at the 5 position to form hydroxylated derivatives. N-hydroxymethyl derivatives of these two carbamates may also be formed. Hydrolysis appears to be the major metabolic pathway of carbofuran in the animal. Aldicarb is oxidized to its sulfoxide and then hydrolysed to the oxime sulfoxide in animals and plants. Plants hydrolyse the oxime sulfoxide to form the corresponding aldehyde, which is an intermediate in the formation of 2-methyl-2-(methyl-sulfinyl)propanol. Methomyl, which is structurally similar to aldicarb, is metabolized in plants to acetonitrile, carbon dioxide, and methylamine. Bux and Meobal undergo hydrolysis and hydroxylation to form N-hydroxy methylcarbamates, as well as hydroxybutylphenyl and hydroxymethylphenyl methylcarbamates. Zectran, which contains a dimethylamino group, is converted to the methylamino, amino, and methylformamido derivatives by insects and plants. In soil and water, methylcarbamate insecticides are hydrolysed to their respective phenols or oximes. PMID:4999481

Utilization of Nitrophenylphosphates and Oxime-Based Ligation for the Development of Nanomolar Affinity Inhibitors of the Yersinia pestis Outer Protein H (YopH) Phosphatase

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

Bahta, Medhanit; Lountos, George T.; Dyas, Beverly

Our current study reports the first K{sub M} optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (K{sub M} = 80 {micro}M) was converted from a substrate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid and by attachment of an aminooxy handle for further structural optimization by oxime ligation. A cocrystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequently employedmore » for the design of furanyl-based oxime derivatives. By this process, a potent (IC{sub 50} = 190 nM) and nonpromiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition of intracellular Y. pestis replication at a noncytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH.« less

Chemoselective amide formation using O-(4-nitrophenyl)hydroxylamines and pyruvic acid derivatives.

PubMed

Kumar, Sonali; Sharma, Rashi; Garcia, Megan; Kamel, Joseph; McCarthy, Caroline; Muth, Aaron; Phanstiel, Otto

2012-12-07

A series of O-(4-nitrophenyl)hydroxylamines were synthesized from their respective oximes using a pulsed addition of excess NaBH(3)CN at pH 3 in 65-75% yield. Steric hindrance near the oxime functional group played a key role in both the ease by which the oxime could be reduced and the subsequent reactivity of the respective hydroxylamine. Reaction of the respective hydroxylamines with pyruvic acid derivatives generated the desired amides in good yields. A comparison of phenethylamine systems bearing different leaving groups revealed significant differences in the rates of these systems and suggested that the leaving group ability of the N-OR substituent plays an important role in determining their reactivity with pyruvic acid. Competition experiments (in 68% DMSO/phosphate buffered saline) using 1 equiv of N-phenethyl-O-(4-nitrophenyl)hydroxylamine and 2 equiv of pyruvic acid in the presence of other nucleophiles such as glycine, cysteine, phenol, hexanoic acid, and lysine demonstrated that significant chemoselectivity is present in this reaction. The results suggest that this chemoselective reaction can occur in the presence of excess α-amino acids, phenols, acids, thiols, and amines.

Comparison of human and guinea pig acetylcholinesterase sequences and rates of oxime-assisted reactivation.

PubMed

Cadieux, C Linn; Broomfield, Clarence A; Kirkpatrick, Melanie G; Kazanski, Meghan E; Lenz, David E; Cerasoli, Douglas M

2010-09-06

Poisoning via organophosphorus (OP) nerve agents occurs when the OP binds and inhibits the enzyme acetylcholinesterase (AChE). This enzyme is responsible for the metabolism of the neurotransmitter acetylcholine (ACh) which transmits signals between nerves and several key somatic regions. When AChE is inhibited, the signal initiated by ACh is not properly terminated. Excessive levels of ACh result in a cholinergic crisis, and in severe cases can lead to death. Current treatments for OP poisoning involve the administration of atropine, which blocks ACh receptors, and oximes, which reactivate AChE after inhibition. Efforts to improve the safety, efficacy, and broad spectrum utility of these treatments are ongoing and usually require the use of appropriate animal model systems. For OP poisoning, the guinea pig (Cavia porcellus) is a commonly used animal model because guinea pigs more closely mirror primate susceptibility to OP poisoning than do other animals such as rats and mice. This is most likely because among rodents and other small mammals, guinea pigs have a very low relative concentration of serum carboxylesterase, an enzyme known to bind OPs in vitro and to act as an endogenous bioscavenger in vivo. Although guinea pigs historically have been used to test OP poisoning therapies, it has been found recently that guinea pig AChE is substantially more resistant to oxime-mediated reactivation than human AChE. To examine the molecular basis for this difference, we reverse transcribed mRNA encoding guinea pig AChE, amplified the resulting cDNA, and sequenced this product. The nucleotide and deduced amino acid sequences of guinea pig AChE were then compared to the human version. Several amino acid differences were noted, and the predicted locations of these differences were mapped onto a structural model of human AChE. To examine directly how these differences affect oxime-mediated reactivation of AChE after inhibition by OPs, human and guinea pig red blood cell ghosts were prepared and used as sources of AChE, and the relative capacity of several different oximes to reactivate each OP-inhibited AChE were determined. The differences we report between human and guinea pig AChE raise additional concerns about the suitability of the guinea pig as an appropriate small animal model to approximate human responses to OP poisoning and therapies. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Photoremovable chiral auxiliary.

PubMed

Kammath, Viju Balachandran; Sebej, Peter; Slanina, Tomáš; Kříž, Zdeněk; Klán, Petr

2012-03-01

A new concept of a photoremovable chiral auxiliary (PCA), based on the chiral benzoin chromophore, is introduced. This moiety can control the asymmetric formation of a Diels-Alder adduct, and then be removed in a subsequent photochemical step in high chemical and quantum yields. Selective formation of the products at up to 96% ee was observed in the presence of a Lewis acid catalyst in the case of a 2-methoxybenzoinyl chiral auxiliary.

A dimethyl ketal-protected benzoin-based linker suitable for photolytic release of unprotected peptides.

PubMed

Chumachenko, Nataliya; Novikov, Yehor; Shoemaker, Richard K; Copley, Shelley D

2011-11-18

Photolabile 3',5'-dimethoxybenzoin-based linkers are advantageous for a variety of solid-phase synthetic procedures and manipulations of biomolecules because UV irradiation in aqueous media provides fast and essentially quantitative release of tethered molecules, while generating unreactive side products. Practical applications of previously reported linkers are compromised to some extent by the 1,3-dithiane protection of the benzoin carbonyl group and the lengthy synthesis. We have extended the group of photocleavable 3',5'-dimethoxybenzoin-based linkers by designing and synthesizing a linker in which the carbonyl group is protected as a dimethyl ketal. This protection is compatible with commonly used esterification and amide bond formation techniques, including the Fmoc/tBu strategy for solid phase peptide synthesis, is stable under mild acidic conditions, and can be quantitatively removed in <5 min by 3% TFA in dichloromethane. Irradiation of beads carrying peptides attached to the linker at 350 nm in aqueous or partially aqueous media affords >90% release after 30 min. The linker was synthesized from commercially available starting materials in five steps with an overall yield of 40% and without any column chromatography purification. Additionally, we developed a route to a dithiane-protected linker that requires only two steps and proceeds in 65% yield, a significant improvement over previous synthetic routes.

Study of Inhibition, Reactivation and Aging Processes of Pesticides Using Graphene Nanosheets/Gold Nanoparticles-Based Acetylcholinesterase Biosensor

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

Zhang, Lin; Long, Linjuan; Zhang, Weiying

2012-09-10

Organophosphate (OP) and carbamate pesticides exert their toxicity via attacking the hydroxyl moiety of serine in the 'active site' of acetylcholinesterase (AChE). In this paper we developed a stable AChE biosensor based on self-assembling AChE to graphene nanosheet (GN)-gold nanoparticles (AuNPs) nanocomposite electrode for investigation of inhibition, reactivation and aging processes of different pesticides. It is confirmed that pesticides can inhibit AChE in a short time. OPs poisoning is treatable with oximes while carbarmates exposure is insensitive to oximes. The proposed electrochemical approach thus provides a new simple tool for comparison of pesticide sensitivity and guide of therapeutic intervention.

Rapid kinetic characterization of glycosyl hydrolases based on oxime derivatization and nanostructure-initiator mass spectrometry (NIMS).

PubMed

Deng, Kai; Takasuka, Taichi E; Heins, Richard; Cheng, Xiaoliang; Bergeman, Lai F; Shi, Jian; Aschenbrener, Ryan; Deutsch, Sam; Singh, Seema; Sale, Kenneth L; Simmons, Blake A; Adams, Paul D; Singh, Anup K; Fox, Brian G; Northen, Trent R

2014-07-18

Glycoside hydrolases (GHs) are critical to cycling of plant biomass in the environment, digestion of complex polysaccharides by the human gut microbiome, and industrial activities such as deployment of cellulosic biofuels. High-throughput sequencing methods show tremendous sequence diversity among GHs, yet relatively few examples from the over 150,000 unique domain arrangements containing GHs have been functionally characterized. Here, we show how cell-free expression, bioconjugate chemistry, and surface-based mass spectrometry can be used to study glycoside hydrolase reactions with plant biomass. Detection of soluble products is achieved by coupling a unique chemical probe to the reducing end of oligosaccharides in a stable oxime linkage, while the use of (13)C-labeled monosaccharide standards (xylose and glucose) allows quantitation of the derivatized glycans. We apply this oxime-based nanostructure-initiator mass spectrometry (NIMS) method to characterize the functional diversity of GHs secreted by Clostridium thermocellum, a model cellulolytic organism. New reaction specificities are identified, and differences in rates and yields of individual enzymes are demonstrated in reactions with biomass substrates. Numerical analyses of time series data suggests that synergistic combinations of mono- and multifunctional GHs can decrease the complexity of enzymes needed for the hydrolysis of plant biomass during the production of biofuels.

Coordination properties of the oxime analogue of glycine to Cu(II).

PubMed

Georgieva, I; Trendafilova, N; Rodríguez-Santiago, L; Sodupe, M

2005-06-30

The coordination of Cu2+ by glyoxilic acid oxime (gao)--the oxime analogue of glycine amino acid--and its deprotonated (gao- and gao2-) species has been studied with different density functional methods. Single-point calculations have also been carried out at the single- and double- (triple) excitation coupled-cluster (CCSD(T)) level of theory. The isomers studied involve coordination of Cu2+ to electron-rich sites (O,N) of neutral, anionic, and dianionic gao species in different conformations. In contrast to Cu2+-glycine, for which the ground-state structure is bidentate with the CO2(-) terminus of zwitterionic glycine, for Cu2+-gao the most stable isomer shows monodentate binding of Cu2+ with the carbonylic oxygen of the neutral form. The most stable complexes of Cu2+ interacting with deprotonated gao species (gao- and gao2-) also take place through the carboxylic oxygens but in a bidentate manner. The results with different functionals show that, for these open shell (Cu2+-L) systems, the relative stability of complexes with different coordination environments (and so, different spin distribution) can be quite sensitive to the amount of "Hartree-Fock" exchange included in the functional. Among all the functionals tested in this work, the BHandHLYP is the one that better compares to CCSD(T) results.

An easy method for the determination of active concentrations of cholinesterase reactivators in blood samples: Application to the efficacy assessment of non quaternary reactivators compared to HI-6 and pralidoxime in VX-poisoned mice.

PubMed

Calas, André-Guilhem; Dias, José; Rousseau, Catherine; Arboléas, Mélanie; Touvrey-Loiodice, Mélanie; Mercey, Guillaume; Jean, Ludovic; Renard, Pierre-Yves; Nachon, Florian

2017-04-01

Organophosphorus nerve agents, like VX, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). AChE inhibited by VX can be reactivated using powerful nucleophilic molecules, most commonly oximes, which are one major component of the emergency treatment in case of nerve agent intoxication. We present here a comparative in vivo study on Swiss mice of four reactivators: HI-6, pralidoxime and two uncharged derivatives of 3-hydroxy-2-pyridinaldoxime that should more easily cross the blood-brain barrier and display a significant central nervous system activity. The reactivability kinetic profile of the oximes is established following intraperitoneal injection in healthy mice, using an original and fast enzymatic method based on the reactivation potential of oxime-containing plasma samples. HI-6 displays the highest reactivation potential whatever the conditions, followed by pralidoxime and the two non quaternary reactivators at the dose of 50 mg/kg bw. But these three last reactivators display equivalent reactivation potential at the same dose of 100 μmol/kg bw. Maximal reactivation potential closely correlates to surviving test results of VX intoxicated mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE).

PubMed

Karade, Hitendra N; Raviraju, G; Acharya, B N; Valiveti, Aditya Kapil; Bhalerao, Uma; Acharya, Jyotiranjan

2016-09-15

Previously (Karade et al., 2014), we have reported the synthesis and in vitro evaluation of bis-pyridinium derivatives of pyridine-3-yl-(2-hydroxyimino acetamide), as reactivators of sarin and VX inhibited hAChE. Few of the molecules showed superior in vivo protection efficacy (mice model) (Kumar et al., 2014; Swami et al., 2016) in comparison to 2-PAM against DFP and sarin poisoning. Encouraged by these results, herein we report the synthesis and in vitro evaluation of isonicotinamide derivatives of pyridine-3-yl-(2-hydroxyimino acetamide) (4a-4d) against sarin and VX inhibited erythrocyte ghost hAChE. Reactivation kinetics of these compounds was studied and the determined kinetic parameters were compared with that of commercial reactivators viz. 2-PAM and obidoxime. In comparison to 2-PAM and obidoxime, oxime 4a and 4b exhibited enhanced reactivation efficacy toward sarin inhibited hAChE while oxime 4c showed far greater reactivation efficacy toward VX inhibited hAChE. The acid dissociation constant and IC50 values of these oximes were determined and correlated with the observed reactivation potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of the oxime-induced reactivation of rhesus monkey, swine and guinea pig erythrocyte acetylcholinesterase following inhibition by sarin or paraoxon, using a perfusion model for the real-time determination of membrane-bound acetylcholinesterase activity.

PubMed

Herkert, Nadja M; Lallement, Guy; Clarençon, Didier; Thiermann, Horst; Worek, Franz

2009-04-28

Recently, a dynamically working in vitro model with real-time determination of membrane-bound human acetylcholinesterase (AChE) activity was shown to be a versatile model to investigate oxime-induced reactivation kinetics of organophosphate- (OP) inhibited enzyme. In this assay, AChE was immobilized on particle filters which were perfused with acetylthiocholine, Ellman's reagent and phosphate buffer. Subsequently, AChE activity was continuously analyzed in a flow-through detector. Now, it was an intriguing question whether this model could be used with erythrocyte AChE from other species in order to investigate kinetic interactions in the absence of annoying side reactions. Rhesus monkey, swine and guinea pig erythrocytes were a stable and highly reproducible enzyme source. Then, the model was applied to the reactivation of sarin- and paraoxon-inhibited AChE by obidoxime or HI 6 and it could be shown that the derived reactivation rate constants were in good agreement to previous results obtained from experiments with a static model. Hence, this dynamic model offers the possibility to investigate highly reproducible interactions between AChE, OP and oximes with human and animal AChE.

A facile and efficient synthesis of some (6E)-hydroximino-4-en-3-one steroids, steroidal oximes from Cinachyrella spp. sponges.

PubMed

Cui, Jianguo; Huang, Liliang; Fan, Lei; Zhou, Aimin

2008-03-01

Using beta-sitosterol as a starting material, (6E)-hydroximino-24-ethylcholest-4-en-3-one (1), a natural steroidal oxime from Cinachyrella alloclada and C. apion, was synthesized in four steps with a high overall yield. First, beta-sitosterol (5a) is transformed into the corresponding 24-ethylcholest-4-en-3,6-dione (6a) via oxidation with pyridinium chlorochromate (PCC). Selective reduction of 6a by NaBH(4) in the presence of CoCl(2) gives 24-ethylcholest- 4-en-3beta-ol-6-one (7a). The reaction of 7a with hydroxylamine hydrochloride offers the oxime 8a and the oxidation of 8a by Jones reagent gives the target steroid 1. (6E)-Hydroximinocholest-4-en-3-one (2) and (6E)-hydroximino-24-ethylcholest-4,22-dien-3-one (4) were synthesized by a similar method. The cytotoxicity of the synthesized compounds against sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells were investigated. The presence of a cholesterol-type side chain appears to be necessary for the biological activity.

Limitations and challenges in treatment of acute chemical warfare agent poisoning.

PubMed

Thiermann, Horst; Worek, Franz; Kehe, Kai

2013-12-05

Recent news from Syria on a possible use of chemical warfare agents made the headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts these agents into the public focus. For incidents with mass casualties appropriate medical countermeasures must be available. At present, the most important threats arise from nerve agents and sulfur mustard. At first, self-protection and protection of medical units from contamination is of utmost importance. Volatile nerve agent exposure, e.g. sarin, results in fast development of cholinergic crisis. Immediate clinical diagnosis can be confirmed on-site by assessment of acetylcholinesterase activity. Treatment with autoinjectors that are filled with 2mg atropine and an oxime (at present obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve agents. A more aggressive atropinisation has to be considered and more effective oximes (if possible with a broad spectrum or a combination of different oximes) as well as alternative strategies to cope with high acetylcholine levels at synaptic sites should be developed. A further gap exists for the treatment of patients with sustained cholinergic crisis that has to be expected after exposure to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial ventilation can be reduced with an oxime therapy that is optimized by using the cholinesterase status for guidance or by measures (e.g. scavengers) that are able to reduce the poison load substantially in the patients. For sulfur mustard poisoning no specific antidote is available until now. Symptomatic measures as used for treatment of burns are recommended together with surgical or laser debridement. Thus, huge amounts of resources are expected to be consumed as wound healing is impaired. Possible depots of sulfur mustard in tissues may aggravate the situation. More basic knowledge is necessary to improve substantially therapeutic options. The use of stem cells may provide a new and promising option. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Trimethylsilyl speciations of cathine, cathinone and norephedrine followed by gas chromatography mass spectrometry: Direct sample preparation and analysis of khatamines.

PubMed

Molnár, Borbála; Fodor, Blanka; Boldizsár, Imre; Molnár-Perl, Ibolya

2016-04-01

A literature criticism is given on methods using currently gas chromatography mass spectrometry (GC/MS) to determine cathine (CAT), cathinone (CTN) and norephedrine (NE), jointly khatamines. In this study, khatamines' oximation, trimethylsilylation and mass fragmentation properties-applying N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA), its trimethyliodosilane (TMIS) catalyst containing version (MSTFA(TMIS)), N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and hexamethyldisilazane (HMDS)-was highlighted, at first. Derivatization, mass fragmentation and quantitation related, optimized model investigations have been carried out as a function of the reaction times and conditions. Special emphasis was put (i) on the stability of the primarily formed (CAT-2TMS, NE-2TMS, CTN-TMS(TMS-oximes)1,2), then transformed, fully derived (CAT-3TMS, NE-3MTS, CTN-2TMS(TMS-oximes)1,2) species, and, (ii) on the proportionally formed stable products, suitable to selective quantitation of all three natural amines, simultaneously. Results, as novelty to the field confirmed that (i) TMIS catalyzed trimethylsilyation triggers to form fully derivatized species unfortunately, in part only; while, (ii) khatamines' simultaneous quantitation needs to be carried out in a two steps derivatization process consisting of oximation (1st step, hydroxylamine in pyridine) and trimethylsilylation (2nd step, MSTFA), to the CAT-2TMS, NE-2TMS, CTN-TMS(TMS-oximes)1,2. These species were characterized with their retention, mass fragmentation and analytical performance properties, in model solutions and in the presence of plant tissues, as well: R(2), limit of quantitation (LOQ) data, expressed in pg/1μL injection basis, proved to be 62.5pg (CAT), 20pg (NE) and 62.5pg (CTN), respectively. The practical utility of proposal was enormously enhanced by the novel, direct sample preparation method. In this process, the freshly harvested, freeze-dried, then pulverized leaves of Catha edulis FORKS were directly derivatized, in the presence of the matrix. Reproducibility (in average 2.07 RSD% varying between 0.15 and 5.5 RSD%), linearity (0.9990-0.9994) and recovery (95.7-99.1%) values of the new sample preparation protocol was confirmed by the standard addition method for CAT, NE and CTN equally. From plant leaf, 0.061w/w% CAT and 0.014w/w% NE contents were obtained. In this tissue CTN was not found. Very likely attributable to the unfavorable climate for the plant: grown in Hungary of temperate zone and naturalized in the tropical Africa. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of reversible interconversion in comprehensive two-dimensional gas chromatography using enantioselective columns in first and second dimensions.

PubMed

Kröger, Sabrina; Wong, Yong Foo; Chin, Sung-Tong; Grant, Jacob; Lupton, David; Marriott, Philip J

2015-07-24

The reversible molecular interconversion behaviour of a synthesised oxime (2-phenylpropanaldehyde oxime; (C6H5)CH(CH3)CHN(OH)) was investigated by both, single dimensional gas chromatography (1D GC) and comprehensive two-dimensional gas chromatography (GC×GC). Previous studies on small molecular weight oximes were extended to this larger aromatic oxime (molar mass 149.19gmol(-1)) with interest in the extent of interconversion, enantioselective resolution, and retention time. On a polyethylene glycol (PEG; wax-type) column, a characteristic interconversion zone between two antipodes of E and Z isomers was formed by molecules which have undergone isomerisation on the column (E⇌Z). The extent of interconversion was investigated by varying chromatographic conditions (oven temperature and carrier flow rate) to understand the nature of the behaviour observed. The extent of interconversion was negligible in both enantioselective and methyl-phenylpolysiloxane phase-columns, correlating with the low polarity of the stationary phase. In order to obtain isomerisation along with enantio-resolution, a wax-type and an enantioselective column were coupled in either enantioselective-wax or wax-enantioselective order. The most appropriate column arrangement was selected for study by using a GC×GC experiment with either a wax-phase or phenyl-methylpolysiloxane phase as (2)D column. In addition to evaluation of these fast elution columns, a long narrow-bore enantioselective column (10m) was introduced as (2)D, providing an enantioselective-PEG (coupled-column ensemble: (1)D1+(1)D2)×enantioselective ((2)D) column combination. In this instance, the (1)D1 enantioselective column provides enantiomeric separation of the corresponding enantiomers ((R) and (S)) of (E)- and (Z)-2-phenylpropanaldehyde oxime, followed by E/Z isomerisation in the coupled (1)D2 PEG (reactor) column. The resulting chromatographic interconversion region was modulated and separated into either E/Z isomers (achiral (2)D column) or into the respective (R) and (S) enantiomers of the E/Z isomers when using a (2)D enantioselective column. With this arrangement, the isomers underneath the broad interconversion plateau in 1D elution profiles, including the enantiomers, could be resolved, illuminating salient features and understanding of the molecular reversible process of the interconverting molecules during the chromatographic elution. The two-dimensional patterns (contour plots), resulting from the combination of interconversion process and chiral separation, are discussed phenomenologically. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis and Modification of Carboxylated Polyphenylenes and Phenylated Polyimides

DTIC Science & Technology

1976-03-01

corresponding grignard reagent , which was allowed to react with DMF19 to provide the benzalde- hyde 50. This aldehyde, however, failed to undergo a benzoin...bromophenylethynyl )-trimethyl- silane in 100 ml THF was refluxed 2 hr with 1.6 g (0.066 g atm) of magnesium to form the Grignard reagent . To the...toluene (Table 2). The crown other reagent , however, could not be completely removed from the resulting ionomer. Treatment of the carboxylated

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters.

