Bromophenols from the red alga Rhodomela confervoides

Six new bromophenols, 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)pyrocatechol (1), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-hydroxymethyldiphenylmethane (2), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxymethyldiphenylmethane (3),(+/-)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde (4), (