PubMed

Uno, Takuya; Kobayashi, Yusuke; Takemoto, Yoshiji

2012-01-01

An efficient catalytic synthesis of α-amino-β-keto esters has been newly developed. Cross-coupling of various aldehydes with α-imino ester, catalyzed by N-heterocyclic carbene, leads chemoselectively to α-amino-β-keto esters in moderate to good yields with high atom efficiency. The reaction mechanism is discussed, and it is proposed that the α-amino-β-keto esters are formed under thermodynamic control.

Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates

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

Katz, Francine S.; Pecic, Stevan; Tran, Timothy H.

Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups—Mannich phenols and general bases—that are capable of reactivating OPC-inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data,more » significantly broaden the available approaches for reactivation of AChE.« less

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

PubMed Central

Rao, V Mohana

2012-01-01

Summary The titled approaches were effected with various 2-substituted benzoylacetic acid oximes 3 (Beckmann) and 2-substituted malonamic acids 9 (Hofmann), their carboxyl groups being masked as a 2,4,10-trioxaadamantane unit (an orthoacetate). The oxime mesylates have been rearranged with basic Al2O3 in refluxing CHCl3, and the malonamic acids with phenyliodoso acetate and KOH/MeOH. Both routes are characterized by excellent overall yields. Structure confirmation of final products was conducted with X-ray diffraction in selected cases. The final N-benzoyl and N-(methoxycarbonyl) products are α-amino acids with both carboxyl and amino protection; hence, they are of great interest in peptide synthesis. PMID:23019476

Pathogenesis and Treatment of Cerebral Air Embolism and Associated Disorders.

DTIC Science & Technology

1984-04-01

blades) 12. 7.0, 8.0 and 9.0-mm endotracheal tubes 13. Endotracheal tube stylet 14. Esophageal obturator airway 15. Tracheal suction catheters (14F) 17 r...16. Nasogastric suction tube and Tumee syringe 17. Tincture of Benzoin 18. 2-in waterproof tape 19. Precordial stethoscope 20. Esophageal stethoscope...be justified. If an endotracheal tube cannot be passed, an esophageal obturator airway may be useful. If such an airway Is used, the newer models

On the organocatalytic activity of N-heterocyclic carbenes: role of sulfur in thiamine.

PubMed

Hollóczki, Oldamur; Kelemen, Zsolt; Nyulászi, László

2012-07-20

The reaction energy profiles of the benzoin condensation from three aldehydes catalyzed by imidazol-2-ylidene, triazol-3-ylidene, and thiazol-2-ylidene have been investigated computationally. The barriers for all steps of all investigated reactions have been found to be low enough to indicate the viability of the mechanism proposed by Breslow in the 1950s. The most remarkable difference in the catalytic cycles has been the increased stability of the Breslow intermediate in case of thiazol-2-ylidene (by ca. 10 kcal/mol) compared to the other two carbenes, which results in lower energy for the coupling of the second aldehyde molecule, thus, increasing the reversibility of the reaction. Since the analogous transketolase reaction, being involved in the carbohydrate metabolism of many organisms, requires an initial decoupling-a reverse benzoin condensation-this difference provides a reasonable explanation for the presence of a thiazolium ring in thiamine instead of the otherwise generally more available imidazole derivatives. The "resting intermediate" found by Berkessel and co-workers for a triazole-based catalyst was found more stable than the Breslow intermediate for all of the systems investigated. The (gas phase) proton affinities of several carbenes were compared, the relative trends being in agreement with the available (in aqueous solution) data. The hydrolytic ring-opening reaction of the thiazole-based carbene was shown to be different from that of imidazole-2-ylidenes.

Synthesis of well-defined bisbenzoin end-functionalized poly(ε-caprolactone) macrophotoinitiator by combination of ROP and click chemistry and its use in the synthesis of star copolymers by photoinduced free radical promoted cationic polymerization

PubMed Central

Uyar, Zafer; Degirmenci, Mustafa; Genli, Nasrettin; Yilmaz, Ayse

2017-01-01

Abstract A new well-defined bisbenzoin group end-functionalized poly(ε-caprolactone) macrophotoinitiator (PCL-(PI)2) was synthesized by combination of ring opening polymerization (ROP) and click chemistry. The ROP of ε-CL monomer in bulk at 110 °C, by means of a hydroxyl functional initiator namely, 3-cyclohexene-1-methanol in conjunction with stannous-2-ethylhexanoate, (Sn(Oct)2), yielded a well-defined PCL with a cyclohexene end-chain group (PCL-CH). The bromination and subsequent azidation of the cyclohexene end-chain group gave bisazido functionalized poly(ε-caprolactone) (PCL-(N3)2). Separately, an acetylene functionalized benzoin photoinitiator (PI-alkyne) was synthesized by using benzoin and propargyl bromide. Then the click reaction between PCL-(N3)2 and PI-alkyne was performed by Cu(I) catalysis. The spectroscopic studies revealed that poly(ε-caprolactone) with bisbenzoin photoactive functional group at the chain end (PCL-(PI)2) with controlled chain length and low-polydispersity was obtained. This PCL-(PI)2 macrophotoinitiator was used as a precursor in photoinduced free radical promoted cationic polymerization to synthesize an AB2-type miktoarm star copolymer consisting of poly(ε-caprolactone) (PCL, as A block) and poly(cyclohexene oxide) (PCHO, as B block), namely PCL(PCHO)2. PMID:29491778

A new agent for derivatizing carbonyl species used to investigate limonene ozonolysis

NASA Astrophysics Data System (ADS)

Wells, J. R.; Ham, Jason E.

2014-12-01

A new method for derivatizing carbonyl compounds is presented. The conversion of a series of dicarbonyls to oximes in aqueous solution and from gas-phase sampling was achieved using O-tert-butylhydroxylamine hydrochloride (TBOX). Some advantages of using this derivatization agent include: aqueous reactions, lower molecular weight oximes, and shortened oxime-formation reaction time. Additionally, the TBOX derivatization technique was used to investigate the carbonyl reaction products from limonene ozonolysis. With ozone (O3) as the limiting reagent, four carbonyl compounds were detected: 7-hydroxy-6-oxo-3-(prop-1-en-2-yl)heptanal; 3-Isopropenyl-6-oxoheptanal (IPOH), 3-acetyl-6-oxoheptanal (3A6O) and one carbonyl of unknown structure. Using cyclohexane as a hydroxyl (OHrad) radical scavenger, the relative yields (peak area) of the unknown carbonyl, IPOH, and 3A6O were reduced indicating the influence secondary OH radicals have on limonene ozonolysis products. The relative yield of the hydroxy-dicarbonyl based on the chromatogram was unchanged suggesting it is only made by the limonene + O3 reaction. The detection of 3A6O using TBOX highlights the advantages of a smaller molecular weight derivatization agent for the detection of multi-carbonyl compounds. The use of TBOX derivatization if combined with other derivatization agents may address a recurring need to simply and accurately detect multi-functional oxygenated species in air.

21 CFR 520.1443 - Milbemycin oxime and lufenuron.

Code of Federal Regulations, 2014 CFR

2014-04-01

... prevention and control of flea populations, for control of adult Ancylostoma caninum (hookworm), and for removal and control of adult Toxocara canis, Toxascaris leonina (roundworm), and Trichuris vulpis...

21 CFR 520.1443 - Milbemycin oxime and lufenuron.

Code of Federal Regulations, 2013 CFR

2013-04-01

... prevention and control of flea populations, for control of adult Ancylostoma caninum (hookworm), and for removal and control of adult Toxocara canis, Toxascaris leonina (roundworm), and Trichuris vulpis...

Functionalized SBA-15 supported nickel (II)-oxime-imine catalysts for liquid phase oxidation of olefins under solvent-free conditions

NASA Astrophysics Data System (ADS)

Paul, Luna; Banerjee, Biplab; Bhaumik, Asim; Ali, Mahammad

2016-05-01

A new oxime-imine functionalized highly ordered mesoporous SBA-15 (SBA-15-NH2-DAMO) has been synthesized via post-synthesis functionalization of SBA-15 with 3-aminopropyl-triethoxysilane followed by the Schiff base condensation with diacetylmonooxime, which was further reacted with Ni(ClO4)2 to yield the functionalized nickel catalyst SBA-15-NH2-DAMO-Ni. All the synthesized materials were thoroughly characterized using different characterization techniques. It was found that SBA-15-NH2-DAMO-Ni catalyzes the one-pot oxidation of olefins like styrene, cyclohexene, cyclooctene, 1-hexene and 1-octene to the corresponding benzaldehyde, cyclohexene-1-ol and cyclooctene-oxide, respectively under solvent-free conditions by using tert-butylhydroperoxide as oxidant.

Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition.

PubMed

Furnival, Rachel C; Saruengkhanphasit, Rungroj; Holberry, Heather E; Shewring, Jonathan R; Guerrand, Hélène D S; Adams, Harry; Coldham, Iain

2016-11-22

Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine.

Milbemycin oxime in a new formulation, combined with praziquantel, does not reduce the efficacy of praziquantel against Echinococcus multilocularis in cats.

PubMed

Jenkins, D J; Romig, T

2003-12-01

Twenty European domestic cats were each infected with 15,000 protoscoleces of Echinococcus multilocularis extracted from metacestodes grown in experimentally infected common voles (Microtus arvalis). Sixteen days after infection, ten cats were treated with a broad-spectrum anthelmintic and acaricide comprising praziquantel and milbemycin oxime. Five days later treated and untreated cats were euthanized and the intestine examined for E. multilocularis. Five of ten untreated cats were infected with E. multilocularis with worm burdens ranging from 235 to 1920 worms per cat. No E. multilocularis were recovered from any of the treated cats. This study has demonstrated that this new combination broad spectrum anthelmintic and acaricide for cats is highly efficacious against E. multilocularis and the relevance of this is discussed.

Increased targeting of adenine-rich sequences by (2-amino-2-methyl-3-butanone oxime)dichloroplatinum(II) and investigations into its low cytotoxicity.

PubMed

Hambley, T W; Ling, E C; O'Mara, S; McKeage, M J; Russell, P J

2000-12-01

Using assays based on the inhibition of restriction enzyme cleavage of plasmid and synthetic DNA, the complex (2-amino-2-methyl-3-butanone oxime)dichloroplatinum(II), [PtCl2(ambo)], has been shown to have an increased tendency for binding to adenine-rich sequences when compared to cis[PtCl2(NH3)2] (cisplatin). [PtCl2(ambo)] was found to form substantially fewer interstrand adducts than does cisplatin. The in vitro cytotoxicity of [PtCl2(ambo)] against a human bladder cancer cell line was determined and found to be more than two orders of magnitude lower than that of cisplatin, yet it was also found to be equally effective at passing into cells and binding to isolated DNA.

Design, Synthesis and Evaluation of Novel Isoxazolines/Oxime Sulfonates of 2‧(2‧,6‧)-(Di)Chloropodophyllotoxins as Insecticidal Agents

NASA Astrophysics Data System (ADS)

Yu, Mingqiao; Liu, Guangci; Zhang, Yuanyuan; Feng, Tao; Xu, Ming; Xu, Hui

2016-09-01

A series of 2‧(2‧,6‧)-(di)halogeno-isoxazolopodophyllic acids-based esters, and oxime sulfonates of 2‧(2‧,6‧)-(di)halogenopodophyllones were prepared by structural modifications of podophyllotoxin as insecticidal agents against Mythimna separata Walker. It was found that when 2‧(2‧,6‧)-(di)halogenopodophyllones or 2‧(2‧,6‧)-(di)chloropicropodophyllones reacted with hydroxylamine hydrochloride, the desired products were related with the configuration of their lactones. Three key single-crystal structures of Ie, IIe and IIIb were determined by X-ray diffraction. Especially compounds IIc and Vc showed the highest insecticidal activity. Moreover, some interesting results of structure-insecticidal activity relationships of tested compounds were also observed.

21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... prevention and control of flea populations, for control of adult Ancylostoma caninum (hookworm), and for removal and control of adult Toxocara canis, Toxascaris leonina (roundworm), and Trichuris vulpis...

21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... prevention and control of flea populations, for control of adult Ancylostoma caninum (hookworm), and for removal and control of adult Toxocara canis, Toxascaris leonina (roundworm), and Trichuris vulpis...

Electronic structure and properties of unsubstituted rhodamine in different electron states

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

Artyukhov, V.Ya.

1988-04-01

An analysis is given of the electron density distribution, dipole moment variation, and proton acceptor properties of unsubstituted rhodamine molecules in different electron states. It is shown that the electron density redistribution between the pyronine and benzoin parts of rhodamine may be large and strongly affect the molecular properties. In one of the electron transitions (S/sub 4/) producing the third absorption band the proton acceptor power markedly increases, giving rise to a protonated form under suitable conditions.

Chemically Amplified Bilevel Resist Based on Condensation of Siloxanes

NASA Astrophysics Data System (ADS)

Sakata, Miwa; Ito, Toshio; Yamashita, Yoshio

1991-11-01

This paper deals with a negative bilevel resist which is based on the acid-catalyzed condensation reaction of poly(siloxane)s. The resist systems consist of photoacid generators and poly(siloxane). Ph3S+OTf- reveals an efficient activity for silanol condensation and the system has a high sensitivity of 0.31 mJ/cm2. Tetrafunctional silane plays the role of crosslinker in this system. Sensitivity improvement of low-sensitivity systems such as benzoin p-toluenesulfonate/poly(siloxane) can be achieved by this method.

Silyl Ketene Imines: Highly Versatile Nucleophiles for Catalytic, Asymmetric Synthesis

PubMed Central

Denmark, Scott E.; Wilson, Tyler W.

2012-01-01

This Minireview provides an overview on the development of silyl ketene imines and their recent applications in catalytic, enantioselective reactions. The unique structure of the ketene imine allows a diverse range of reactivity patterns and provides solutions to existing challenges in the enantioselective construction of quaternary stereogenic carbon centers and cross-benzoin adducts. A variety of reactions for which silyl ketene imines have been applied are presented with an overall goal of inspiring new uses for these underutilized nucleophiles. PMID:22968901

Electronic structure and properties of unsubstituted rhodamine in different electron states

NASA Astrophysics Data System (ADS)

Artyukhov, V. Ya.

1987-10-01

An analysis is given of the electron density distribution, dipole moment variation, and proton acceptor properties of unsubstituted rhodamine molecules in different electron states. It is shown that the electron density redistribution between the pyronine and benzoin parts of rhodamine may be large and strongly affect the molecular properties. In one of the electron transitions (S4) producing the third absorption band the proton acceptor power markedly increases, giving rise to a protonated form under suitable conditions.

Novel pyrrolinones as N-methyl-D-aspartate receptor antagonists.

PubMed

Poschenrieder, Hermann; Stachel, Hans-Dietrich; Höfner, Georg; Mayer, Peter

2005-04-01

A series of oximes, deriving from 2-arylidene-pyrroline-3,4-diones (7, 8, 22, 23) has been prepared. The presence of tautomers in their solutions has been established by spectroscopic means. The compounds reacted with diazomethane chiefly by N-methylation forming nitrones (10, 11). The analogously prepared 2-arylidene-4-nitropyrrolin-3-ones (12, 13, 24, 25), formally derived from nitrotetramic acids, yielded nitronic acid esters (14, 15, 26) upon reaction with diazomethane. The structures were elucidated by spectral evidence and-in the case of compounds 10 and 20b-by X-ray diffraction analysis. The binding affinity of some of the new compounds toward the N-methyl-d-aspartate (NMDA) (glycine site) receptor has been measured thus providing the basis for further structure-activity relationship studies. Oxime 8b showed the highest binding potency (Ki= 9.2 microM).

Carbamate and Pyrethroid Resistance in the Akron Strain of Anopheles gambiae

PubMed Central

Mutunga, James M.; Anderson, Troy D.; Craft, Derek T.; Gross, Aaron D.; Swale, Daniel R.; Tong, Fan; Wong, Dawn M.; Carlier, Paul R.; Bloomquist, Jeffrey R.

2015-01-01

Insecticide resistance in the malaria vector, Anopheles gambiae is a serious problem, epitomized by the multi-resistant Akron strain, originally isolated in the country of Benin. Here we report resistance in this strain to pyrethroids and DDT (13-fold to 35-fold compared to the susceptible G3 strain), but surprisingly little resistance to etofenprox, a compound sometimes described as a “pseudo-pyrethroid.” There was also strong resistance to topically-applied commercial carbamates (45-fold to 81-fold), except for the oximes aldicarb and methomyl. Biochemical assays showed enhanced cytochrome P450 monooxygenase and carboxylesterase activity, but not that of glutathione-S-transferase. A series of substituted α,α,α,-trifluoroacetophenone oxime methylcarbamates were evaluated for enzyme inhibition potency and toxicity against G3 and Akron mosquitoes. The compound bearing an unsubstituted phenyl ring showed the greatest toxicity to mosquitoes of both strains. Low cross resistance in Akron was retained by all analogs in the series. Kinetic analysis of acetylcholinesterase activity and its inhibition by insecticides in the G3 strain showed inactivation rate constants greater than that of propoxur, and against Akron enzyme inactivation rate constants similar to that of aldicarb. However, inactivation rate constants against recombinant human AChE were essentially identical to that of the G3 strain. Thus, the acetophenone oxime carbamates described here, though potent insecticides that control resistant Akron mosquitoes, require further structural modification to attain acceptable selectivity and human safety. PMID:26047119

Design, evaluation and structure-activity relationship studies of the AChE reactivators against organophosphorus pesticides.

PubMed

Musilek, Kamil; Dolezal, Martin; Gunn-Moore, Frank; Kuca, Kamil

2011-07-01

Organophosphate pesticides (OPPs; e.g. chlorpyrifos, diazinon, paraoxon) are a wide and heterogeneous group of organophosphorus compounds. Their biological activity of inhibiting acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) ranks them as life endangering agents. The necessary treatment after OPP exposure involves the use of parasympatolytics (e.g. atropine), oxime reactivators (e.g. obidoxime), and anticonvulsive drugs (e.g. diazepam). Therefore, the reactivators of AChE are essential compounds in the treatment of OPP intoxications. Commercial AChE reactivators (e.g. pralidoxime, HI-6, obidoxime, trimedoxime, methoxime) were originally developed for other members of the organophosphate family, such as nerve agents (e.g. sarin, soman, tabun, VX). Pralidoxime, HI-6, and methoxime were found to be weak reactivators of OPP-inhibited AChE. Obidoxime and trimedoxime showed satisfactory reactivation against various OPPs with minor toxicity issues. During the last two decades, the treatment of OPP exposure has become more widely discussed because of growing agricultural production, industrialization, and harmful social issues (e.g. suicides). In this review is the summarized design, evaluation, and structure-activity relationship studies of recently produced AChE reactivators. Since pralidoxime, over 300 oximes have been produced or tested against OPP poisoning, and several novel compounds show very promising abilities as comparable (or higher) to commercial oximes. Some of these are highlighted for their further testing of OPP exposure and, additionally, the main structure-activity relationship of AChE reactivators against OPP is discussed. © 2009 Wiley Periodicals, Inc.

Physicochemical characterization and toxicity of decursin and their derivatives from Angelica gigas.

PubMed

Mahat, Bimit; Chae, Jung-Woo; Baek, In-Hwan; Song, Gyu-Yong; Song, Jin-Sook; Cho, Seong-Kwon; Kwon, Kwang-Il

2012-01-01

Angelica gigas NAKAI is used to treat dysmenorrhea, amenorrhea, menopause, abdominal pain, injuries, migraine, and arthritis. The present study provided a physicochemical and toxicological characterization of compounds in A. gigas NAKAI (decursin, decursinol angelate, diketone decursin, ether decursin, epoxide decursin and oxim decursin). Diketone decursin (173.16 μg/mL) and epoxide decursin (122.12 μg/mL) exhibited >100 μg/mL kinetic solubility after applying nephelometry, suggesting a highly soluble compound. The Student’s t-test revealed significant differences in the pKa ranges of the compounds by automatic titration from capillary electrophoresis (p<0.05). Diketone decursin, epoxide decursin and oxim decursin might be formulated into an oral dosage form (log P: 0-3) by an automatic titration analysis. A parallel artificial membrane permeability assay demonstrated permeability coefficients of <10 x 10⁻⁶ cm/s for all of the compounds, suggesting poor permeability. Ether decursin exhibited a toxic effect after being applied to mouse (NIH 3T3, EC₅₀: 57.9 μM) and human (HT-29, EC₅₀: 36.1 μM; Hep-G2, EC₅₀: 4.92 μM) cells. Additionally, epoxide and oxim decursin were toxic through acute oral toxicity (four and three deaths of Institute of Cancer Research (ICR) mice) and mutation toxicity testing by applying Salmonella typhimurium cells with and without S9. Although diketone decursin exhibited less permeability, it is potentially valuable pharmacological compound that should be investigated.

A Fluorescent Hypochlorite Probe Built on 1,10-Phenanthroline Scaffold and its Ion Recognition Features.

PubMed

Algi, Melek Pamuk

2016-03-01

In this study, the synthesis of 7-((Hydroxyimino)methyl)-1,10-phenanthroline-4-carbaldehyde oxime (1) in two steps starting from 4,7-dimethyl-1,10-phenanthroline (2) is reported. It is found that compound 1 can be used as a fluorogenic probe for the detection of hypochlorite ion in aqueous solution. NMR and mass spectral analysis indicate that probe 1 undergoes a chemical transformation through its oxime units upon treatment with hypochlorite, which results in a remarkable enhancement of the emission intensity. Also, metal ion recognition properties of probe 1 is investigated. It is noted that compound 1 is responsive to Zn(2+), Cd(2+), Ni(2+) and Cu(2+) metal ions, which reduced the emission intensity under identical conditions. Graphical Abstract The design, synthesis and properties of a new fluorescent hypochlorite probe is described. It is found that probe 1 immediately undergoes an oxidation reaction with NaClO through its oxime units in 0.1 M Na2CO3-NaHCO3 buffer containing DMF (pH = 9.0, 30:1 v/v) at room temperature, which resulted in a remarkable enhancement of the emission intensity. It is noteworthy that this novel probe 1 is highly selective to hypochlorite ion when compared to some other ROS and anions. On the other hand, probe 1 also induces turn-off fluorogenic responses to metal ions such as Zn(2+), Cd(2+), Ni(2+) and Cu(2+) ions under identical conditions.

Bioactive Potential of 3D-Printed Oleo-Gum-Resin Disks: B. papyrifera, C. myrrha, and S. benzoin Loading Nanooxides—TiO2, P25, Cu2O, and MoO3

PubMed Central

Tebcherani, Sergio Mazurek; Kubaski, Evaldo Toniolo; de Almeida Vieira, Rogério

2017-01-01

This experimental study investigates the bioactive potential of filaments produced via hot melt extrusion (HME) and intended for fused deposition modeling (FDM) 3D printing purposes. The oleo-gum-resins from benzoin, myrrha, and olibanum in pure state and also charged with 10% of metal oxide nanoparticles, TiO2, P25, Cu2O, and MoO3, were characterized by ultraviolet-visible (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray microanalysis (EDXMA), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Disks were 3D-printed into model geometries (10 × 5 mm) and the disk-diffusion methodology was used for the evaluation of antimicrobial and antifungal activity of materials in study against the clinical isolates: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. Due to their intrinsic properties, disks containing resins in pure state mostly prevent surface-associated growth; meanwhile, disks loaded with 10% oxides prevent planktonic growth of microorganisms in the susceptibility assay. The microscopy analysis showed that part of nanoparticles was encapsulated by the biopolymeric matrix of resins, in most cases remaining disorderly dispersed over the surface of resins. Thermal analysis shows that plant resins have peculiar characteristics, with a thermal behavior similar to commercial available semicrystalline polymers, although their structure consists of a mix of organic compounds. PMID:28811751

Heterofunctional Magnetic Metal-Chelate-Epoxy Supports for the Purification and Covalent Immobilization of Benzoylformate Decarboxylase From Pseudomonas Putida and Its Carboligation Reactivity.

PubMed

Tural, Servet; Tural, Bilsen; Demir, Ayhan S

2015-09-01

In this study, the combined use of the selectivity of metal chelate affinity chromatography with the capacity of epoxy supports to immobilize poly-His-tagged recombinant benzoylformate decarboxylase from Pseudomonas putida (BFD, E.C. 4.1.1.7) via covalent attachment is shown. This was achieved by designing tailor-made magnetic chelate-epoxy supports. In order to selectively adsorb and then covalently immobilize the poly-His-tagged BFD, the epoxy groups (300 µmol epoxy groups/g support) and a very small density of Co(2+)-chelate groups (38 µmol Co(2+)/g support) was introduced onto magnetic supports. That is, it was possible to accomplish, in a simple manner, the purification and covalent immobilization of a histidine-tagged recombinant BFD. The magnetically responsive biocatalyst was tested to catalyze the carboligation reactions. The benzoin condensation reactions were performed with this simple and convenient heterogeneous biocatalyst and were comparable to that of a free-enzyme-catalyzed reaction. The enantiomeric excess (ee) of (R)-benzoin was obtained at 99 ± 2% for the free enzyme and 96 ± 3% for the immobilized enzyme. To test the stability of the covalently immobilized enzyme, the immobilized enzyme was reused in five reaction cycles for the formation of chiral 2-hydroxypropiophenone (2-HPP) from benzaldehyde and acetaldehyde, and it retained 96% of its original activity after five reaction cycles. © 2015 Wiley Periodicals, Inc.

Achiral and Chiral Separations Using Micellar Electrokinetic Chromatography, Polyelectrolyte Multilayer Coatings, and Mixed Mode Separation Techniques with Molecular Micelles

PubMed Central

Luces, Candace A.; Warner, Isiah M.

2014-01-01

Mixed mode separation using a combination of micellar electrokinetic chromatography (MEKC) and polyelectrolyte multilayer (PEM) coatings is herein reported for the separation of achiral and chiral analytes. Many analytes are difficult to separate by MEKC and PEM coatings alone. Therefore, the implementation of a mixed mode separation provides several advantages for overcoming the limitations of these well-established methods. In this study, it was observed that achiral separations using MEKC and PEM coatings individually resulted in partial resolution of 8 very similar aryl ketones when the molecular micelle (sodium poly(N-undecanoyl-l-glycinate) (poly-SUG)) concentration was varied from 0.25% – 1.00% (w/v) and the bilayer number varied from 2 – 4. However, when mixed mode separation was introduced, baseline resolution was achieved for all 8 analytes. In the case of chiral separations, temazepam, aminoglutethimide, benzoin, benzoin methyl ether and coumachlor were separated using the three separation techniques. For chiral separations, the chiral molecular micelle, sodium poly(N-undecanoyl-l-leucylvalinate) (poly-l-SULV), was employed at concentrations of 0.25–1.50% (w/v) for both MEKC and PEM coatings. Overall, the results revealed partial separation with MEKC and PEM coatings individually. However, mixed mode separation enabled baseline separation of each chiral mixture. The separation of achiral and chiral compounds from different compound classes demonstrates the versatility of this mixed mode approach. PMID:20155738

Bioactive Potential of 3D-Printed Oleo-Gum-Resin Disks: B. papyrifera, C. myrrha, and S. benzoin Loading Nanooxides-TiO2, P25, Cu2O, and MoO3.

PubMed

Horst, Diogo José; Tebcherani, Sergio Mazurek; Kubaski, Evaldo Toniolo; de Almeida Vieira, Rogério

2017-01-01

This experimental study investigates the bioactive potential of filaments produced via hot melt extrusion (HME) and intended for fused deposition modeling (FDM) 3D printing purposes. The oleo-gum-resins from benzoin, myrrha, and olibanum in pure state and also charged with 10% of metal oxide nanoparticles, TiO 2 , P25, Cu 2 O, and MoO 3 , were characterized by ultraviolet-visible (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray microanalysis (EDXMA), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Disks were 3D-printed into model geometries (10 × 5 mm) and the disk-diffusion methodology was used for the evaluation of antimicrobial and antifungal activity of materials in study against the clinical isolates: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli , and Candida albicans . Due to their intrinsic properties, disks containing resins in pure state mostly prevent surface-associated growth; meanwhile, disks loaded with 10% oxides prevent planktonic growth of microorganisms in the susceptibility assay. The microscopy analysis showed that part of nanoparticles was encapsulated by the biopolymeric matrix of resins, in most cases remaining disorderly dispersed over the surface of resins. Thermal analysis shows that plant resins have peculiar characteristics, with a thermal behavior similar to commercial available semicrystalline polymers, although their structure consists of a mix of organic compounds.

21 CFR 520.1445 - Milbemycin oxime tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Administer once a month. First dose given within 1 month after first exposure to mosquitoes and continue regular use until at least 1 month after end of mosquito season. Federal law restricts this drug to use by...

On the Reaction of Carbonyl Diphosphonic Acid with Hydroxylamine and O-alkylhydroxylamines: Unexpected Degradation of P-C-P Bridge.

PubMed

Khomich, Olga A; Yanvarev, Dmitry V; Novikov, Roman A; Kornev, Alexey B; Puljulla, Elina; Vepsäläinen, Jouko; Khomutov, Alex R; Kochetkov, Sergey N

2017-06-23

Derivatives of methylenediphosphonic acid possess wide spectra of biological activities and are used in enzymology as research tools as well as in practical medicine. Carbonyl diphosphonic acid is a promising starting building block for synthesis of functionally substituted methylenediphosphonates. Investigation of the interaction of carbonyl diphosphonic acid with hydroxylamine clearly demonstrates that it is impossible to isolate oxime within the pH range 2-12, while only cyanophosphonic and phosphoric acids are the products of the fast proceeding Beckmann-like fragmentation. In the case of O -alkylhydroxylamines, corresponding alcohols are found in the reaction mixtures in addition to cyanophosphonic and phosphoric acids. Therefore, two residues of phosphonic acid being attached to a carbonyl group provide new properties to this carbonyl group, making its oximes very unstable. This principally differs carbonyl diphosphonic acid from structurally related phosphonoglyoxalic acid and other α-ketophosphonates.

Efficacy of fenbendazole and milbemycin oxime for treating baboons (Papio cynocephalus anubis) infected with Trichuris trichiura.

PubMed

Reichard, Mason V; Wolf, Roman F; Carey, David W; Garrett, Jennifer Jane; Briscoe, Heather A

2007-03-01

We evaluated the efficacy of fenbendazole (FBZ) and milbemycin oxime (MO) in the treatment of baboons (Papio cynocephalus anubis) with naturally acquired Trichuris trichiura infection by comparing fecal egg count reduction (FECR) tests. We assigned 7 baboons, each singly housed and confirmed infected with T. trichiura, to treatment groups of FBZ (n=3) or MO (n=3), or as a control (n=1). All (100%) baboons that received FBZ stopped shedding T. trichiura eggs within 6 d of treatment, and fecal egg counts remained negative at 65 d after treatment. Although the number of T. trichiura eggs shed per gram of feces from 2 (67%) baboons decreased significantly after the second treatment with MO, this regimen never totally eliminated eggs of T. trichiura. The results of our study indicate that FBZ was more effective for treating baboons with T. trichiura than was MO.

The role of the oximes HI-6 and HS-6 inside human acetylcholinesterase inhibited with nerve agents: a computational study.

PubMed

Cuya, Teobaldo; Gonçalves, Arlan da Silva; da Silva, Jorge Alberto Valle; Ramalho, Teodorico C; Kuca, Kamil; C C França, Tanos

2017-10-27

The oximes 4-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HI-6) and 3-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HS-6) are isomers differing from each other only by the position of the carbamoyl group on the pyridine ring. However, this slight difference was verified to be responsible for big differences in the percentual of reactivation of acetylcholinesterase (AChE) inhibited by the nerve agents tabun, sarin, cyclosarin, and VX. In order to try to find out the reason for this, a computational study involving molecular docking, molecular dynamics, and binding energies calculations, was performed on the binding modes of HI-6 and HS-6 on human AChE (HssAChE) inhibited by those nerve agents.

Probing Functional Heteromeric Chemokine Protein-Protein Interactions through Conformation-Assisted Oxime Ligation.

PubMed

Agten, Stijn M; Koenen, Rory R; Ippel, Hans; Eckardt, Veit; von Hundelshausen, Philipp; Mayo, Kevin H; Weber, Christian; Hackeng, Tilman M

2016-11-21

Protein-protein interactions (PPIs) govern most processes in living cells. Current drug development strategies are aimed at disrupting or stabilizing PPIs, which require a thorough understanding of PPI mechanisms. Examples of such PPIs are heteromeric chemokine interactions that are potentially involved in pathological disorders such as cancer, atherosclerosis, and HIV. It remains unclear whether this functional modulation is mediated by heterodimer formation or by the additive effects of mixed chemokines on their respective receptors. To address this issue, we report the synthesis of a covalent RANTES-PF4 heterodimer (termed OPRAH) by total chemical synthesis and oxime ligation, with an acceleration of the final ligation step driven by PPIs between RANTES and PF4. Compared to mixed separate chemokines, OPRAH exhibited increased biological activity, thus providing evidence that physical formation of the heterodimer indeed mediates enhanced function. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Probing Functional Heteromeric Chemokine Protein–Protein Interactions through Conformation‐Assisted Oxime Ligation

PubMed Central

Agten, Stijn M.; Koenen, Rory R.; Ippel, Hans; Eckardt, Veit; von Hundelshausen, Philipp; Mayo, Kevin H.; Weber, Christian

2016-01-01

Abstract Protein–protein interactions (PPIs) govern most processes in living cells. Current drug development strategies are aimed at disrupting or stabilizing PPIs, which require a thorough understanding of PPI mechanisms. Examples of such PPIs are heteromeric chemokine interactions that are potentially involved in pathological disorders such as cancer, atherosclerosis, and HIV. It remains unclear whether this functional modulation is mediated by heterodimer formation or by the additive effects of mixed chemokines on their respective receptors. To address this issue, we report the synthesis of a covalent RANTES‐PF4 heterodimer (termed OPRAH) by total chemical synthesis and oxime ligation, with an acceleration of the final ligation step driven by PPIs between RANTES and PF4. Compared to mixed separate chemokines, OPRAH exhibited increased biological activity, thus providing evidence that physical formation of the heterodimer indeed mediates enhanced function. PMID:27785869

Influence of the nature of the ligand on the structure and spectra of boron-containing iron(II) dioximates

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

Pol'shin, E.V.; Trachevskii, V.V.; Tyukhtenko, S.I.

1987-11-01

The Moessbauer (/sup 57/Fe) and NMR (/sup 1/H, /sup 13/C, /sup 11/B) spectra of the macrobicyclic dioximates FeD/sub 3/(BF)/sub 2/, where H/sub 2/D stands for glyoxime, methylglyoxime, 1,2-cyclohexanedione dioxime (Nioxime), furildioxime, and benzil dioxime, have been investigated. The values of the isomer shifts for these compounds range from 0.31 to 0.37 mm/sec relative to sodium nitroprusside, and the Raman scattering ranges from 0.6 to 0.9 for the aliphatic oximes and is equal to approx. 0.2 for the aromatic oximes. The changes in the Raman scattering have been related to the angle of distortion of the trigonal prism. The greatest changesmore » in the /sup 13/C and /sup 1/H NMR spectra are observed for the atoms of the substituents.« less

Organophosphorus poisoning (acute).

PubMed

2007-03-01

Acute organophosphorus poisoning occurs after dermal, respiratory, or oral exposure to either low-volatility pesticides (e.g. chlorpyrifos, dimethoate) or high-volatility nerve gases (e.g. sarin, tabun). Most cases occur in resource-poor countries as a result of occupational or deliberate exposure to organophosphorus pesticides. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute organophosphorus poisoning? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: activated charcoal, alpha2 adrenergic receptor agonists, atropine, benzodiazepines, butyrylcholinesterase replacement therapy, cathartics, extracorporeal clearance, gastric lavage, glycopyrronium bromide, ipecacuanha, magnesium sulphate, milk or other home remedies, N-methyl-D-aspartate receptor antagonists, organophosphorus hydrolases, oximes, sodium bicarbonate, washing the poisoned person and removing contaminated clothing.

Organophosphorus poisoning (acute).

PubMed

Blain, Peter G

2011-05-17

Acetylcholinesterase inhibition by organophosphorus pesticides or organophosphate nerve agents can cause acute parasympathetic system dysfunction, muscle weakness, seizures, coma, and respiratory failure. Prognosis depends on the dose and relative toxicity of the specific compound, as well as pharmacokinetic factors. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute organophosphorus poisoning? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: activated charcoal (single or multiple doses), alpha(2) adrenergic receptor agonists, atropine, benzodiazepines, butyrylcholinesterase replacement therapy, cathartics, extracorporeal clearance, gastric lavage, glycopyrronium bromide (glycopyrrolate), ipecacuanha (ipecac), magnesium sulphate, milk or other home remedy immediately after ingestion, N-methyl-D-aspartate receptor antagonists, organophosphorus hydrolases, oximes, removing contaminated clothes and washing the poisoned person, and sodium bicarbonate.

Investigation of chemical and spin dynamics in micellized radical pairs by time-resolved stimulated nuclear polarization. Theory and experiment

NASA Astrophysics Data System (ADS)

Parnachev, A. P.; Bagryanskaya, E. G.; Tarasov, V. F.; Lukzen, N. N.; Sagdeev, R. Z.

1995-10-01

A numerical solution of the stochastic Liouville equation for a microreactor model is applied to the theoretical treatment of time-resolved stimulated nuclear polarization data, obtained during the investigation of micellized radical pairs, conducted in two different modes. Escape rate constants and relaxation parameters of radical pairs formed in the photolysis of methyldeoxybenzoin and benzoin in alkyl sulfate micelles of different sizes have been obtained. The conditions of the S-T 0 quantum oscillations in SNP kinetics have been determined.

The role of partitioning of reagents in grafting and curing reactions initiated by ionizing radiation and UV

NASA Astrophysics Data System (ADS)

Chaplin, R. P.; Dworjanyn, P. A.; Gamage, N. J. W.; Garnett, J. L.; Jankiewicz, S. V.; Khan, M. A.; Sangster, D. F.

1996-03-01

Experimental evidence involving monomer absorption studies using tritiated styrene is shown to support the proposal that additives such as mineral acids and certain inorganic salts when dissolved in the monomer solution enhance radiation grafting yields by a mechanism involving partitioning of reagents. Photoinitiators such as benzoin ethyl ether and its methyl analogue are reported as new additives for grafting of styrene in methanol to cellulose and polypropylene initiated by ionizing radiation. The partitioning concept is shown to be relevant in analogous UV grafting and curing processes.

Rate and Equilibrium Constants for the Addition of N-Heterocyclic Carbenes into Benzaldehydes: A Remarkable 2-Substituent Effect**

PubMed Central

Collett, Christopher J; Massey, Richard S; Taylor, James E; Maguire, Oliver R; O'Donoghue, AnnMarie C; Smith, Andrew D

2015-01-01

Rate and equilibrium constants for the reaction between N-aryl triazolium N-heterocyclic carbene (NHC) precatalysts and substituted benzaldehyde derivatives to form 3-(hydroxybenzyl)azolium adducts under both catalytic and stoichiometric conditions have been measured. Kinetic analysis and reaction profile fitting of both the forward and reverse reactions, plus onwards reaction to the Breslow intermediate, demonstrate the remarkable effect of the benzaldehyde 2-substituent in these reactions and provide insight into the chemoselectivity of cross-benzoin reactions. PMID:25908493

Rate and Equilibrium Constants for the Addition of N‐Heterocyclic Carbenes into Benzaldehydes: A Remarkable 2‐Substituent Effect†

PubMed Central

Collett, Christopher J.; Massey, Richard S.; Taylor, James E.; Maguire, Oliver R.

2015-01-01

Abstract Rate and equilibrium constants for the reaction between N‐aryl triazolium N‐heterocyclic carbene (NHC) precatalysts and substituted benzaldehyde derivatives to form 3‐(hydroxybenzyl)azolium adducts under both catalytic and stoichiometric conditions have been measured. Kinetic analysis and reaction profile fitting of both the forward and reverse reactions, plus onwards reaction to the Breslow intermediate, demonstrate the remarkable effect of the benzaldehyde 2‐substituent in these reactions and provide insight into the chemoselectivity of cross‐benzoin reactions. PMID:27478264

Determination of glycoside hydrolase specificities during hydrolysis of plant cell walls using glycome profiling

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

Walker, Johnnie A.; Pattathil, Sivakumar; Bergeman, Lai F.

Glycoside hydrolases (GHs) are enzymes that hydrolyze polysaccharides into simple sugars. To better understand the specificity of enzyme hydrolysis within the complex matrix of polysaccharides found in the plant cell wall, we studied the reactions of individual enzymes using glycome profiling, where a comprehensive collection of cell wall glycan-directed monoclonal antibodies are used to detect polysaccharide epitopes remaining in the walls after enzyme treatment and quantitative nanostructure initiator mass spectrometry (oxime-NIMS) to determine soluble sugar products of their reactions. Single, purified enzymes from the GH5_4, GH10, and GH11 families of glycoside hydrolases hydrolyzed hemicelluloses as evidenced by the loss ofmore » specific epitopes from the glycome profiles in enzyme-treated plant biomass. The glycome profiling data were further substantiated by oxime-NIMS, which identified hexose products from hydrolysis of cellulose, and pentose-only and mixed hexose-pentose products from the hydrolysis of hemicelluloses. The GH10 enzyme proved to be reactive with the broadest diversity of xylose-backbone polysaccharide epitopes, but was incapable of reacting with glucose-backbone polysaccharides. In contrast, the GH5 and GH11 enzymes studied here showed the ability to react with both glucose- and xylose-backbone polysaccharides. The identification of enzyme specificity for a wide diversity of polysaccharide structures provided by glycome profiling, and the correlated identification of soluble oligosaccharide hydrolysis products provided by oxime-NIMS, offers a unique combination to understand the hydrolytic capabilities and constraints of individual enzymes as they interact with plant biomass.« less

Lanthanide Complexes with Multidentate Oxime Ligands as Single-Molecule Magnets and Atmospheric Carbon Dioxide Fixation Systems.

PubMed

Hołyńska, Małgorzata; Clérac, Rodolphe; Rouzières, Mathieu

2015-09-14

The synthesis, structure, and magnetic properties of five lanthanide complexes with multidentate oxime ligands are described. Complexes 1 and 2 (1: [La2 (pop)2 (acac)4 (CH3 OH)], 2: [Dy2 (pop)(acac)5 ]) are synthesized from the 2-hydroxyimino-N-[1-(2-pyridyl)ethylidene]propanohydrazone (Hpop) ligand, while 3, 4, and 5 (3: [Dy2 (naphthsaoH)2 (acac)4 H(OH)]⋅0.85 CH3 CN⋅1.58 H2 O; 4: [Tb2 (naphthsaoH)2 (acac)4 H(OH)]⋅0.52 CH3 CN⋅1.71 H2 O; 5: [La6 (CO3 )2 (naphthsao)5 (naphthsaoH)0.5 (acac)8 (CO3 )0.5 (CH3 OH)2.76 H5.5 (H2 O)1.24 ]⋅2.39 CH3 CN⋅0.12 H2 O) contain 1-(1-hydroxynaphthalen-2-yl)-ethanone oxime (naphthsaoH2 ). In 1-4, dinuclear [Ln2 ] complexes crystallize, whereas hexanuclear La(III) complex 5 is formed after fixation of atmospheric carbon dioxide. Dy(III) -based complexes 2 and 3 display single-molecule-magnet properties with energy barriers of 27 and 98 K, respectively. The presence of a broad and unsymmetrical relaxation mode observed in the ac susceptibility data for 3 suggest two different dynamics of the magnetization which might be a consequence of independent relaxation processes of the two different Dy(3+) ions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Macrocyclic lactones in the treatment and control of parasitism in small companion animals.

PubMed

Nolan, Thomas J; Lok, James B

2012-05-01

Macrocyclic lactones (MLs) have many anti-parasitic applications in small companion animal medicine. They were first developed as chemoprophylactics against heartworm (Dirofilaria immitis) infection to be applied monthly for retroactive killing of third- and fourth-stage larvae. ML-containing products formulated for oral (ivermectin, milbemycin oxime), topical (selamectin, moxidectin) or injectable sustained release (moxidectin, ivermectin) are approved for heartworm prevention in dogs or cats. Clearance of microfilariae and gradual or "soft" killing of adult heartworms constitute increasingly prevalent extra-label uses of MLs against D. immitis. Some commercial ML formulations contain sufficient levels of active ingredient (milbemycin oxime, selamectin, moxidectin) to support additional label claims against gastrointestinal nematode parasites such as hookworms (Ancylostoma spp.) and ascarid round worms (Toxocara spp. and Toxascaris leonina). Beyond these approved applications, safe, extra-label uses of MLs against nematodes parasitizing the urinary tract, such as Capillaria spp., and parasites of the tissues, such as Dipetalonema reconditum, Dirofilaria repens, Thelazia spp. and Spirocerca lupi, in dogs and cats as well as exotic pets have been reported. MLs as a group have intrinsic insecticidal and acaricidal activity, and topical or otic formulations of certain compounds (selamectin, moxidectin, milbemycin oxime or ivermectin) are approved for treatment and control of fleas, certain ixodid ticks, sarcoptiform and demodectic mange mites and psoroptiform ear mites. Extra-label applications of MLs against ectoparasites include notoedric mange mites, dermanyssids such as Ornythonussus bacoti, numerous species of fur mite (e.g. Cheyletiella spp. and Lynxacarus) and trombiculids ("chiggers") in cats, dogs and nontraditional or exotic pets.

Probing the Carbonyl Functionality of a Petroleum Resin and Asphaltene through Oximation and Schiff Base Formation in Conjunction with N-15 NMR

PubMed Central

Thorn, Kevin A.; Cox, Larry G.

2015-01-01

Despite recent advances in spectroscopic techniques, there is uncertainty regarding the nature of the carbonyl groups in the asphaltene and resin fractions of crude oil, information necessary for an understanding of the physical properties and environmental fate of these materials. Carbonyl and hydroxyl group functionalities are not observed in natural abundance 13C nuclear magnetic resonance (NMR) spectra of asphaltenes and resins and therefore require spin labeling techniques for detection. In this study, the carbonyl functionalities of the resin and asphaltene fractions from a light aliphatic crude oil that is the source of groundwater contamination at the long term USGS study site near Bemidji, Minnesota, have been examined through reaction with 15N-labeled hydroxylamine and aniline in conjunction with analysis by solid and liquid state 15N NMR. Ketone groups were revealed through 15N NMR detection of their oxime and Schiff base derivatives, and esters through their hydroxamic acid derivatives. Anilinohydroquinone adducts provided evidence for quinones. Some possible configurations of the ketone groups in the resin and asphaltene fractions can be inferred from a consideration of the likely reactions that lead to heterocyclic condensation products with aniline and to the Beckmann reaction products from the initially formed oximes. These include aromatic ketones and ketones adjacent to quaternary carbon centers, β-hydroxyketones, β-diketones, and β-ketoesters. In a solid state cross polarization/magic angle spinning (CP/MAS) 15N NMR spectrum recorded on the underivatized asphaltene as a control, carbazole and pyrrole-like nitrogens were the major naturally abundant nitrogens detected. PMID:26556054

Synthesis and biological evaluation of sulfur-containing shikonin oxime derivatives as potential antineoplastic agents.

PubMed

Huang, Guang; Zhao, Hui-Ran; Meng, Qing-Qing; Zhang, Qi-Jing; Dong, Jin-Yun; Zhu, Bao-Quan; Li, Shao-Shun

2018-01-01

As a continuation of our research on developing potent and potentially safe antineoplastic agents, a set of forty five sulfur-containing shikonin oxime derivatives were synthesized and evaluated for their in vitro cytotoxic activity against human colon cancer (HCT-15), gastric carcinoma (MGC-803), liver (Bel7402), breast (MCF-7) cancer cells and human skin fibroblast (HSF) cells. All the synthesized compounds exhibited potent cytotoxic activity selectively towards HCT-15 cells and did not display apparent toxicity to the normal HSF cells, some of which were more or comparatively effective to the parent compound against HCT-15, MGC-803 and Bel7402 cells. The most active agent 9m displayed high potency against human cancer cells with IC 50 ranging from 0.27 ± 0.02 to 9.23 ± 0.12 μM. The structure-activity relationships (SARs) studies suggested that the nature of substituent group in the side chain is important for antitumor potency in vitro. Additionally, nitric oxide release studies revealed that the amount of nitric oxide generated from these oxime derivatives was relatively low. Furthermore, cellular mechanism investigations indicated that compound 9m could arrest cell cycle at G1 phase and induce a strong apoptotic response in HCT-15 cells. Moreover, western blot studies revealed that compound 9m induced apoptosis through the down-regulation of Bcl-2 and up-regulation of Bax, caspase 3 and 9. For all these reasons, compound 9m hold promising potential as antineoplastic agent. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Determination of glycoside hydrolase specificities during hydrolysis of plant cell walls using glycome profiling

DOE PAGES

Walker, Johnnie A.; Pattathil, Sivakumar; Bergeman, Lai F.; ...

2017-02-02

Glycoside hydrolases (GHs) are enzymes that hydrolyze polysaccharides into simple sugars. To better understand the specificity of enzyme hydrolysis within the complex matrix of polysaccharides found in the plant cell wall, we studied the reactions of individual enzymes using glycome profiling, where a comprehensive collection of cell wall glycan-directed monoclonal antibodies are used to detect polysaccharide epitopes remaining in the walls after enzyme treatment and quantitative nanostructure initiator mass spectrometry (oxime-NIMS) to determine soluble sugar products of their reactions. Single, purified enzymes from the GH5_4, GH10, and GH11 families of glycoside hydrolases hydrolyzed hemicelluloses as evidenced by the loss ofmore » specific epitopes from the glycome profiles in enzyme-treated plant biomass. The glycome profiling data were further substantiated by oxime-NIMS, which identified hexose products from hydrolysis of cellulose, and pentose-only and mixed hexose-pentose products from the hydrolysis of hemicelluloses. The GH10 enzyme proved to be reactive with the broadest diversity of xylose-backbone polysaccharide epitopes, but was incapable of reacting with glucose-backbone polysaccharides. In contrast, the GH5 and GH11 enzymes studied here showed the ability to react with both glucose- and xylose-backbone polysaccharides. The identification of enzyme specificity for a wide diversity of polysaccharide structures provided by glycome profiling, and the correlated identification of soluble oligosaccharide hydrolysis products provided by oxime-NIMS, offers a unique combination to understand the hydrolytic capabilities and constraints of individual enzymes as they interact with plant biomass.« less

The efficacy of HI-6 DMS in a sustained infusion against percutaneous VX poisoning in the guinea-pig.

PubMed

Whitmore, C; Cook, A R; Mann, T; Price, M E; Emery, E; Roughley, N; Flint, D; Stubbs, S; Armstrong, S J; Rice, H; Tattersall, J E H

2018-09-01

Post-exposure nerve agent treatment usually includes administration of an oxime, which acts to restore function of the enzyme acetylcholinesterase (AChE). For immediate treatment of military personnel, this is usually administered with an autoinjector device, or devices containing the oxime such as pralidoxime, atropine and diazepam. In addition to the autoinjector, it is likely that personnel exposed to nerve agents, particularly by the percutaneous route, will require further treatment at medical facilities. As such, there is a need to understand the relationship between dose rate, plasma concentration, reactivation of AChE activity and efficacy, to provide supporting evidence for oxime infusions in nerve agent poisoning. Here, it has been demonstrated that intravenous infusion of HI-6, in combination with atropine, is efficacious against a percutaneous VX challenge in the conscious male Dunkin-Hartley guinea-pig. Inclusion of HI-6, in addition to atropine in the treatment, improved survival when compared to atropine alone. Additionally, erythrocyte AChE activity following poisoning was found to be dose dependent, with an increased dose rate of HI-6 (0.48mg/kg/min) resulting in increased AChE activity. As far as we are aware, this is the first study to correlate the pharmacokinetic profile of HI-6 with both its pharmacodynamic action of reactivating nerve agent inhibited AChE and with its efficacy against a persistent nerve agent exposure challenge in the same conscious animal. Copyright © 2017 Crown Copyright. Published by Elsevier B.V. All rights reserved.

Phenoseasonal variability of subcanopy PAR and the effects of photointensity and photoperiod on the physiological ecology of Lindera benzoin

NASA Astrophysics Data System (ADS)

Hudson, J. E.; Levia, D. F., Jr.; Hudson, S.; Bais, H.; Legates, D. R.

2015-12-01

This work represents a novel approach to measuring photosynthetic photon flux density (PPFD), and spatiotemporal light dynamics, by utilizing an instrument capable of providing a 15-second spatially-integrated one meter linear average of the PPFD, obtaining measurements at multiple locations and elevations in the subcanopy over a full year for all cloud conditions. Nearly 4,600 individual observations of photosynthetically active radiation (PAR, 400-700 nm) were made over the seven phenoseasons of a deciduous forest in the Piedmont Region, Maryland. Additionally, to quantify of the effect of various photointensities on the physiological ecology of Lindera benzoin L. Blume (northern spicebush) grown in the lab, health was determined by monitoring physical growth and biomass, and by UV-vis spectrophotometry analysis of leaf extract. Results show understory PAR is typically less than 40% of open PAR. Leafless subcanopy PAR values were almost 10 times higher than leafed season PAR, and sunflecks often three orders of magnitude higher than mean subcanopy PAR during the leafed season. Phenoseason is responsible for nearly three-quarters of the variation between plant canopy levels. Spicebush growth occurred at study locations receiving higher incidence of PAR (> 64th percentile). UV-vis spectrophotometry analysis showed significant differences in root to shoot ratios, biomass, initial stomatal conductance, chlorophyll a and b, and carotenoids. Spicebush under lab conditions significantly alter their biomass and individual pigments and pigment ratios in response to high intensity light conditions. Results suggest temporal light sequences in the field may be a very important factor in the functional ecology of northern spicebush.

Catalytic soman scavenging by Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes

PubMed Central

Kovarik, Zrinka; Hrvat, Nikolina Maček; Katalinić, Maja; Sit, Rakesh K.; Paradyse, Alexander; Žunec, Suzana; Musilek, Kamil; Fokin, Valery V.; Taylor, Palmer; Radić, Zoran

2016-01-01

Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman. HI-6 was previously shown in vitro to efficiently reactivate this mutant upon soman, as well as VX, cyclosarin, sarin and paraoxon inhibition. We here demonstrate that ex vivo, in whole human blood, 1 μM soman was detoxified within 30 minutes when supplemented with 0.5 μM Y337A/F338A AChE and 100 μM HI-6. This combination was further tested in vivo. Catalytic scavenging of soman in mice improved the therapeutic outcome and resulted in the delayed onset of toxicity symptoms. Furthermore, in a preliminary in vitro screen we identified an even more efficacious oxime than HI-6, in a series of forty-two pyridinium aldoximes, and five imidazole 2-aldoxime N-propyl pyridinium derivatives. One of the later imidazole aldoximes, RS-170B, was a 2–3 –fold more effective reactivator of Y337A/F338A AChE than HI-6 due to the smaller imidazole ring, as indicated by computational molecular models, that affords a more productive angle of nucleophilic attack. PMID:25835984

Treatment of third-stage larvae of Toxocara cati with milbemycin oxime plus praziquantel tablets and emodepside plus praziquantel spot-on formulation in experimentally infected cats.

PubMed

Wolken, Sonja; Böhm, Claudia; Schaper, Roland; Schnieder, Thomas

2012-11-01

Toxocara cati is the most prevalent gastrointestinal helminth in cats worldwide, with cats of all ages at risk of infection. An anthelminthic treatment that not only affects the gut-dwelling stages of this parasite but is also effective against developmental stages in the tissue has the advantage that the pathology caused by migrating larvae is minimized and the need for repeated treatments is reduced. This study was conducted to evaluate the efficacy of milbemycin oxime/praziquantel tablets (Milbemax®, Novartis) against third-stage larvae of T. cati in comparison to a spot-on formulation of emodepside and praziquantel (Profender®, Bayer). Twenty-four kittens were experimentally infected with T. cati and randomly allocated to three study groups. Treatments were performed at the minimum therapeutic dosage 5 days after the experimental infection. The development of patent infections was monitored and all cats were dewormed 50 days post-infection. Efficacies were calculated based on counts of excreted worms in the treated groups compared to a negative control group. Seven of the eight cats in the negative control group developed a patent T. cati infection and all cats were excreting worms at the end of the study (geometric mean worm count 18.1). No efficacy could be observed for the milbemycin oxime-treated animals. All cats developed a patent infection and excreted worms (geometric mean worm count 27.7). The treatment with Profender® was 98.5 % effective against L3 of T. cati. One cat developed a patent infection and was excreting worms at the end of the study (geometric mean worm count 0.3). No adverse reactions were noted in either treatment group.

Probing the carbonyl functionality of a petroleum resin and asphaltene through oximation and schiff base formation in conjunction with N-15 NMR

USGS Publications Warehouse

Thorn, Kevin A.; Cox, Larry G.

2015-01-01

Despite recent advances in spectroscopic techniques, there is uncertainty regarding the nature of the carbonyl groups in the asphaltene and resin fractions of crude oil, information necessary for an understanding of the physical properties and environmental fate of these materials. Carbonyl and hydroxyl group functionalities are not observed in natural abundance 13C nuclear magnetic resonance (NMR) spectra of asphaltenes and resins and therefore require spin labeling techniques for detection. In this study, the carbonyl functionalities of the resin and asphaltene fractions from a light aliphatic crude oil that is the source of groundwater contamination at the long term USGS study site near Bemidji, Minnesota, have been examined through reaction with 15N-labeled hydroxylamine and aniline in conjunction with analysis by solid and liquid state 15N NMR. Ketone groups were revealed through 15N NMR detection of their oxime and Schiff base derivatives, and esters through their hydroxamic acid derivatives. Anilinohydroquinone adducts provided evidence for quinones. Some possible configurations of the ketone groups in the resin and asphaltene fractions can be inferred from a consideration of the likely reactions that lead to heterocyclic condensation products with aniline and to the Beckmann reaction products from the initially formed oximes. These include aromatic ketones and ketones adjacent to quaternary carbon centers, β-hydroxyketones, β-diketones, and β-ketoesters. In a solid state cross polarization/magic angle spinning (CP/MAS) 15N NMR spectrum recorded on the underivatized asphaltene as a control, carbazole and pyrrole-like nitrogens were the major naturally abundant nitrogens detected.

Combined application of plasma mutagenesis and gene engineering leads to 5-oxomilbemycins A3/A4 as main components from Streptomyces bingchenggensis.

PubMed

Wang, Hai-Yan; Zhang, Ji; Zhang, Yue-Jing; Zhang, Bo; Liu, Chong-Xi; He, Hai-Rong; Wang, Xiang-Jing; Xiang, Wen-Sheng

2014-12-01

Milbemycin oxime has been commercialized as effective anthelmintics in the fields of animal health, agriculture, and human infections. Currently, milbemycin oxime is synthesized by a two-step chemical reaction, which involves the ketonization of milbemycins A3/A4 to yield the intermediates 5-oxomilbemycins A3/A4 using CrO3 as catalyst. Due to the low efficiency and environmental unfriendliness of the ketonization of milbemycins A3/A4, it is imperative to develop alternative strategies to produce 5-oxomilbemycins A3/A4. In this study, the atmospheric and room temperature plasma (ARTP) mutation system was first employed to treat milbemycin-producing strain Streptomyces bingchenggensis, and a mutant strain BC-120-4 producing milbemycins A3, A4, B2, and B3 as main components was obtained, which favors the construction of genetically engineered strains producing 5-oxomilbemycins. Importantly, the milbemycins A3/A4 yield of BC-120-4 reached 3,890 ± 52 g/l, which was approximately two times higher than that of the initial strain BC-109-6 (1,326 ± 37 g/l). The subsequent interruption of the gene milF encoding a C5-ketoreductase responsible for the ketonization of milbemycins led to strain BCJ60 (∆milF) with the production of 5-oxomilbemycins A3/A4 and the elimination of milbemycins A3, A4, B2, and B3. The high 5-oxomilbemycins A3/A4 yield (3,470 ± 147 g/l) and genetic stability of BCJ60 implied the potential use in industry to prepare 5-oxomilbemycins A3/A4 for the semisynthesis of milbemycins oxime.

Glycoproteomics enabled by tagging sialic acid- or galactose-terminated glycans

PubMed Central

Ramya, T N C; Weerapana, Eranthie; Cravatt, Benjamin F; Paulson, James C

2013-01-01

In this paper, we present two complementary strategies for enrichment of glycoproteins on living cells that combine the desirable attributes of “robust enrichment” afforded by covalent-labeling techniques and “specificity for glycoproteins” typically provided by lectin or antibody affinity reagents. Our strategy involves the selective introduction of aldehydes either into sialic acids by periodate oxidation (periodate oxidation and aniline-catalyzed oxime ligation (PAL)) or into terminal galactose and N-acetylgalactosamine residues by galactose oxidase (galactose oxidase and aniline-catalyzed oxime ligation (GAL)), followed by aniline-catalyzed oxime ligation with aminooxy-biotin to biotinylate the glycans of glycoprotein subpopulations with high efficiency and cell viability. As expected, the two methods exhibit reciprocal tagging efficiencies when applied to fully sialylated cells compared with sialic acid-deficient cells. To assess the utility of these labeling methods for glycoproteomics, we enriched the PAL- and GAL-labeled (biotinylated) glycoproteome by adsorption onto immobilized streptavidin. Glycoprotein identities (IDs) and N-glycosylation site information were then obtained by liquid chromatography-tandem mass spectrometry on total tryptic peptides and on peptides subsequently released from N-glycans still bound to the beads using peptide N-glycosidase F. A total of 175 unique N-glycosylation sites were identified, belonging to 108 nonredundant glycoproteins. Of the 108 glycoproteins, 48 were identified by both methods of labeling and the remainder was identified using PAL on sialylated cells (40) or GAL on sialic acid-deficient cells (20). Our results demonstrate that PAL and GAL can be employed as complementary methods of chemical tagging for targeted proteomics of glycoprotein subpopulations and identification of glycosylation sites of proteins on cells with an altered sialylation status. PMID:23070960

In vitro degradation and antitumor activity of oxime bond-linked daunorubicin-GnRH-III bioconjugates and DNA-binding properties of daunorubicin-amino acid metabolites.

PubMed

Orbán, Erika; Mezo, Gábor; Schlage, Pascal; Csík, Gabriella; Kulić, Zarko; Ansorge, Philipp; Fellinger, Erzsébet; Möller, Heiko Michael; Manea, Marilena

2011-07-01

Bioconjugates with receptor-mediated tumor-targeting functions and carrying cytotoxic agents should enable the specific delivery of chemotherapeutics to malignant tissues, thus increasing their local efficacy while limiting the peripheral toxicity. In the present study, gonadotropin-releasing hormone III (GnRH-III; Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH(2)) was employed as a targeting moiety to which daunorubicin was attached via oxime bond, either directly or by insertion of a GFLG or YRRL tetrapeptide spacer. The in vitro antitumor activity of the bioconjugates was determined on MCF-7 human breast and HT-29 human colon cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Their degradation/stability (1) in human serum, (2) in the presence of cathepsin B and (3) in rat liver lysosomal homogenate was analyzed by liquid chromatography in combination with mass spectrometry. The results show that (1) all synthesized bioconjugates have in vitro antitumor effect, (2) they are stable in human serum at least for 24 h, except for the compound containing an YRRL spacer and (3) they are hydrolyzed by cathepsin B and in the lysosomal homogenate. To investigate the relationship between the in vitro antitumor activity and the structure of the bioconjugates, the smallest metabolites produced in the lysosomal homogenate were synthesized and their binding to DNA was assessed by fluorescence spectroscopy. Our data indicate that the incorporation of a peptide spacer in the structure of oxime bond-linked daunorubicin-GnRH-III bioconjugates is not required for their antitumor activity. Moreover, the antitumor activity is influenced by the structure of the metabolites (daunorubicin-amino acid derivatives) and their DNA-binding properties.

Efficacy of a single dose of milbemycin oxime/praziquantel combination tablets, Milpro(®), against adult Echinococcus multilocularis in dogs and both adult and immature E. multilocularis in young cats.

PubMed

Cvejic, Dejan; Schneider, Claudia; Fourie, Josephus; de Vos, Christa; Bonneau, Stephane; Bernachon, Natalia; Hellmann, Klaus

2016-03-01

Two single-site, laboratory, negatively controlled, masked, randomised dose confirmation studies were performed: one in dogs, the other in cats. After a period of acclimatisation, both the dogs and cats were orally infected with Echinococcus multilocularis protoscoleces. In the dog study, 10 dogs received a single dose of Milpro® tablets at a minimum dose of 0.5 mg/kg milbemycin oxime and 5 mg/kg praziquantel 18 days post-infection and 10 dogs received no treatment. In the cat study, 10 cats received a single dose of Milpro® tablets at a minimum dose of 2 mg/kg milbemycin oxime and 5 mg/kg praziquantel 7 days post-infection, 10 cats received a single dose of the treatment 18 days post-infection and 10 cats remained untreated. In both studies, intestinal worm counts were performed 23 days post-infection at necropsy. No worms were retrieved from any of the 30 treated animals. Nine of 10 control dogs had multiple worms (geometric mean 91, arithmetic mean 304) and all 10 control cats had multiple worms (geometric mean 216, arithmetic mean 481). The difference in worm counts between all three treated groups and their controls was highly significant (ANOVA p values of log transformed data <0.0001). Efficacy of 100 % was demonstrated for the elimination of adult E. multilocularis in dogs and cats as well as for elimination of immature E. multilocularis in cats as evidenced by the effectiveness of treatment 7 days post-infection. The treatments were well accepted and tolerated, and there were no adverse drug reactions observed.

In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase.

PubMed

Atanasov, Vasil N; Petrova, Iskra; Dishovsky, Christophor

2013-03-25

Organophosphorus compounds (OPC) were developed as warfare nerve agents. They are also widely used as pesticides. The drug therapy of intoxication with OPC includes mainly combination of cholinesterase (ChE) reactivators and cholinolytics. There is no single ChE reactivator having an ability to reactivate sufficiently the inhibited enzyme due to the high variability of chemical structure of the inhibitors. The difficulties in reactivation of ChE activity and slight antidote effect regarding intoxication with some OPC are some of the reasons for continuous efforts to obtain new reactivators of ChE. The aim of the present study was to evaluate the efficacy of some ChE reactivators against OPC intoxication (tabun, paraoxon and dichlorvos) in in vitro experiments and to compare their activity to that known for some currently used oximes (obidoxime, HI-6, 2-PAM). Experiments were carried out using rat brain acetylcholinesterase (AChE). Reactivators showed different activity in the reactivation of rat brain AChE after dichlorvos, paraoxon and tabun inhibition. AChE was easier reactivated after paraoxon treatment. The best effect showed BT-07-4M, obidoxime, TMB-4 and BT-08 from the group of symmetric oximes, and Toxidin, BT-05 and BT-03 from asymmetric compounds. The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. All compounds showed low activity toward inhibition of AChE caused by dichlorvos. Comparison of two main structure types (symmetric/asymmetric) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Photoinitiated polymerization of 1-vinylimidazole

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

Joshi, M.G.; Rodriguez, F.

1984-04-01

The photoinitiated polymerization of 1-vinylimidazole (VI) does not follow the classical kinetic scheme for free radical polymerization. Kinetic results for VI suggest a degradative addition reaction between the macroradical and the monomer to produce a relatively stable, unreactive radical, which does not reinitiate polymerization, is low, 1.5 kcal/mol. Among the 3 photoinitiators used, the highest quantum efficiency was demonstrated by 2,2'-diethoxyacetophenone followed by bezoin methyl ether and benzoin isopropyl ether. Under the experimental conditions used, the polymerization of VI does not proceed to complete conversion, and the phenomenon of dead-end polymerization is observed.

The laser versus the lamp: Reactivity of the diphenyl ketyl radical in the ground and excited states

NASA Astrophysics Data System (ADS)

Baumann, H.; Merckel, C.; Timpe, H.-J.; Graness, A.; Kleinschmidt, J.; Gould, I. R.; Turro, N. J.

1984-01-01

The diphenyl ketyl radical which is formed upon photolysis of α-phenyl benzoin is produced in its excited state upon intense pulsed laser irradiation. Using the techniques of time-resolved absorption and emission spectroscopy, reaction rate constants for the ground and excited states of this radical were obtained. For the radical quenchers employed, the excited state reactivity is found to be typically several orders of magnitude greater than that of the ground state. It is concluded that the excited state of diphenyl ketyl radical reacts predominantly by electron transfer processes.

15N and13C NMR investigation of hydroxylamine-derivatized humic substances

USGS Publications Warehouse

Thorn, K.A.; Arterburn, J.B.; Mikita, M.A.

1992-01-01

Five fulvic and humic acid samples of diverse origins were derivatized with 15N-labeled hydroxylamine and analyzed by liquid-phase 15N NMR spectrometry. The 15N NMR spectra indicated that hydroxylamine reacted similarly with all samples and could discriminate among carbonyl functional groups. Oximes were the major derivatives; resonances attributable to hydroxamic acids, the reaction products of hydroxylamine with esters, and resonances attributable to the tautomeric equilibrium position between the nitrosophenol and monoxime derivatives of quinones, the first direct spectroscopic evidence for quinones, also were evident. The 15N NMR spectra also suggested the presence of nitriles, oxazoles, oxazolines, isocyanides, amides, and lactams, which may all be explained in terms of Beckmann reactions of the initial oxime derivatives. INEPT and ACOUSTIC 15N NMR spectra provided complementary information on the derivatized samples. 13C NMR spectra of derivatized samples indicated that the ketone/quinone functionality is incompletely derivatized with hydroxylamine. ?? 1991 American Chemical Society.

Clinicopathologic findings, sensitivity to house dust mites and efficacy of milbemycin oxime treatment of dogs with Cheyletiella sp. infestation.

PubMed

White, S D; Rosychuk, R A; Fieseler, K V

2001-02-01

Twenty-three dogs with positive skin scrapings for Cheyletiella sp. were treated with milbemycin oxime using a protocol approximating 2 mg kg-1 orally once weekly for three weeks. Nineteen of these dogs belonged to a household of 41 dogs and two dogs were in households with one other dog. All in-contact dogs were treated. Pre-treatment intradermal skin tests showed positive reactions to D. farinae in 13 dogs and to D. pteronyssinus in 12 dogs; these became negative post-treatment in four and seven dogs, respectively. All dogs showed a dramatic reduction in clinical signs one week after the third treatment. Eighteen dogs no longer had mites on skin scrapings, three had dead mites and two had deformed eggs. Recurrence of clinical signs necessitated two additional courses of the protocol in the multiple dog household and for a dog receiving immunosuppressive treatment for pemphigus foliaceus. Possible adverse reactions to the milbemycin (vomiting, lethargy) were noted once in two dogs.

Role of glutamate-199 in the aging of cholinesterase. (Reannouncement with new availability information)

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

Saxena, A.; Doctor, B.P.; Maxwell, D.M.

1993-11-30

Aging of organophosphate-conjugated acetylcholinesterase results from the loss of an alkoxy group with concomitant stabilization of the conjugate to spontaneous or nucleophile-induced deacylation. We have examined the kinetics of aging in a pinacolylmethylphosphonofluoridate (soman)-inhibited mutant enzyme in which the glutamate (E199) located at the amino-terminal to the active-site sense (S200) was converted to glutamine (Q). For wild type enzyme, the soman-acetylcholinesterase conjugate aged immediately, giving rise to a form of enzyme resistant to reactivation by oximes. In contrast, the E199Q mutant enzyme was largely resistant to aging and could be reactivated by oximes. Since the pH dependence for aging wasmore » not altered appreciably, the primary influence of the loss of charge appears to be on the intrinsic rate of aging. The negative charge on E199 likely imparts an inductive effect on the conjugated organophosphate to facilitate removal of the alkoxy group. Cholinesterases, Aging, Organophosphate.« less

21 CFR 520.1441 - Milbemycin oxime.

Code of Federal Regulations, 2014 CFR

2014-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... hookworm, roundworm, and whipworm, use 0.23 milligram per pound of body weight (0.5 milligram per kilogram). For heartworm, use 0.05 milligram per pound of body weight (0.1 milligram per kilogram). (ii...

21 CFR 520.1441 - Milbemycin oxime.

Code of Federal Regulations, 2013 CFR

2013-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... hookworm, roundworm, and whipworm, use 0.23 milligram per pound of body weight (0.5 milligram per kilogram). For heartworm, use 0.05 milligram per pound of body weight (0.1 milligram per kilogram). (ii...

21 CFR 522.1862 - Sterile pralidoxime chloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sterile pralidoxime chloride. 522.1862 Section 522....1862 Sterile pralidoxime chloride. (a) Chemical name. 2-Formyl-1-methylpyridinium chloride oxime. (b) Specifications. Sterile pralidoxime chloride is packaged in vials. Each vial contains 1 gram of sterile...

Heteropolyhedral silver compounds containing the polydentate ligand N,N,O-E-[6-(hydroxyimino)ethyl]-1,3,7-trimethyllumazine. Preparation, spectral and XRD structural study and AIM calculations.

PubMed

Jiménez-Pulido, Sonia B; Hueso-Ureña, Francisco; Fernández-Liencres, M Paz; Fernández-Gómez, Manuel; Moreno-Carretero, Miguel N

2013-01-14

The oxime derived from 6-acetyl-1,3,7-trimethyllumazine (1) ((E-6-(hydroxyimino)ethyl)-1,3,7-trimethylpteridine-2,4(1H,3H)-dione, DLMAceMox) has been prepared and its molecular and crystal structure determined from spectral and XRD data. The oxime ligand was reacted with silver nitrate, perchlorate, thiocyanate, trifluoromethylsulfonate and tetrafluoroborate to give complexes with formulas [Ag(2)(DLMAceMox)(2)(NO(3))(2)](n) (2), [Ag(2)(DLMAceMox)(2)(ClO(4))(2)](n) (3), [Ag(2)(DLMAceMox)(2)(SCN)(2)] (4), [Ag(2)(DLMAceMox)(2)(CF(3)SO(3))(2)(CH(3)CH(2)OH)]·CH(3)CH(2)OH (5) and [Ag(DLMAceMox)(2)]BF(4) (6). Single-crystal XRD studies show that the asymmetrical residual unit of complexes 2, 3 and 5 contains two quite different but connected silver centers (Ag1-Ag2, 2.9-3.2 Å). In addition to this, the Ag1 ion displays coordination with the N5 and O4 atoms from both lumazine moieties and a ligand (nitrato, perchlorato or ethanol) bridging to another disilver unit. The Ag2 ion is coordinated to the N61 oxime nitrogens, a monodentate and a (O,O)-bridging nitrato/perchlorato or two monodentate O-trifluoromethylsulfonato anions. The coordination polyhedra can be best described as a strongly distorted octahedron (around Ag1) and a square-based pyramid (around Ag2). The Ag-N and Ag-O bond lengths range between 2.22-2.41 and 2.40-2.67 Å, respectively. Although the structure of 4 cannot be resolved by XRD, it is likely to be similar to those described for 2, 3 and 5, containing Ag-Ag units with S-thiocyanato terminal ligands. Finally, the structure of the tetrafluoroborate compound 6 is mononuclear with a strongly distorted tetrahedral AgN(4) core (Ag-N, 2.27-2.43 Å). Always, the different Ag-N distances found clearly point to the more basic character of the oxime N61 nitrogen atom when compared with the pyrazine N5 one. A topological analysis of the electron density within the framework provided by the quantum theory of atoms in molecules (QTAIM) using DFT(M06L) levels of theory has been performed. Every Ag-Ag and Ag-ligand interaction has been characterized in terms of Laplacian of the electron density, [nabla](2)ρ(r), and the total energy density, H(r).

Evaluation of the efficacy of monthly oral administration of afoxolaner plus milbemycin oxime (NexGard Spectra(®), Merial) in the prevention of adult Spirocerca lupi establishment in experimentally infected dogs.

PubMed

Beugnet, Frederic; Crafford, Dionne; de Vos, Christa; Kok, Dawid; Larsen, Diane; Fourie, Josephus

2016-08-15

The nematode Spirocerca lupi (Rudolphi, 1809) is widely distributed but mostly occurs sporadically with stable populations only in certain geographic areas. This helminth mainly infects dogs and wild canids. Primary pathology relates to migration of third stage larvae (L3) damaging the thoracic aorta and establishment of adults in nodules in the oesophagus. The objective of the present study was to evaluate the efficacy of milbemycin oxime in combination with afoxolaner (NexGard Spectra(®), Merial), administered monthly, in preventing establishment of adult worms after experimental infection. Two groups consisting of eight animals each were experimentally infected with 15 L3 on Days -28, -14 and -2, respectively (45 L3 per animal in total). Group 1 dogs served as untreated (negative) control, whereas animals in group 2 were treated with NexGard Spectra(®) at a minimum dose of 0.5mg/kg milbemycin oxime on Day 0 and from then onwards every 28 days up to Day 140 (six treatment occasions). Endoscopy was performed on Day 112 and for some animals also Day 140. Necropsy for worm recovery and nodule/lesion scoring was performed on Day 168. All eight animals in the control group (group 1) presented with 1-3 nodules and worm counts ranging from 9 to 41. Six animals in the NexGard Spectra(®) group presented with 1-4 nodules and worm counts ranging from 1 to 5. Significantly (p<0.05) fewer worms were collected from treated animals in the treated group (geometric mean 1.7) versus the negative control group (geometric mean 22.0) with 92.3% efficacy calculated. There was no significant (p>0.05) difference between groups with reference to number of nodules in the oesophagus. However, nodules in the control group were significantly (p<0.05) larger than those in the treated group. Number and size of lesions in the dorsal aorta did not differ statistically between groups 1 and 2. Because NexGard Spectra(®) was administered 28 days after onset of inoculation, migrating and developing L3 caused damage to the aorta wall of animals in the treated group. Milbemycin oxime (administered as NexGard Spectra(®)) demonstrated effectiveness in reducing infection with adult Spirocerca lupi worms in the oesophagus. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Therapeutic efficacy of milbemycin oxime/praziquantel oral formulation (Milbemax®) against Thelazia callipaeda in naturally infested dogs and cats

PubMed Central

2012-01-01

Background Over the last few decades, canine and feline thelaziosis caused by Thelazia callipaeda eye worms has gained the attention of the veterinary community due to the spread of this ocular infestation in geographical areas previously regarded as non endemic. The therapeutic efficacy of milbemycin oxime/praziquantel tablets (Milbemax®) against T. callipaeda was tested in naturally infested dogs and cats. Methods From January 2009 to July 2011 a placebo controlled and randomized field study was conducted in T. callipaeda endemic areas of Switzerland (CH) and Italy (ITA) involving client-owned animals. Dogs (n = 56) and cats (n = 31) were physically examined at enrolment Day 0 (D0) and twice afterwards (D7 and D14). Infested animals were orally treated with Milbemax® or with placebo tablets on D0 and, if an animal was found still infested with T. callipaeda, also on D7. On D14 nematodes were flushed from the conjunctiva, identified and counted. Results Out of 56 dogs, 43 were included in the statistical analysis, whereas 13 were excluded because the products under investigation were not administered with food, as required by the label. On D7 and D14, 72.7% and 90.9% of treated dogs were eye worm free, whereas in the placebo group 95.2% and 76.2% still harbored nematodes, resulting in a mean percentage worm count reduction for the Milbemax® group of 86.1% and 96.8%, respectively. Both results were significantly higher (p = 0.0001) than the placebo group. Out of the 31 cats included in the study at D7 and D14, 53.3% and 73.3% treated with Milbemax® were free of T. callipaeda, while 81.3% and 73.3 in the placebo group were still harbouring eye worms, resulting in a mean percentage worm count reduction for the treated group of 62.2% and 80.0%, respectively. Both results were significantly higher (p = 0.0106 and p = 0.0043) than the placebo group. Conclusions The commercial formulation of milbemycin oxime at the minimal dose of 0.5 mg/kg and 2 mg/k in dogs and cats, respectively, showed a high therapeutic efficacy in curing T. callipaeda infestations. The advantages of an oral application are additionally increased by the large spectrum of activity of praziquantel and milbemycin oxime against Cestodes and Nematodes infesting dogs and cats. PMID:22541136

A DFT study on NHC-catalyzed intramolecular aldehyde-ketone crossed-benzoin reaction: mechanism, regioselectivity, stereoselectivity, and role of NHC.

PubMed

Zhang, Wei; Wang, Yang; Wei, Donghui; Tang, Mingsheng; Zhu, Xinju

2016-07-06

A systematic theoretical study has been carried out to understand the mechanism and stereoselectivity of N-heterocyclic carbene (NHC)-catalyzed intramolecular crossed-benzoin reaction of enolizable keto-aldehyde using density functional theory (DFT) calculations. The calculated results reveal that the most favorable pathway contains four steps, i.e., the nucleophilic attack of NHC on the carbonyl carbon atom of a formyl group, the formation of a Breslow intermediate, a ring-closure process coupled with proton transfer, and regeneration of the catalyst. For the formation of the Breslow intermediate via the [1,2]-proton transfer process, apart from the direct proton transfer mechanism, the base Et3N and the in situ generated Brønsted acid Et3N·H(+) mediated proton transfer mechanisms have also been investigated; the free energy barriers for the crucial proton transfer steps are found to be significantly lowered by explicit inclusion of the Brønsted acid Et3N·H(+). The computational results show that the ring-closure process is the stereoselectivity-determining step, in which two chirality centers assigned on the coupling carbon atoms are formed, and the S-configured diastereomer is the predominant product, which is in good agreement with the experimental observations. NCI and NBO analyses are employed to disclose the origin of stereoselectivity and regioselectivity. Moreover, a global reaction index (GRI) analysis has been performed to confirm that NHC mainly plays the role of a Lewis base. The mechanistic insights obtained in the present study should be valuable for the rational design of an effective organocatalyst for this kind of reaction with high stereoselectivity and regioselectivity.

21 CFR 520.1445 - Milbemycin oxime tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

....1445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... puppies—(i) Amount. For hookworm, roundworm, and whipworm, use 0.23 milligram per pound of body weight (0.5 milligram per kilogram). For heartworm, use 0.05 milligram per pound of body weight (0.1 milligram...

77 FR 47511 - New Animal Drugs; Cephalexin; Fentanyl; Milbemycin Oxime and Praziquantel

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-09

.... Chewable Tablets for treatment of secondary 520.376 Worth, TX 76137. Dogs. superficial bacterial pyoderma in dogs caused by susceptible strains of Staphylococcus pseudintermedius. 141-337 Nexcyon RECUVYRA... 53703. dogs. 141-338 Novartis Animal INTERCEPTOR SPECTRUM Original approval for New yes CE \\1\\ Health US...

Time-resolved ESR spectra of the α-hydroxybenzyl-amine complex

NASA Astrophysics Data System (ADS)

Kawai, Akio; Kobori, Yasuhiro; Obi, Kinichi

1993-11-01

Time-resolved ESR spectra of the α-hydroxybenzyl radical were measured in benzene and 2-propanol solutions by the photo-dissociation of benzoin. The hyperfine structure (hfs) of α-hydroxybenzyl depends on the solvents. In a benzene solution containing triethylamine, two species with different hyperfine structure appeared simultaneously. As the ratio of intensity for the two species depends on the concentration of triethylamine, one of them is assigned to the bare α-hydroxybenzyl and the other to the 1:1 complex of α-hydroxybenzyl and triethylamine. The equilibrium constant of complex formation was estimated to be about 450 M -1 from the analysis of CIDEP intensities.

21 CFR 520.2134 - Spinosad and milbemycin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... a minimum dosage of 13.5 mg/pound (lb) (30 mg/kilogram (kg)) of body weight spinosad and 0.2 mg/lb (0.5 mg/kg) of body weight milbemycin oxime. (2) Indications for use. To kill fleas; for the...

21 CFR 520.2134 - Spinosad and milbemycin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... a minimum dosage of 13.5 mg/pound (lb) (30 mg/kilogram (kg)) of body weight spinosad and 0.2 mg/lb (0.5 mg/kg) of body weight milbemycin oxime. (2) Indications for use. To kill fleas; for the...

21 CFR 520.2134 - Spinosad and milbemycin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... a minimum dosage of 13.5 mg/pound (lb) (30 mg/kilogram (kg)) of body weight spinosad and 0.2 mg/lb (0.5 mg/kg) of body weight milbemycin oxime. (2) Indications for use. To kill fleas; for the...

21 CFR 520.2134 - Spinosad and milbemycin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... a minimum dosage of 13.5 mg/pound (lb) (30 mg/kilogram (kg)) of body weight spinosad and 0.2 mg/lb (0.5 mg/kg) of body weight milbemycin oxime. (2) Indications for use. To kill fleas; for the...

In vivo Oxime Administration Does Not Influence Ellman Acetylcholinesterase Assay Results

DTIC Science & Technology

2009-01-01

8217 -dithiobis(2-nitrobenwic acid), bicinchoninic acid (BCA) Protein Assay Reagent A (sodium carbonate, sodium bicarbonate , BCA- detection reagent, and...ToxIcoI24:429-435. PeD’Oianu GA.. 2007. Letter to the Editor: Cholin e.ra. e p.seudo-activity. oxImolys i~, estcrolysls, thiocholiDe ester

Radioimmunoassay for colchicine: synthesis and properties of three haptens.

PubMed

Pontikis, R; Scherrmann, J M; Nguyen, H N; Boudet, L; Pichat, L

1980-01-01

For the development of radioimmunoassay procedures for colchicine, three haptens, N-ethylamino-colchiceinamide, 4-formylchochicine - (O-carboxymethyl) oxime and 4-hydroxymethylcolchicine O-hemisuccinic acid were synthetized and characterized by mass and proton magnetic resonance spectrometries. The conjugates obtained by coupling the haptens to bovine serum albumin were employed to immunize rabbits and goats.

SUPPORTED LIX-84 LIQUID MEMBRANES FOR METAL ION SEPARATION: A STUDY ON METAL ION SORPTION EQUILIBRIUM AND KINETICS

EPA Science Inventory

Supported 2-hydroxy-5-nonyl-acetophenone oxime (LIX-84) liquid membranes have potential applications for the removal (or recovery) of copper ions from waste streams. But, the stability of such a liquid membrane remains the major hurdle for its practical applications. Inorganic su...

SYNTHESIS AND CHARACTERIZATION OF LIX-84 NON-COVALENTLY BOUND SILICA SORBENTS FOR METAL-ION RECOVERY

EPA Science Inventory

Mesoporous silica particles were modified with LIX-84: (2-hydroxy-5-nonylacetophenome oxime). The LIX-84: was attached to the surface of silica via non-covelent forces. The effects of silica particle size, temperature, and pH on metal ion adsorption properties were studied and co...

Cortical perfusion response to an electrical stimulation of the auditory nerve in profoundly deaf patients: study with technetium-99m hexamethylpropylene amine oxime single photon emission tomography.

PubMed

Le Scao, Y; Robier, A; Baulieu, J L; Beutter, P; Pourcelot, L

1992-01-01

Brain activation procedures associated with single photon emission tomography (SPET) have recently been developed in healthy controls and diseased patients in order to help in their diagnosis and treatment. We investigated the effects of a promontory test (PT) on the cerebral distribution of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) in 7 profoundly deaf patients, 6 PT+ and one PT-. The count variation in the temporal lobe was calculated on 6 coronal slices using the ratio (Rstimulation-Rdeprivation)/Rdeprivation where R = counts in the temporal lobe/whole-brain count. A count increase in the temporal lobe was observed in all patients and was higher in all patients with PT+ than in the patient with PT-. The problems of head positioning and resolution of the system were taken into account, and we considered that the maximal count increment was related to the auditory cortex response to the stimulus. Further clinical investigations with high-resolution systems have to be performed in order to validate this presurgery test in cochlear implant assessment.

Oxime Ether Lipids as Transfection Agents: Assembly and Complexation with siRNA.

PubMed

Puri, Anu; Zampino, Serena; Viard, Mathias; Shapiro, Bruce A

2017-01-01

RNAi-based therapeutic approaches to combat cancer and other diseases are currently an area of great interest. However, practical applications of this approach rely on optimal tools to carry and deliver siRNA to the desired site. Oxime ether lipids (OELs) are a class of molecules among other various carriers being examined for siRNA delivery. OELs, relatively new candidates, belong to a class of non-glycerol based lipids and have begun to claim their place as an siRNA delivery carrier in the field of RNAi therapy. Chemical synthesis steps of OELs are considered relatively simple with the ability to modify the functionalities as desired. OEL-siRNA complexes can be assembled in the presence of serum-containing buffers (or cell culture media) and recent data from our and other groups have demonstrated that OELs are viable carriers for siRNA delivery in the cell culture systems. In this chapter, we provide the details of experimental protocols routinely used in our laboratory to examine OEL-siRNA complexes including their assembly, stability, and transfection efficiencies.

Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning.

PubMed

Herbert, Julia; Thiermann, Horst; Worek, Franz; Wille, Timo

2017-08-15

Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning. Aim of this study was the development of an applicable and easy method to test the therapeutic efficiency of such substances. For this purpose, airway responsiveness in viable precision cut lung slices (PCLS) from rats was analysed. We showed that ACh-induced airway contractions were spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, contractions were irreversible. This effect could be antagonized by addition of the standard therapeutic atropine, thereby presenting a clear indication for treatment efficiency. Now, candidate therapeutic compounds can be evaluated, based on their ability to counteract the irreversible airway contraction in OP poisoned PCLS. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis, structural studies and antimicrobial activity of N'-((2Z, 3E)-3-(hydroxyimino)butan-2-ylidene)-2-phenylacetohydrazide and its Co(II), Ni(II) complexes

NASA Astrophysics Data System (ADS)

Karadeniz, Şeyma; Ataol, Cigdem Yuksektepe; Şahin, Onur; İdil, Önder; Bati, Hümeyra

2018-06-01

A new aroylhydrazoneoxime, N'-((2Z, 3E)-3-(hydroxyimino)butan-2-ylidene)-2-phenylacetohydrazide ligand (LH2) and its Ni(II) and Co(II) complexes, have been synthesized and characterized by elemental and thermal analyses, IR and UV-vis spectroscopy, magnetic moment and X-ray diffraction. The antimicrobial activities of these compounds were tested by using minimal inhibitory concentration method (MIC). The ligand-containing aroylhydrazone and oxime groups and its Ni complex crystallize in the triclinic system and P 1 - space group, while its Co complex crystallizes in the monoclinic system and the C 2/c space group. X-ray results show that the ligand in the keto form is transformed into enolic form when it forms coordination. From elemental analysis data, the stoichiometry of Co(II) complex was found to be 1:2 (metal/ligand), but 1:1 for Ni(II). IR spectra indicate that the ligand acts as monoanionic NNO- tridentate and coordination takes place form through the oxime nitrogen, imine nitrogen, and enolate oxygen atoms.

Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies

NASA Astrophysics Data System (ADS)

Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

2017-08-01

Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH2-CH=CH-CH2-) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than 1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

Identification and Characterization of a Novel Class of c-Jun N-terminal Kinase Inhibitors

PubMed Central

Schepetkin, Igor A.; Kirpotina, Liliya N.; Khlebnikov, Andrei I.; Hanks, Tracey S.; Kochetkova, Irina; Pascual, David W.; Jutila, Mark A.

2012-01-01

In efforts to identify novel small molecules with anti-inflammatory properties, we discovered a unique series of tetracyclic indenoquinoxaline derivatives that inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 activation. Compound IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) was found to be a potent, noncytotoxic inhibitor of pro-inflammatory cytokine [interleukin (IL)-1α, IL-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon-γ, and granulocyte-macrophage colony-stimulating factor] and nitric oxide production by human and murine monocyte/macrophages. Three additional potent inhibitors of cytokine production were identified through further screening of IQ-1 analogs. The sodium salt of IQ-1 inhibited LPS-induced TNF-α and IL-6 production in MonoMac-6 cells with IC50 values of 0.25 and 0.61 μM, respectively. Screening of 131 protein kinases revealed that derivative IQ-3 [11H-indeno[1,2-b]quinoxalin-11-one-O-(2-furoyl)oxime]was a specific inhibitor of the c-Jun N-terminal kinase (JNK) family, with preference for JNK3. This compound, as well as IQ-1 and three additional oxime indenoquinoxalines, were found to be high-affinity JNK inhibitors with nanomolar binding affinity and ability to inhibit c-Jun phosphorylation. Furthermore, docking studies showed that hydrogen bonding interactions of the active indenoquinoxalines with Asn152, Gln155, and Met149 of JNK3 played an important role in enzyme binding activity. Finally, we showed that the sodium salt of IQ-1 had favorable pharmacokinetics and inhibited the ovalbumin-induced CD4+ T-cell immune response in a murine delayed-type hypersensitivity model in vivo. We conclude that compounds with an indenoquinoxaline nucleus can serve as specific small-molecule modulators for mechanistic studies of JNKs as well as a potential leads for the development of anti-inflammatory drugs. PMID:22434859

Oxime-Induced Reactivation and Efficacy against Lethality in Phosphinate-Intoxicated Guinea Pigs.

DTIC Science & Technology

1988-03-01

poisoning by pretreatment with a carbamate. Toxicol. Appl. Pharmacol., 43, 207-216. 5. Heyl, W. C., Harris, L. W., and Stitcher , D. L. (1978). Effects of...Lieske, C. N. (1984). Unpublished results. 12. Harris, L. W., Stitcher , D. L., Heyl, W. C., Lieske, C. N., Lowe, J. R., Clark, J. H., and Broomfield, C

77 FR 4225 - Oral Dosage Form New Animal Drugs; Milbemycin Oxime, Lufenuron, and Praziquantel

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

... control of fleas, and for the treatment and control of various internal parasites in dogs. DATES: This... and control of adult roundworm, adult hookworm, adult whipworm, and adult tapeworm infections in dogs...) Sponsor. See No. 058198 in Sec. 510.600(c) of this chapter. (c) [Reserved] (d) Conditions of use--(1) Dogs...

OZONE-SCAVENGING REAGENTS SUITABLE FOR USE IN THE QUANTITATIVE DETERMINATION OF ALDEHYDES AS THE O-(2,3,4,5,6-PENTAFLUOROBENZYL)OXIMES BY GC-ECD

EPA Science Inventory

Previously, we reported interference due to several ozone-scavenging reagents (OSRs) in the quantitation of aldehydes using 0-(2,3,4,5,6-pentafluorobenzyl)oxylamine (PFBOA) in the analysis of ozonated waters. Scavenging ozone is essential if ozonation byproduct concentrations ar...

Zirconium oxocluster/polymer hybrid nanoparticles prepared by photoactivated miniemulsion copolymerization

NASA Astrophysics Data System (ADS)

Benedetti, Cesare; Flouda, Paraskevi; Antonello, Alice; Rosenauer, Christine; Pérez-Pla, Francisco F.; Landfester, Katharina; Gross, Silvia; Muñoz-Espí, Rafael

2017-09-01

The photoactivated free radical miniemulsion copolymerization of methyl methacrylate (MMA) and the zirconium oxocluster Zr4O2(methacrylate)12 is used as an effective and fast preparation method for polymer/inorganic hybrid nanoparticles. The oxoclusters, covalently anchored to the polymer network, act as metal-organic cross-linkers, thus improving the thermomechanical properties of the resulting hybrid nanoparticles. Benzoin carbonyl organic compounds were used as photoinitiators. The obtained materials are compared in terms of cross-linking, effectiveness of cluster incorporation, and size distribution with the analogous nanoparticles produced by using conventional thermally induced free radical miniemulsion copolymerization. The kinetics of the polymerization process in the absence and in the presence of the oxocluster is also investigated.

The thermal stability of photoacid generators in phenolic matrices

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

Barclay, G.G.; Medeiros, D.R.; Sinta, R.F.

1993-12-31

The thermal stability of various photolabile sulfonate esters in phenolic matrices have been investigated by differential scanning calorimetry and thermogravimetric analysis. It was observed that the thermal stability of these photoacid generators is lowered in the presence of phenolic groups. As a result acid can be thermally generated, thereby reducing the selectivity of photoacid generation. The sulfonate esters investigated in phenolic matrices included nitrobenzyl tosylates, imino sulfonates, benzoin tosylate and 1,2,3-tris(methanesulfonyloxy)benzene. Also the effect of the thermal generation of acid from these photoacid generators on the temperature and rate of deprotection of partially t-butoxycarbonate blocked poly (vinylphenol) was studied bymore » thermogravimetric analysis and FTIR.« less

Photo-Induced Self-Condensation, A Technique For Fabricating Organic Lightguide Structures

NASA Astrophysics Data System (ADS)

Franke, H.; Heuer, W.

1986-11-01

Planar lightguides have been fabricated from mixtures of the polymer PMMA with benzoin type photoinitiators. Using conventional UV-photolithography 2 dimensional refractive index patterns were recorded in the polymer films. Thickness and refractive index of the organic lightguides were determined by m-line spectroscopy. The achieved refractive index changes increased with increasing photoinitiator concentrations. For high concentrations (< 70 %) the film refractive index could be increased via UV exposure by Δn = 0.03. Thermal treatment at below 100°C caused the out diffusion of the unexposed photoinitiator and completion of the photochemically induced reaction in the exposed parts of the film. Thus refractive index patterns (Δn < 0.05) could be developed and fixed.

Reaction between (Z)-arylchlorooximes and α-isocyanoacetamides: a procedure for the synthesis of aryl-α-ketoamide amides.

PubMed

Giustiniano, Mariateresa; Mercalli, Valentina; Cassese, Hilde; Di Maro, Salvatore; Galli, Ubaldina; Novellino, Ettore; Tron, Gian Cesare

2014-07-03

(Z)-Arylchlorooximes and α-isocyanoacetamides undergo a smooth reaction to produce 1,3-oxazol-2-oxime derivatives in good yields. Opening of the oxazole ring and deoximation reaction give a facile access to aryl-α-ketoamide amides, a class of privileged scaffolds in medicinal chemistry and important synthetic intermediates in organic chemistry.

Physiological Feedback Control 2011-2012 Annual Report

DTIC Science & Technology

2013-01-07

Invention Title: UM 3709 – Dendrimeric Prodrug as a Controlled Release Formulation in Pain Management – Patent Title: Dendrimer Conjugates Patent... Dendrimeric Prodrug as a Controlled Release Formulation in Pain Management – Patent Title: Dendrimer Conjugates Patent/Application Numbers: 61/101,461; 12...class of dendrimer -oxime drug conjugates, and evaluated the mechanism by which these conjugates hydrolyze paraoxon. (a) Papers published in peer

RESEARCH NOTE: INTERFERENCES DUE TO OZONE-SCAVENGING REAGENTS IN THE GC-ECD DETERMINATION OF ALDEHYDES AND KETONS AS THE O-(2,3,4,5,6-PENTAFLUOROBENZYL)OXIMES

EPA Science Inventory

Six potential ozone-scavenging reagents were tested for possible interference in the GC-ECD determination of aldehydes and ketones after derivatization with O-(2,3,4,5,6-pentafluorobenzyl)oxylamine (PFBOA). All six-nitrite, cynaide, methanoate (formate), indigo-55'-disulfonate d...

Lipophilicity indices derived from the liquid chromatographic behavior observed under bimodal retention conditions (reversed phase/hydrophilic interaction): application to a representative set of pyridinium oximes.

PubMed

Voicu, Victor; Sârbu, Costel; Tache, Florentin; Micăle, Florina; Rădulescu, Ştefan Flavian; Sakurada, Koichi; Ohta, Hikoto; Medvedovici, Andrei

2014-05-01

The liquid chromatographic behavior observed under bimodal retention conditions (reversed phase and hydrophilic interaction) offers a new basis for the determination of some derived lipophilicity indices. The experiments were carried out on a representative group (30 compounds) of pyridinium oximes, therapeutically tested in acetylcholinesterase reactivation, covering a large range of lipophilic character. The chromatographic behavior was observed on a mixed mode acting stationary phase, resulting from covalent functionalization of high purity spherical silica with long chain alkyl groups terminated by a polar environment created through the vicinal diol substitution at the lasting carbon atoms (Acclaim Mixed Mode HILIC 1 column). Elution was achieved by combining different proportions of 5 mM ammonium formiate solutions in water and acetonitrile. The derived lipophilicity indices were compared with logP values resulting from different computational algorithms. The correlations between experimental and computed data sets are significant. To obtain a better insight on the transition from reversed phase to hydrophilic interaction retention mechanisms, the variation of the thermodynamic parameters determined through the van׳t Hoff approach was also discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Montmorillonite Functionalized with Pralidoxime as a Material for Chemical Protection against Organophosphorous Compounds

DTIC Science & Technology

2011-03-25

implied is via iondipole forces.5,6 It is well-known that clays such as montmorillonite and kaolinite accelerate the degradation of insecticides such...REPORT Montmorillonite Functionalized with Pralidoxime As a Material for Chemical Protection against Organophosphorous Compounds 14. ABSTRACT 16...SECURITY CLASSIFICATION OF: Montmorillonite K-10 functionalized with ?-nucleophilic 2-pralidoxime (PAM) and its zwitterionic oximate form (PAMNa) is

Bridged Bicyclic Oximes as Acetylcholinesterase Reactivators

DTIC Science & Technology

1988-04-03

with acetylcholine as substrate, is based on coupling away the choline produced from the esterase reaction with choline kinase, which catalyzes the...transfer of the y-phosphate from ATP to choline , producing ADP, and then removed with the pyruvate kinase-lactate dehydrogenase couple, and disappearance...nitrobenzoic acid absorbs strongly at 412 nm. Choline kinase and acetylcholinesterase were purchased from Sigma as the lyophilized powders. Each enzyme

Characterization of Soman Toxicity in Atropine and Oxime (HI-6 and MMB- 4) Treated Rhesus Monkeys

DTIC Science & Technology

1991-03-30

observation period in which a;ni:als died minus the onset time for nonsurvivors. S ). 1 31 .4w~ ~ -.. -- - ’-0 4 .4W .,- aai Iw CA 0 Q C) z ൰ a -’. - -L...Animal Care and Use Comitte ( IACUC ) prior to initiation of the study. The Program Oirector accepts responsibility for the proper care and use of

Paradoxical vestibular syndrome in a dog from western Newfoundland infected with French heartworm (Angiostrongylus vasorum)

PubMed Central

Jang, Hye-Yeon; Parent, Joane M.; Hagen, Chris; Colwell, Emily; Rist, Paul M.; Murphy, Nicole; Burton, Shelley; Conboy, Gary

2016-01-01

A dog from western Newfoundland was presented with paradoxical vestibular syndrome. First-stage larvae of Angiostrongylus vasorum were detected on fecal examination. Treatment with milbemycin oxime resulted in resolution of signs. This is the first report of the spread of this parasite to western Newfoundland and of paradoxical vestibular syndrome in a dog infected with A. vasorum. PMID:27928171

Toxic Industrial Chemicals: A Future Weapons of Mass Destruction Threat

DTIC Science & Technology

2002-05-31

1937 by Dr. Gerhard Schrader, a chemist conducting insecticide research with organophosphates (Stockholm International Peace Research Institute 1971...International Peace Research Institute 1971 and 1973). Phosgene oxime is known as “ nettle gas,” so named because of its property of intensely irritating...as a WMD. Common TICs Effects of CW Agents Organophosphate Insecticide Nerve Dimethyl Sulfate Blister Methyl Isocyanate Blood Anhydrous Ammonia

Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies.

PubMed

Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

2017-08-01

Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH 2 -CH=CH-CH 2 -) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than ~1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

Evaluation of the coordination preferences and catalytic pathways of heteroaxial cobalt oximes towards hydrogen generation

DOE PAGES

Basu, Debashis; Mazumder, Shivnath; Niklas, Jens; ...

2016-02-02

Three new heteroaxial cobalt oxime catalysts, namely [Co III(prdioxH)( 4tBupy)(Cl)]PF 6 (1), [Co III(prdioxH)( 4Pyrpy)(Cl)]PF 6 (2), and [Co III(prdioxH)( 4Bzpy)(Cl)]PF 6 (3) have been studied. These species contain chloro and substituted tert-butyl/pyrrolidine/benzoyl-pyridino ligands axially coordinated to a trivalent cobalt ion bound to the N 4-oxime macrocycle (2 E,2' E,3 E,3' E)-3,3'-(propane-1,3-diylbis(azanylylidene))bis(butan-2-one)dioxime, abbreviated (prdioxH)– in its monoprotonated form. Emphasis was given to the spectroscopic investigation of the coordination preferences and spin configurations among the different 3d 6 Co III, 3d 7 Co II, and 3d 8 Co I oxidation states of the metal, and to the catalytic proton reduction withmore » an evaluation of the pathways for the generation of H 2 via Co III–H – or Co II–H – intermediates by mono and bimetallic routes. The strong field imposed by the (prdioxH)– ligand precludes the existence of high-spin configurations, and 6-coordinate geometry is favored by the LSCo III species. Species 1 and 3 show a split Co III/Co II electrochemical wave associated with partial chemical conversion to a [Co III(prdioxH)Cl 2] species, whereas 2 shows a single event. The reduction of these Co III complexes yields LSCo II and LSCo I species in which the pyridine acts as the dominant axial ligand. In the presence of protons, the catalytically active Co I species generates a Co III–H – hydride species that reacts heterolytically with another proton to generate dihydrogen. The intermediacy of a trifluoroacetate-bound Co III/Co II couple in the catalytic mechanism is proposed. Finally, these results allow for a generalization of the behavior of heteroaxial cobalt macrocycles and serve as guidelines for the development of new catalysts based on macrocyclic frameworks.« less

Quaternary and tertiary aldoxime antidotes for organophosphate exposure in a zebrafish model system

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

Schmidt, Hayden R.; Radić, Zoran; Taylor, Palmer

The zebrafish is rapidly becoming an important model system for screening of new therapeutics. Here we evaluated the zebrafish as a potential pharmacological model for screening novel oxime antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE). The k{sub i} values determined for chlorpyrifos oxon (CPO) and dichlorvos (DDVP) showed that CPO was a more potent inhibitor of both human and zebrafish AChE, but overall zebrafish AChE was less sensitive to OP inhibition. In contrast, aldoxime antidotes, the quaternary ammonium 2-PAM and tertiary amine RS-194B, showed generally similar overall reactivation kinetics, k{sub r}, in both zebrafish and human AChE. However, differences between themore » K{sub ox} and k{sub 2} constants suggest that zebrafish AChE associates more tightly with oximes, but has a slower maximal reactivation rate than human AChE. Homology modeling suggests that these kinetic differences result from divergences in the amino acids lining the entrance to the active site gorge. Although 2-PAM had the more favorable in vitro reactivation kinetics, RS-194B was more effective antidote in vivo. In intact zebrafish embryos, antidotal treatment with RS-194B rescued embryos from OP toxicity, whereas 2-PAM had no effect. Dechorionation of the embryos prior to antidotal treatment allowed both 2-PAM and RS-194B to rescue zebrafish embryos from OP toxicity. Interestingly, RS-194B and 2-PAM alone increased cholinergic motor activity in dechorionated embryos possibly due to the reversible inhibition kinetics, K{sub i} and αK{sub i}, of the oximes. Together these results demonstrate that the zebrafish at various developmental stages provides an excellent model for investigating membrane penetrant antidotes to OP exposure. - Highlights: • Zebrafish AChE shares significant structural similarities with human AChE. • OP-inhibited zebrafish and human AChE exhibit similar reactivation kinetics. • The zebrafish chorion is permeable to BBB penetrant and not charged aldoximes. • Zebrafish are a good aquatic model for studying centrally acting antidotes.« less

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

Mishra, Ashutosh; Dwivedi, Jagrati, E-mail: hemu.dwi@gmail.com; Shukla, Kritika

Five Chromium (III) complexes have been prepared using Schiff base ligands which derived from benzoin and five different amino acids (H{sub 2}N-R). Samples were characterized by XRD, FTIR, UV-VIS and SEM method. X-Ray diffraction pattern analyzed that all chromium (III) complexes have hexagonal structure and crystalline, in nature, using Bruker D8 Advance instrument. Using VERTAX 70, FTIR spectroscopy reveals that Samples have (C=N), (C-O), (M-N) and (M-O) bonds in the range of 4000-400cm{sup −1}. UV-VIS spectroscopy give information that samples absorb the visible light which is in the range of 380-780nm. For this, Lambda 960 spectrometer used. SEM is designedmore » for studying of the solid objects, using JEOL JSM 5600 instrument.« less

A Continuum of Progress: Applications of N-Hetereocyclic Carbene Catalysis in Total Synthesis

PubMed Central

Izquierdo, Javier; Hutson, Gerri E.; Cohen, Daniel T.; Scheidt, Karl A.

2013-01-01

N-Heterocyclic carbene (NHC) catalyzed transformations have emerged as powerful tactics for the construction of complex molecules. Since Stetter’s report in 1975 of the total synthesis of cis-jasmon and dihydrojasmon by using carbene catalysis, the use of NHCs in total synthesis has grown rapidly, particularly over the last decade. This renaissance is undoubtedly due to the recent developments in NHC-catalyzed reactions, including new benzoin, Stetter, homoenolate, and aroylation processes. These transformations employ typical as well as Umpolung types of bond disconnections and have served as the key step in several new total syntheses. This Minireview highlights these reports and captures the excitement and emerging synthetic utility of carbene catalysis in total synthesis. PMID:23074146

Benzoin 4-ethylthiosemicarbazone.

PubMed

Dinçer, Muharrem; Ozdemir, Namik; Cukurovali, Alaaddin; Yilmaz, Ibrahim; Büyükgüngör, Orhan

2006-01-01

In the title compound, 2-hydroxy-1,2-diphenylethanone 4-ethylthiosemicarbazone, C17H19N3OS, the thiosemicarbazone moiety is planar and has an E configuration. The planar phenyl rings make dihedral angles of 82.34 (8) and 8.07 (17) degrees with the plane of the thiosemicarbazone moiety. The crystal structure contains two intramolecular (N-H...O and N-H...N) and one intermolecular interaction (O-H...S), as well as two C-H...pi(benzene) interactions. Molecules are stacked in columns running along the a axis. Molecules in each column are connected to each other by means of linear O-H...S hydrogen bonds and C-H...pi interactions. In addition, there are also C-H...pi(benzene) interactions between the columns.

Efficient white light generation from 2,3-diphenyl-1,2-dihydro-quinoxaline complex

NASA Astrophysics Data System (ADS)

Dwivedi, Y.; Kant, S.; Rai, R. N.; Rai, S. B.

2010-11-01

In this article, we report two organic materials dispersed in transparent poly (methyl methacrylate) matrix for efficient white light simulation under different optical excitations. A newly synthesized complex of benzoin and o-phenyldiamine is observed to be white on illumination with a blue LED. A new concept of white light emitting tube is also demonstrated. A mixture of 2,2″-([1,1'-biphenyl]-4,4'-diyldi-2,1-ethenediyl)-bis-benzenesulfonic acid disodium salt and complex is optimized to emit white light extended in the violet region on 355 nm laser excitation. The optical quality of the emitted white light is adjudged by the CIE coordinate, correlated color temperature and color rendition index in both the cases.

JPRS Report. Science & Technology: China.

DTIC Science & Technology

1989-05-16

Nine aminothiazo peniciliate derivatives were synthesized and their antibacterial activities were tested. The following is the basic structure of the...Ph)tCNNH, » (PhhCN, NHr / S\\/ v 6—APA \\ 4 -N VIII Or XCOOCHPh, Route of Synthesis In Vitro Antibacterial Activities of Compound VIIi_8...Lactam Antibiotics. VII. Effect on Antibacterial Activity of the Oxime O-Substituents with Various Functional Groups in the 7 3-(Z-2-(2-Amino-4

Cholinesterase Structure: Identification of Mechanisms and Residues Involved in Organophosphate Inhibition and Enzyme Reactivation

DTIC Science & Technology

2005-05-01

nerve agents , soman is the great- terrorist acts. At the same time, OP pesticides , such as est challenge since both the rapid aging of the soman- paraoxon...also from enzyme very slowly (requiring hours, days, or weeks used as nerve warfare agents . Similar to pesticides , nerve for complete dissociation...TERMS acetylcholinesterase, nerve agent antidotes and propylaxis, organophosphate scavenging , oxime reactivation fluorescence spectroscopy, exposure

Present State of CBRN Decontamination Methodologies (Stand van Zaken CBRN- Ontsmettingsmethodieken)

DTIC Science & Technology

2007-03-01

activity and effectiveness . The oxidation of HD requires the presence of activators such as carbonate (CO 3 2-, bicarbonate (HC0 3") or molybdate (MOO 4 2...gasses), nucleophilic substitution (alkaline hydrolysis and oximes) and alternative chemical approaches. Some chemical decontaminants are effective ...are commercially available. Most enzymes are only effective against GB and GD, however, some enzymatic approaches towards destruction of VX, HD and

Identification and Characterization of Novel Catalytic Bioscavengers of Organophosphorus Nerve Agents

DTIC Science & Technology

2013-01-01

hydrolase activity . These strains are Ammoniphilus oxalaticus, Haloarcula sp., and Micromonospora aurantiaca. Lysates from A. oxalaticus had...warfare agents [1–3]. OP nerve agents readily bind covalently to the active site serine in acetylcho- linesterase (AChE), thereby inhibiting the ability...muscarinic receptors, whereas 2-pralidoxime chloride, an oxime nucleophile, reactivates AChE by displacing the phospho- nyl group left on the active site

INFLUENCES OF METAL CATIONS ON THE DETERMINATION OF THE A-OXOCARBOXYLATES AS THE METHYL ESTERS OF THE O-(2,3,4,5,6-PENTAFLUOROBENZYL)OXIMES BY GAS CHROMATOGRAPHY: THE IMPORTANCE OF ACCOUNTING FOR MATRIX EFFECTS

EPA Science Inventory

The a-oxocarboxylates (a-ketocarboxylates) and the corresponding a-oxoacids (a-ketoacids) have been reported as byproducts of ozonation of potable water supplies. In this analytical method, the oxo moiety is derivatized with O-(2,3,4,5,6-pentafluorobenzyl)-oxylamine (PFBOA) for f...

Synthesis of Laser Dyes

DTIC Science & Technology

1988-11-09

with m.ethoxy groups- on the Three aninoketone hydrochlorides derived From 1 -indanorles have been prepared. These are 2-amino-i- indanone , 3, 3-dimethiyl... indanone , was commercially available. The substituted 1 - indanones for preparation of VIb and VJc were prepared by addition of phenylmagnesium bromide...dimethyl-l- indanone by heating with polyphosphoric acid.7 The 1 - indanones were all converted to the 2-oximes by reaction with butyl nitrite under acid

One Hundred Eighty Day Subchronic Oral Toxicity Study of Pyridostigmine Bromide in Rats. Volume 1

DTIC Science & Technology

1990-06-01

has proposed a treatment regimen incorporating prophylaxis with a reversible cholinesterase inhibitor and, following nerve agent exposure, antidotal...would accomplish two goals: the oxime would abate the inhibition induced by the reversible cholinesterase inhibitor prophylaxis, and the atropine will...cholinesterase inhibitor as the pretreatment component of a therapeutic regimen that would include antidotal therapy with 2-PAM chloride and atropine. A

Rapid End-Group Modification of Polysaccharides for Biomaterial Applications in Regenerative Medicine.

PubMed

Bondalapati, Somasekhar; Ruvinov, Emil; Kryukov, Olga; Cohen, Smadar; Brik, Ashraf

2014-09-15

Polysaccharides have emerged as important functional materials because of their unique properties such as biocompatibility, biodegradability, and availability of reactive sites for chemical modifications to optimize their properties. The overwhelming majority of the methods to modify polysaccharides employ random chemical modifications, which often improve certain properties while compromising others. On the other hand, the employed methods for selective modifications often require excess of coupling partners, long reaction times and are limited in their scope and wide applicability. To circumvent these drawbacks, aniline-catalyzed oxime formation is developed for selective modification of a variety of polysaccharides through their reducing end. Notably, it is found that for efficient oxime formation, different conditions are required depending on the composition of the specific polysaccharide. It is also shown how our strategy can be applied to improve the physical and functional properties of alginate hydrogels, which are widely used in tissue engineering and regenerative medicine applications. While the randomly and selectively modified alginate exhibits similar viscoelastic properties, the latter forms significantly more stable hydrogel and superior cell adhesive and functional properties. Our results show that the developed conjugation reaction is robust and should open new opportunities for preparing polysaccharide-based functional materials with unique properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage-Preparation, in vitro screening and molecular docking.

PubMed

Musilek, Kamil; Komloova, Marketa; Holas, Ondrej; Horova, Anna; Pohanka, Miroslav; Gunn-Moore, Frank; Dohnal, Vlastimil; Dolezal, Martin; Kuca, Kamil

2011-01-15

The treatment of organophosphorus (OP) poisoning consists of the administration of a parasympatholytic agent (e.g., atropine), an anticonvulsant (e.g., diazepam) and an acetylcholinesterase (AChE) reactivator (e.g., obidoxime). The AChE reactivator is the causal treatment of OP exposure, because it cleaves the OP moiety covalently bound to the AChE active site. In this paper, fourteen novel AChE reactivators are described. Their design originated from a former promising compound K027. These compounds were synthesized, evaluated in vitro on human AChE (hAChE) inhibited by tabun, paraoxon, methylparaoxon and DFP and then compared to commercial hAChE reactivators (pralidoxime, HI-6, trimedoxime, obidoxime, methoxime) or previously prepared compounds (K027, K203). Three of these novel compounds showed a promising ability to reactivate hAChE comparable or better than the used standards. Consequently, a molecular docking study was performed for three of these promising novel compounds. The docking results confirmed the apparent influence of π-π or cation-π interactions and hydrogen bonding for reactivator binding within the hAChE active site cleft. The SAR features concerning the non-oxime part of the reactivator molecule are also discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

Determination of Carbonyl Groups in Pyrolysis Bio-oils Using Potentiometric Titration: Review and Comparison of Methods

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

Black, Stuart; Ferrell, Jack R.

Carbonyl compounds present in bio-oils are known to be responsible for bio-oil property changes upon storage and during upgrading. As such, carbonyl content has previously been used as a method of tracking bio-oil aging and condensation reactions with less variability than viscosity measurements. Given the importance of carbonyls in bio-oils, accurate analytical methods for their quantification are very important for the bio-oil community. Potentiometric titration methods based on carbonyl oximation have long been used for the determination of carbonyl content in pyrolysis bio-oils. Here in this study, we present a modification of the traditional carbonyl oximation procedures that results inmore » less reaction time, smaller sample size, higher precision, and more accurate carbonyl determinations. Some compounds such as carbohydrates are not measured by the traditional method (modified Nicolaides method), resulting in low estimations of the carbonyl content. Furthermore, we have shown that reaction completion for the traditional method can take up to 300 hours. The new method presented here (the modified Faix method) reduces the reaction time to 2 hours, uses triethanolamine (TEA) in the place of pyridine, and requires a smaller sample size for the analysis. Carbonyl contents determined using this new method are consistently higher than when using the traditional titration methods.« less

Kinetic analysis of inhibition of glucoamylase and active site mutants via chemoselective oxime immobilization of acarbose on SPR chip surfaces.

PubMed

Sauer, Jørgen; Abou Hachem, Maher; Svensson, Birte; Jensen, Knud J; Thygesen, Mikkel B

2013-06-28

We here report a quantitative study on the binding kinetics of inhibition of the enzyme glucoamylase and how individual active site amino acid mutations influence kinetics. To address this challenge, we have developed a fast and efficient method for anchoring native acarbose to gold chip surfaces for surface plasmon resonance studies employing wild type glucoamylase and active site mutants, Y175F, E180Q, and R54L, as analytes. The key method was the chemoselective and protecting group-free oxime functionalization of the pseudo-tetrasaccharide-based inhibitor acarbose. By using this technique we have shown that at pH 7.0 the association and dissociation rate constants for the acarbose-glucoamylase interaction are 10(4)M(-1)s(-1) and 10(3)s(-1), respectively, and that the conformational change to a tight enzyme-inhibitor complex affects the dissociation rate constant by a factor of 10(2)s(-1). Additionally, the acarbose-presenting SPR surfaces could be used as a glucoamylase sensor that allowed rapid, label-free affinity screening of small carbohydrate-based inhibitors in solution, which is otherwise difficult with immobilized enzymes or other proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis, X-ray Single Crystal Structure, Molecular Docking and DFT Computations on N-[(1E)-1-(2H-1,3-Benzodioxol-5-yl)-3-(1H-imidazol-1-yl)propylidene]-hydroxylamine: A New Potential Antifungal Agent Precursor.

PubMed

Al-Wabli, Reem I; Al-Ghamdi, Alwah R; Ghabbour, Hazem A; Al-Agamy, Mohamed H; Monicka, James Clemy; Joe, Issac Hubert; Attia, Mohamed I

2017-02-28

Mycoses are serious health problem, especially in immunocompromised individuals. A new imidazole-bearing compound containing an oxime functionality was synthesized and characterized with different spectroscopic techniques to be used for the preparation of new antifungal agents. The stereochemistry of the oxime double bond was unequivocally determined via the single crystal X-ray technique. The title compound 4 , C 13 H 13 N₃O₃·C₃H₈O, crystallizes in the monoclinic space group P 2₁with a = 9.0963(3) Å, b = 14.7244(6) Å, c = 10.7035(4) Å, β = 94.298 (3)°, V = 1429.57(9) ų, Z = 2. The molecules were packed in the crystal structure by eight intermolecular hydrogen bond interactions. A comprehensive spectral analysis of the title molecule 4 has been performed based on the scaled quantum mechanical (SQM) force field obtained by density-functional theory (DFT) calculations. A molecular docking study illustrated the binding mode of the title compound 4 into its target protein. The preliminary antifungal activity of the title compound 4 was determined using a broth microdilution assay.

Butyrylcholinesterase for protection from organophosphorus poisons; catalytic complexities and hysteretic behavior

PubMed Central

Masson, Patrick; Lockridge, Oksana

2009-01-01

Butyrylcholinesterase is a promiscuous enzyme that displays complex kinetic behavior. It is toxicologically important because it detoxifies organophosphorus poisons (OP) by making a covalent bond with the OP. The OP and the butyrylcholinesterase are both inactivated in the process. Inactivation of butyrylcholinesterase has no adverse effects. However inactivation of acetylcholinesterase in nerve synapses can be lethal. OP-inhibited butyrylcholinesterase and acetylcholinesterase can be reactivated with oximes provided the OP has not aged. Strategies for preventing the toxicity of OP include a) treatment with an OP scavenger, b) reaction of nonaged enzyme with oximes, c) reactivation of aged enzyme, d) slowing down aging with peripheral site ligands, and e) design of mutants that rapidly hydrolyze OP. Option (a) has progressed through phase I clinical trials with human butyrylcholinesterase. Option (b) is in routine clinical use. The others are at the basic research level. Butyrylcholinesterase displays complex kinetic behavior including activation by positively charged esters, ability to hydrolyze amides, and a lag time (hysteresis) preceding hydrolysis of benzoylcholine and N-methyl indoxyl acetate. Mass spectrometry has identified new OP binding motifs on tyrosine and lysine in proteins that have no active site serine. It is proposed, but not yet proven, that low dose exposure involves OP modification of proteins that have no active site serine. PMID:20004171

Dynamic Mechanism of a Fluorinated Oxime Reactivator Unbinding from AChE Gorge in Polarizable Water.

PubMed

Pathak, Arup K; Bandyopadhyay, Tusar

2018-04-12

A well-tempered metadynamics simulation is performed to study the unbinding process of a fluorinated oxime (FHI-6) drug from the active-site gorge of acetylcholinesterase enzyme in a polarizable water medium. Cation-π interactions and water bridge and hydrogen bridge formations between the protein and the drug molecule are found to strongly influence the unbinding process, forming basins and barriers along the gorge pathway. Distinct unbinding pathways are found when FHI-6 was compared with its recently reported nonfluorinated analogue, HI-6. For example, because of permanent positive charges on both the pyridinium rings of HI-6, it exhibits the minimum in the potential of mean force of the unbinding process in the gorge mouth (where the peripheral anion site, PAS, of the enzyme is located), which is largely caused by cation-π interactions. However, the same interaction, both in the catalytic active-site (CAS) and PAS regions, is found to be greatly enhanced in its lipophilic fluorinated analogue, FHI-6, causing a deep potential energy minimum in the bound state. This may render FHI-6 to be held more firmly in the CAS region of the gorge, as is also evidenced from the microkinetics of unbinding transitions, measured through a combination of metadynamics and hyperdynamics simulations.

Determination of Carbonyl Groups in Pyrolysis Bio-oils Using Potentiometric Titration: Review and Comparison of Methods

DOE PAGES

Black, Stuart; Ferrell, Jack R.

2016-01-06

Carbonyl compounds present in bio-oils are known to be responsible for bio-oil property changes upon storage and during upgrading. As such, carbonyl content has previously been used as a method of tracking bio-oil aging and condensation reactions with less variability than viscosity measurements. Given the importance of carbonyls in bio-oils, accurate analytical methods for their quantification are very important for the bio-oil community. Potentiometric titration methods based on carbonyl oximation have long been used for the determination of carbonyl content in pyrolysis bio-oils. Here in this study, we present a modification of the traditional carbonyl oximation procedures that results inmore » less reaction time, smaller sample size, higher precision, and more accurate carbonyl determinations. Some compounds such as carbohydrates are not measured by the traditional method (modified Nicolaides method), resulting in low estimations of the carbonyl content. Furthermore, we have shown that reaction completion for the traditional method can take up to 300 hours. The new method presented here (the modified Faix method) reduces the reaction time to 2 hours, uses triethanolamine (TEA) in the place of pyridine, and requires a smaller sample size for the analysis. Carbonyl contents determined using this new method are consistently higher than when using the traditional titration methods.« less

Bioscavengers for the protection of humans against organophosphate toxicity.

PubMed

Doctor, Bhupendra P; Saxena, Ashima

2005-12-15

Current antidotes for organophosphorus compounds (OP) poisoning consist of a combination of pretreatment with carbamates (pyridostigmine bromide), to protect acetylcholinesterase (AChE) from irreversible inhibition by OP compounds, and post-exposure therapy with anti-cholinergic drugs (atropine sulfate) to counteract the effects of excess acetylcholine and oximes (e.g., 2-PAM chloride) to reactivate OP-inhibited AChE. These antidotes are effective in preventing lethality from OP poisoning, but they do not prevent post-exposure incapacitation, convulsions, seizures, performance decrements, or in many cases permanent brain damage. These symptoms are commonly observed in experimental animals and are likely to occur in humans. The problems intrinsic to these antidotes stimulated attempts to develop a single protective drug, itself devoid of pharmacological effects, which would provide protection against the lethality of OP compounds and prevent post-exposure incapacitation. One approach is the use of enzymes such as cholinesterases (ChEs), beta-esterases in general, as single pretreatment drugs to sequester highly toxic OP anti-ChEs before they reach their physiological targets. This approach turns the irreversible nature of the OP: ChE interaction from disadvantage to an advantage; instead of focusing on OP as an anti-ChE, one can use ChE as an anti-OP. Using this approach, it was shown that administration of fetal bovine serum AChE (FBSAChE) or equine serum butyrylcholinesterase (EqBChE) or human serum BChE (HuBChE) protected the animals from multiple LD50s of a variety of highly toxic OPs without any toxic effects or performance decrements. The bioscavengers that have been explored to date for the detoxification of OPs fall into three categories: (A) those that can catalytically hydrolyze OPs and thus render them non-toxic, such as OP hydrolase and OP anhydrase; (B) those that stoichiometrically bind to OPs, that is, 1 mol of enzyme neutralizes one or 2 mol of OP inactivating both, such as ChEs and related enzymes; and (C) and those generally termed as "pseudo catalytic", e.g., a combination of ChE and an oxime pre-treatment such that the catalytic activity of OP-inhibited ChE can rapidly and continuously be restored in the presence of an oxime. Since the biochemical mechanism underlying prophylaxis by exogenous esterases such as ChEs is established and tested in several animal species, including non-human primates, this concept should allow a reliable extrapolation of results from animal experiments to human application. Having being extensively investigated by several groups, plasma derived HuBChE is judged to be the most suitable bioscavenger for its advancement for human use. The program is being developed at the present time for conducting a safety clinical trial in human volunteers. Several other candidate bioscavengers will follow; e.g., recombinant HuBChE expressed in the milk of transgenic goats, pseudo catalytic scavenger(s), e.g., a combination of ChE and oxime, and possibly PON 1 as a catalytic scavenger in the future.

Breslow Intermediates from Aromatic N-Heterocyclic Carbenes (Benzimidazolin-2-ylidenes, Thiazolin-2-ylidenes).

PubMed

Berkessel, Albrecht; Paul, Mathias; Sudkaow, Panyapon; Wessels, Alina; Schlörer, Nils E; Neudörfl, Jörg M

2018-04-12

We report the first generation and characterization of the elusive Breslow intermediates derived from aromatic N-heterocyclic carbenes (NHCs), namely benzimidazolin-2-ylidenes (NMR, X-ray) and thiazolin-2-ylidenes (NMR). In the former case, the diaminoenols were generated by reaction of the free N,N-bis-Dipp- and N,N-bis-Mes-benzimidazolin-2-ylidenes with aldehydes, while the dimer of 3,4,5-trimethylthiazolin-2-ylidene served as the starting material in the latter case. The unambiguous NMR-identification of the first thiazolin-2-ylidene based Breslow intermediate rests on double 13C labeling of both the NHC and the aldehyde component. Acyl anion reactivity was proven by benzoin formation with excess aldehyde. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stereoselective reduction of aromatic ketones by a new ketoreductase from Pichia glucozyma.

PubMed

Contente, Martina Letizia; Serra, Immacolata; Brambilla, Marta; Eberini, Ivano; Gianazza, Elisabetta; De Vitis, Valerio; Molinari, Francesco; Zambelli, Paolo; Romano, Diego

2016-01-01

A new NADPH-dependent benzil reductase (KRED1-Pglu) was identified from the genome of the non-conventional yeast Pichia glucozyma CBS 5766 and overexpressed in E. coli. The new protein was characterised and reaction parameters were optimised for the enantioselective reduction of benzil to (S)-benzoin. A thorough study of the substrate range of KRED1-Pglu was conducted; in contrast to most other known ketoreductases, KRED1-Pglu prefers space-demanding substrates, which are often converted with high stereoselectivity. A molecular modelling study was carried out for understanding the structural determinants involved in the stereorecognition experimentally observed and unpredictable on the basis of steric properties of the substrates. As a result, a new useful catalyst was identified, enabling the enantioselective preparation of different aromatic alcohols and hydroxyketones.

Radiation polymerisable compositions containing 3-sorboyloxy-2-hydroxypropyl groups

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

Green, G.E.

1976-02-03

Compounds having at least three 3-sorboyloxy-2-hydroxypropyl groups directly attached to ether oxygen atoms are polymerised by exposure to actinic radiation, preferably in the presence of a sensitizer such as Michler's ketone or benzoin. The compounds may be obtained by the reaction either of sorbic acid with a substance having at least three glycidyl ether groups or of glycidyl sorbate with a substance having at least three phenolic or alcoholic hydroxyl groups: if desired, not all of the glycidyl groups may be consumed, so that, after actinically induced polymerisation, the epoxide-containing polymer may be cross-linked by reaction with a curing agentmore » for epoxide resins. The compounds are useful in making printed circuits or printing plates for offset printing.« less

Complex formation of vanadium(V) with resorcylalhydrazides of carboxylic acids

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

Dudarev, V.I.; Dolgorev, V.A.; Volkov, A.N.

1986-08-01

In this work, a previous investigation of hydrazine derivatives as analytical reagents for vanadium(V) was continued. The authors studied arylalhydrazones -- derivatives of resorcylalhydrazides of anisic (RHASA), anthranilic (RHANA), and benzoic (RHBA) acids. The reagents presented differ from those studied previously by the presence of a second hydroxy group in the para-position of the benzene ring -the resorcinol fragment -- and substituents in the benzoin fragment. Such changes made it possible to increase the solubility of the reagents in aqueous medium and to estimate the change in the main spectrophotometric parameters of the analytical reaction. A rapid method was developedmore » for the determination of vanadium in steels with the resorcylalhydrazide of anthranilic acid. The minimum determinable vanadium content is 0.18 micrograms/ml.« less

Active-Site Engineering of Benzaldehyde Lyase Shows That a Point Mutation Can Confer Both New Reactivity and Susceptibility to Mechanism-Based Inhibition

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

Brandt, Gabriel S.; Kneen, Malea M.; Petsko, Gregory A.

2010-02-11

Benzaldehyde lyase (BAL) from Pseudomonas putida is a thiamin diphosphate (ThDP)-dependent enzyme that catalyzes the breakdown of (R)-benzoin. Here we report that a point mutant, BAL A28S, not only catalyzes the decarboxylation of benzoylformate but, like benzoylformate decarboxylase (BFDC), is also inactivated by the benzoylformate analogues methyl benzoylphosphonate (MBP) and benzoylphosphonate (BP). The latter has no effect on wild-type BAL, and the inactivation of the A28S variant is shown to result from phosphorylation of the newly introduced serine residue. This lends support to the proposal that an appropriately placed nucleophile facilitates the expulsion of carbon dioxide from the active sitemore » in many ThDP-dependent decarboxylases.« less

X-ray diffraction, FTIR, UV-VIS and SEM studies on chromium (III) complexes

NASA Astrophysics Data System (ADS)

Mishra, Ashutosh; Dwivedi, Jagrati; Shukla, Kritika

2015-06-01

Five Chromium (III) complexes have been prepared using Schiff base ligands which derived from benzoin and five different amino acids (H2N-R). Samples were characterized by XRD, FTIR, UV-VIS and SEM method. X-Ray diffraction pattern analyzed that all chromium (III) complexes have hexagonal structure and crystalline, in nature, using Bruker D8 Advance instrument. Using VERTAX 70, FTIR spectroscopy reveals that Samples have (C=N), (C-O), (M-N) and (M-O) bonds in the range of 4000-400cm-1. UV-VIS spectroscopy give information that samples absorb the visible light which is in the range of 380-780nm. For this, Lambda 960 spectrometer used. SEM is designed for studying of the solid objects, using JEOL JSM 5600 instrument.

A Liquid Chromatographic-Mass Spectrometric (LC-MS) Method for the Analysis of the Bis-pyridinium Oxime ICD-585 in Plasma: Application in a Guinea Pig Model

DTIC Science & Technology

2010-01-01

Chrom LC –MS...Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE A liquid chromatographic–mass spectrometric ( LC –MS) method for the analysis of the 5a...Journal of Chromatography B journa l homepage: www.e lsev ier .com/ locate /chromb A liquid chromatographic–mass spectrometric ( LC –MS) method for

The Design, Synthesis and Screening of Potential Pyridinium Oxime Prodrugs

DTIC Science & Technology

1984-02-01

In vitro and in vivo ( mice ) screening of these compounds indicates some promise as AChE regenerators, prompting the preparation of gram quantities of...PAM 6 (E-I) have been synthesized and characterized. In vitro (immobilized-AChE) and in vivo ( mice ) screening of these compounds showed promising...screening assay. An ED5 0 determination (diisopropylfluorophosphate [DFPJ challenge/ mice ) showed 5-I-2-PAM (5) to be significantly more effective than 2

The Mechanism of Interaction of Oximes with the Muscarinic-Cholinergic Complex in the Central Nervous System

DTIC Science & Technology

1983-11-03

ACh binding to the remaining sites. However, the affinity of oxotremorine to the high affinity agonist binding sites was reduced. The relative...when examined in the remaining sites in the washed membranes, were similar to those in control membranes. The affinity of the agonist oxotremorine ... oxotremorine was substituted for atropine. All determinations were carriid out in quadruplicate, each one varying by < 15%. Centrifugation assays

Pulse Oximeter Plethysmographic Waveform Changes in Awake, Spontaneously Breathing, Hypovolemic Volunteers

DTIC Science & Technology

2011-02-01

Methods of Measurement All subjects were instrumented with 3 Nonin pulse oximeter sensors ( Nonin Medical, Plymouth, MN; OEM III module, 16-bit data...ring finger of the left hand. Unlike standard pulse oximeters that have autocalibration capability, the Nonin pulse oximeter did not alter the raw...stroke volume and are therefore presented as percentage change from baseline levels. The PPG and Spo2 values from the Nonin pulse oxime- ter sensors were

Benzoin Schiff Bases: Design, Synthesis, and Biological Evaluation as Potential Antitumor Agents.

PubMed

Sabbah, Dima A; Al-Tarawneh, Fatima; Talib, Wamidh H; Sweidan, Kamal; Bardaweel, Sanaa K; Al-Shalabi, Eveen; Zhong, Haizhen A; Abu Sheikha, Ghassan; Abu Khalaf, Reema; Mubarak, Mohammad S

2018-04-12

Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds. Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation. A new series of 1,2-diphenylimino ethanol was successfully synthesized and characterized by means of FT-IR, HRMS, NMR, and by elemental analysis. Biological screening revealed that the newly synthesized compounds inhibit PI3Kα activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines. Results additionally showed that these compounds exhibit selective antiproliferative activity, induce apoptosis, and suppress the VEGF production. Compounds 2b, 2d, and 2g displayed promising inhibitory activity in HCT-116 suggesting that hydrophobic and/or hydrogen bond-acceptor mediate(s) ligand-receptor interaction on o- and m-positions. Furthermore, compounds 2g, 2i, 2j, and 2h, bearing hydrophobic moiety on m- and p-position, exerted high antiproliferative activity in T47D and MCF-7 cells, whereas compound 2e showed selectivity against T47D and MCF-7. Molecular docking studies against PI3Kα and caspase-3 demonstrated a strong correlation between the predicted binding affinity (ΔGobsd) and IC50 values of prepared compounds for the caspase-3 model, implying that the cellulous inhibitory activity was caspase-3-dependent. Moreover, Glide docking against PI3Kα identified Ser774, Lys802, E849, V851, and Asp933 as key binding residues. The series exerted a potential PI3Kα inhibitory activity in human carcinoma cell lines expressing PI3Kα. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

In Vivo Reactivation by Oximes of Inhibited Blood, Brain and Peripheral Tissue Cholinesterase Activity Following Exposure to Nerve Agents in Guinea Pigs

DTIC Science & Technology

2010-01-01

L.W.Harris, D.L. Stitcher , Reactivation of VX-inhibited cholinesterase by 2-PAM and HS-6 in rats, Drug Chem. Toxicol. 6 (1983) 235–240. [9] P.M. Lundy, T.-M...rat, monkey and human, Arch. Toxicol. 68 (1994) 648–655. 2 gical In [ [ 14 T.-M. Shih et al. / Chemico-Biolo27] L.W. Harris, W.C. Heyl, D.L. Stitcher

Detoxification of Chemical Warfare Agents by the Plant Cholinergic System

DTIC Science & Technology

2005-10-01

Cholinesterases and Anticholinesterases in Plants , and the First Isolation, Purification and Characterization of Naturally Occurring Activators of... Plants have cholinesterases (pChEs), anti-ChEs, and activators of ChEs. We have isolated pChE from mung bean sprout. We investigated 300 plants ...leaf, “Tritiacche-T123”, activates fetal bovine serum AChE, equine BChE, and pChE. This non-oxime natural plant product may offer a new approach to

Palladium-Catalyzed Nitromethylation of Aryl Halides: An Orthogonal Formylation Equivalent

PubMed Central

Walvoord, Ryan R.; Berritt, Simon; Kozlowski, Marisa C.

2012-01-01

An efficient cross-coupling reaction of aryl halides and nitromethane was developed with the use of parallel microscale experimentation. The arylnitromethane products are precursors for numerous useful synthetic products. An efficient method for their direct conversion to the corresponding oximes and aldehydes in a one-pot operation has been discovered. The process exploits inexpensive nitromethane as a carbonyl equivalent, providing a mild and convenient formylation method that is compatible with many functional groups. PMID:22839593

Antimicrobial effect of Cu(II) complexes containing oxime ligands.

PubMed

Donde, K J; Patil, V R; Malve, S P

2004-01-01

The antibacterial, antifungal and antitubercular activity of Cu(II) complexes was studied. All the complexes have been screened against Staphylococcus aureus, Salmonella typhi, Candida albican, Aspergillus niger, Saccharomyces cerevisiae and H37Rv and found to be more toxic than the parent ligand. The activity increased in the order Cu(5-methyl-2,3-hexanedione dioxime)2 < Cu(5-methyl-3-oximino-hexan-2-o-ne-hydrazone)2 < Cu(5-methyl-3-oximino-hexan-2-one-phenylhydrazone)2.

A Physiologically Based Pharmacokinetic Model for the Oxime TMB-4: Simulation of Rodent and Human Data

DTIC Science & Technology

2013-01-13

concentration gradient–driven diffusion across the membranes, but also on the permeability area (PA) cross product for the tissue, which slows the pene...or slowly (mus- cle, skin, bone) perfused tissues. Diffusion limitation con- stants (permeability area cross products or PAs), metabolism and...al. 1991; Worek et al. 2005). A PBPK model has the advan- tage of interspecies and cross -route extrapolation. This PBPK model was initially developed

The Design, Synthesis and Screening of Potential Pyridinium Oxime Prodrugs.

DTIC Science & Technology

1985-07-31

copper sulfate pentahydrate , and 15 g (87 mol) of the mixture of bromo- picolines 13c and 131. The combined reactions produced 27 g (96%) of a brown...extracted with ethyl ether. The ether extracts were washed with brine, dried with sodium sulfate , filtered and flashed. The residue was then purified by...stirring to the reaction mix. The addition was exothermic as the copper complexes decomposed. The cooled mixture was extracted with several 20 ml

Nonquaternary Cholinesterase Reactivators.

DTIC Science & Technology

1982-08-30

c, a plot (not shown) of pKa versus Hammet substituent constant (a )42 is also linear and conforms p to equation (5) pKa - (7.63 ±0.02) - (.63 ±0.05...dissociates to the active oximate form, we have defined an effective bimolecular reactivation rate constant as in equation (6) keff ’ kb [1 + antilog(pKa...type 1 compounds generally exhibit low activity as reactivators. In terms of keff values [see equation (6)] for reactivation of ethyl methylphosphonyl

Mechanisms of Action of Anticholinesterases and Oximes on Acetylcholine Receptors

DTIC Science & Technology

1988-07-23

Maidstone, England) presoaked in 0.05% polyethylenimine (Sigma, St. Louis, MO) solution (to reduce nonspecific binding). The sample was washed on the...fiber filters presoaked in 0.05% polyethylenimine , using a Cell Harvester (Brandel, Gaithersburg, MD). Filters were washed twice with 5 ml of ice-cold...York). Cells were incubated at 370 in an atmosphere consisting of 10% CO2 and 90% humidified air. The medium was changed on day 3 and day 5 and

Comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX in the rabbit

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

Koplovitz, I.; Stewart, J.R.

1994-12-31

This study compared the efficacy of H16 and 2-PAM against nerve agent (soman tabun sarin and VX) -induced lethality in the atropinesterase-free rabbits pretreated with vehicle (controls) or pyridostigmine. Treatment was administered at signs or 2 min after agent challenge and consisted ofoxime (l00umol/lkg) + atropine 13 mg(kg) (alone or together with diazepam). Twenty-four-h LD50 values were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival was noted in animals given 10 LD50s of sarin or VX. In pyridostigmine and control rabbits intoxicated with soman and treated with oxime + atropine (alone or together with diazepam), HI6 was 35 timesmore » more effective than 2-PAM. In contrast 1116 was less effective than 2-PAM against tabun poisoning. In pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more than 3-fold when compare to tabun-challenged animals treated with atropine + H16 alone. Both oximes were highly effective against satin and VX. These findings suggest that Hifi could replace 2-PAM as therapy for nerve agent poisoning because it is superior to 2-PAM against soman, and when used in pyridostigmine-pretreated animals it affords excellent protection against all four nerve agents when used in combination with atropine (alone or together with diazepam) therapy.« less

Identification and deconvolution of carbohydrates with gas chromatography-vacuum ultraviolet spectroscopy.

PubMed

Schenk, Jamie; Nagy, Gabe; Pohl, Nicola L B; Leghissa, Allegra; Smuts, Jonathan; Schug, Kevin A

2017-09-01

Methodology for qualitative and quantitative determination of carbohydrates with gas chromatography coupled to vacuum ultraviolet detection (GC-VUV) is presented. Saccharides have been intently studied and are commonly analyzed by gas chromatography-mass spectrometry (GC-MS), but not always effectively. This can be attributed to their high degree of structural complexity: α/β anomers from their axial/equatorial hydroxyl group positioning at the C1-OH and flexible ring structures that lead to the open chain, five-membered ring furanose, and six-membered ring pyranose configurations. This complexity can result in convoluted chromatograms, ambiguous fragmentation patterns and, ultimately, analyte misidentification. In this study, mono-, di, and tri-saccharides were derivatized by two different methods-permethylation and oximation/pertrimethylsilylation-and analyzed by GC-VUV. These two derivatization methods were then compared for their efficiency, ease of use, and robustness. Permethylation proved to be a useful technique for the analysis of ketopentoses and pharmaceuticals soluble in dimethyl sulfoxide (DMSO), while the oximation/pertrimethylsilylation method prevailed as the more promising, overall, derivatization method. VUV spectra have been shown to be distinct and allow for efficient differentiation of isomeric species such as ketopentoses and reducing versus non-reducing sugars. In addition to identification, pharmaceutical samples containing several compounds were derivatized and analyzed for their sugar content with the GC-VUV technique to provide data for qualitative analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

A quantum chemical study of molecular properties and QSPR modeling of oximes, amidoximes and hydroxamic acids with nucleophilic activity against toxic organophosphorus agents

NASA Astrophysics Data System (ADS)

Alencar Filho, Edilson B.; Santos, Aline A.; Oliveira, Boaz G.

2017-04-01

The proposal of this work includes the use of quantum chemical methods and cheminformatics strategies in order to understand the structural profile and reactivity of α-nucleophiles compounds such as oximes, amidoximes and hydroxamic acids, related to hydrolysis rate of organophosphates. Theoretical conformational study of 41 compounds were carried out through the PM3 semiempirical Hamiltonian, followed by the geometry optimization at the B3LYP/6-31+G(d,p) level of theory, complemented by Polarized Continuum Model (PCM) to simulate the aqueous environment. In line with the experimental hypothesis about hydrolytic power, the strength of the Intramolecular Hydrogen Bonds (IHBs) at light of the Bader's Quantum Theory of Atoms in Molecules (QTAIM) is related to the preferential conformations of α-nucleophiles. A set of E-Dragon descriptors (1,666) were submitted to a variable selection through Ordered Predictor Selection (OPS) algorithm. Five descriptors, including atomic charges obtained from the Natural Bond Orbitals (NBO) protocol jointly with a fragment index associated to the presence/absence of IHBs, provided a Quantitative Structure-Property Relationship (QSPR) model via Multiple Linear Regression (MLR). This model showed good validation parameters (R2 = 0.80, Qloo2 = 0.67 and Qext2 = 0.81) and allowed the identification of significant physicochemical features on the molecular scaffold in order to design compounds potentially more active against organophosphorus poisoning.

Linearization correction of /sup 99m/Tc-labeled hexamethyl-propylene amine oxime (HM-PAO) image in terms of regional CBF distribution: comparison to C VO2 inhalation steady-state method measured by positron emission tomography

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

Inugami, A.; Kanno, I.; Uemura, K.

1988-12-01

The radioisotope distribution following intravenous injection of 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) in the brain was measured by single photon emission computed tomography (SPECT) and corrected for the nonlinearity caused by differences in net extraction. The linearization correction was based on a three compartment model, and it required a region of reference to normalize the SPECT image in terms of regional cerebral blood flow distribution. Two different regions of reference, the cerebellum and the whole brain, were tested. The uncorrected and corrected HM-PAO images were compared with cerebral blood flow (CBF) image measured by the C VO2 inhalation steady state methodmore » and positron emission tomography (PET). The relationship between uncorrected HM-PAO and PET-CBF showed a correlation coefficient of 0.85 but tended to saturate at high CBF values, whereas it was improved to 0.93 after the linearization correction. The whole-brain normalization worked just as well as normalization using the cerebellum. This study constitutes a validation of the linearization correction and it suggests that after linearization the HM-PAO image may be scaled to absolute CBF by employing a global hemispheric CBF value as measured by the nontomographic TTXe clearance method.« less

Pre- and post-treatment effect of physostigmine on soman-inhibited human erythrocyte and muscle acetylcholinesterase in vitro

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

Herkert, N.M.; Schulz, S.; Wille, T.

2011-05-15

Standard treatment of organophosphorus (OP) poisoning includes administration of an antimuscarinic (e.g., atropine) and of an oxime-based reactivator. However, successful oxime treatment in soman poisoning is limited due to rapid aging of phosphylated acetylcholinesterase (AChE). Hence, the inability of standard treatment procedures to counteract the effects of soman poisoning resulted in the search for alternative strategies. Recently, results of an in vivo guinea pig study indicated a therapeutic effect of physostigmine given after soman. The present study was performed to investigate a possible pre- and post-treatment effect of physostigmine on soman-inhibited human AChE given at different time intervals before ormore » after perfusion with soman by using a well-established dynamically working in vitro model for real-time analysis of erythrocyte and muscle AChE. The major findings were that prophylactic physostigmine prevented complete inhibition of AChE by soman and resulted in partial spontaneous recovery of the enzyme by decarbamylation. Physostigmine given as post-treatment resulted in a time-dependent reduction of the protection from soman inhibition and recovery of AChE. Hence, these date indicate that physostigmine given after soman does not protect AChE from irreversible inhibition by the OP and that the observed therapeutic effect of physostigmine in nerve agent poisoning in vivo is probably due to other factors.« less

The therapeutic use of localized cooling in the treatment of VX poisoning.

PubMed

Sawyer, T W; Mikler, J; Worek, F; Reiter, G; Thiermann, H; Tenn, C; Weatherby, K; Bohnert, S

2011-07-04

The organophosphate (OP) nerve agent VX is a weaponized chemical warfare agent that has also been used by terrorists against civilians. This contact poison produces characteristic signs of OP poisoning, including miosis, salivation, mastication, dysrhythmias and respiratory distress prior to death. Although successful treatment of OP poisoning can be obtained through decontamination and/or oxime reactivation of agent-inhibited cholinesterase, medical countermeasures that increase the therapeutic window for these measures would be of benefit. An anaesthetized swine model was utilized to examine the effects of lethal VX exposure to the skin, followed by cooling the exposure site prior to decontamination or treatment. The cooling was simply accomplished by using crushed ice in grip-seal plastic bags applied to the exposure sites. Cooling of skin exposed to lethal doses of VX significantly increased the window of opportunity for successful decontamination using the Reactive Skin Decontaminant Lotion(®) (RSDL(®)) or treatment with the oxime antidotes HI-6 and 2PAM. Analyses of blood VX levels showed that cooling acted to slow or prevent the entry of VX into the bloodstream from the skin. If the exposure site is known, the simple and non-invasive application of cooling provides a safe means with which to dramatically increase the therapeutic window in which decontamination and/or antidote treatment against VX are life-saving. Copyright © 2011. Published by Elsevier Ireland Ltd.

Non-muscarinic therapeutic targets for acute organophosphorus poisoning.

PubMed

Rosenbaum, Christopher; Bird, Steven B

2010-12-01

Organophosphorus (OP) pesticides are a broad class of acetylcholinesterase inhibitors that are responsible for tremendous morbidity and mortality worldwide, contributing to an estimated 300,000 deaths annually. Current pharmacotherapy for acute OP poisoning includes the use of atropine, an oxime, and benzodiazepines. However, even with such therapy, the mortality from these agents is as high as 40%. It is increasingly recognized that not all OPs are the same. Significant differences exist in their toxicity, lipophilicity, and response to oxime therapy. Other non-muscarinic effects of OP pesticides exist, such as acute and chronic neuromuscular junction failure and central respiratory failure. In part because most of the mortality from these chemicals takes place in the developing world, little National Institutes of Health (NIH) research has been directed towards these agents. However, the similar mechanism of action of OP pesticides and the military nerve agents, along with increasing concerns about chemical terrorism has lead to the formation of the NIH Countermeasures Against Chemical Threats (CounterACT) Program. As part of the CounterACT Program, the NIH has recently designated six OP pesticides as "threat agents". This concept paper describes some of the knowledge gaps related to non-muscarinic effects of OP pesticides and highlights needed areas of further research. Leveraging the current NIH interest in these chemicals to medical necessities in the developing world offers the possibility of delivering new therapeutics where they are needed on a daily basis.

Monitoring chemical reactions by low-field benchtop NMR at 45 MHz: pros and cons.

PubMed

Silva Elipe, Maria Victoria; Milburn, Robert R

2016-06-01

Monitoring chemical reactions is the key to controlling chemical processes where NMR can provide support. High-field NMR gives detailed structural information on chemical compounds and reactions; however, it is expensive and complex to operate. Conversely, low-field NMR instruments are simple and relatively inexpensive alternatives. While low-field NMR does not provide the detailed information as the high-field instruments as a result of their smaller chemical shift dispersion and the complex secondary coupling, it remains of practical value as a process analytical technology (PAT) tool and is complimentary to other established methods, such as ReactIR and Raman spectroscopy. We have tested a picoSpin-45 (currently under ThermoFisher Scientific) benchtop NMR instrument to monitor three types of reactions by 1D (1) H NMR: a Fischer esterification, a Suzuki cross-coupling, and the formation of an oxime. The Fischer esterification is a relatively simple reaction run at high concentration and served as proof of concept. The Suzuki coupling is an example of a more complex, commonly used reaction involving overlapping signals. Finally, the oxime formation involved a reaction in two phases that cannot be monitored by other PAT tools. Here, we discuss the pros and cons of monitoring these reactions at a low-field of 45 MHz by 1D (1) H NMR. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

[A light-cured acrylic adhesive for fixing resin retention devices to the wax pattern].

PubMed

Matsumura, H; Tanaka, T; Atsuta, M

1990-04-01

A light-cured acrylic adhesive for fixing resin retention devices to the wax pattern was prepared. The adhesive consisted of trimethylolpropane triacrylate, 2-ethylhexyl acrylate, benzoin methyl ether, p dimethylaminobenzaldehyde and p-methoxyphenol. The adhesive could be cured within 20 sec not only by an UV photo curing unit but by a visible-light source with a xenon lamp. The adhesive and retention beads burned out after about an hour in the electric furnace at 400 c. The metal specimens with retention devices were cast in Ag-Pd-Cu-Au alloy with the use of two types of retention beads adhesive. The light-cured adhesive was superior to the conventional one in handling and some other properties. This adhesive may be used to fabricate composite veneered prostheses with minimum errors in laboratory procedure.

Diffusion of beta-lactam antibiotics through the porin channels of Escherichia coli K-12.

PubMed Central

Yoshimura, F; Nikaido, H

1985-01-01

Diffusion rates of various beta-lactam antibiotics through the OmpF and OmpC porin channels of Escherichia coli K-12 were measured by the use of reconstituted proteoliposomes. The results can be interpreted on the basis of the gross physicochemical properties of the antibiotics along the following lines. (i) As noted previously (Nikaido et al., J. Bacteriol., 153:232-240, 1983), there was a monotonous dependence of the penetration rate on the hydrophobicity of the molecule among the classical monoanionic beta-lactams, and a 10-fold increase in the octanol-water partition coefficient of the uncharged molecule decreased the penetration rate by a factor of 5 to 6. (ii) Compounds with exceptionally bulky side chains, such as mezlocillin, piperacillin, and cefoperazone, showed much slower penetration rates than expected from their hydrophobicity. (iii) The substituted oxime side chain on the alpha-carbon of the substituent group at position 7 of the cephem nucleus decreased the penetration rate almost by an order of magnitude; this appears to be largely due to the steric effect. (iv) The presence of a methoxy group at position 7 of the cephalosporins also reduced the penetration rate by 20%, probably also due to the steric hindrance. (v) Zwitterionic compounds penetrated very rapidly, and the correlation between the rate and hydrophobicity appeared to be much weaker than with the monoanionic compounds. Imipenem showed the highest permeability among the compounds tested, presumably due, at least in part, to its compact molecular structure. (vi) Compounds with two negative charges penetrated more slowly than did analogs with only one negatively charged group. Among them, only moxalactam, ceftriaxone, and azthreonam showed penetration rates corresponding to, or higher than, 10% of that of imipenem. PMID:2580479

Plasma esterases in the tegu lizard Tupinambis merianae (Reptilia, Teiidae): impact of developmental stage, sex, and organophosphorus in vitro exposure.

PubMed

Basso, Agustín; Attademo, Andrés M; Lajmanovich, Rafael C; Peltzer, Paola M; Junges, Celina; Cabagna, Mariana C; Fiorenza, Gabriela S; Sanchez-Hernandez, Juan Carlos

2012-01-01

In this study, we determined normal serum butyrylcholinesterase (BChE) and carboxylesterase (CbE) activities in Tupinambis merianae in order to obtain reference values for organophosphorus pesticide monitoring. Forty-two T. merianae individuals were grouped by sex and size to identify potential differences in their enzyme levels to allow for proper representation of normal values for females, males, juveniles, and hatchlings. Mean CbE was determined using two model substrates: alpha-naphtylacetate (α-NA) and p-nitrophenyl valerate (4-NPV). BChE and CbE sensitivity to malaoxon (Mx) was also evaluated as well as the possibility of BChE reactivation with pyridine-2-aldoxime methochloride (2-PAM). Mean adult females' BChE was significantly higher than adult males, juveniles, and hatchlings. No significant differences were found between groups regarding CbE. CbE (4-NPV) activity showed slightly negative correlation with lizard snout-vent length, while BChE and CbE (α-NA) showed no correlation with body size. Apparent IC(50) values for BChE and CbE (α-NA) suggested different sensitivities among groups. CbE (4-NPV) could not be inhibited. All Mx-inhibited groups treated with 2-PAM in a final concentration of 2.8 mM showed clear signs of reactivation. In conclusion, the results demonstrate that (1) plasma esterase activity did not vary with age and sex, except for BChE activity, and (2) because biological and environmental variables could be confounding factors in the response of plasma cholinesterases, complementary biomarkers like CbE inhibition and oxime-induced reactivation of esterases are strongly recommended.

Microwave Assisted Synthesis of Py-Im Polyamides

PubMed Central

2012-01-01

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps. PMID:22578091

Nitrolysis of the CN Single Bond and Related Chemistry of Nitro and Nitroso Groups.

DTIC Science & Technology

1988-03-01

oxime of be 4,5-diphenyl-l-triphenylmethoxy-l,23- triazole (11). It was benzoyl cyanide (Scheme 6), for which radical intermediates hydrolysed by...S-Pnitroxide (a radical scavenger) or benzoyl peroxide (a radical *PhC CCN)- NO2 Ag PhCON--CPh suc)I I source). A partial extension of the overall...two anomethylenenitronate anion. (Attempts to prepare the pathways for fragmentation of the ester (3) (C,.H,0 N.O,): one ketenimine (15) by a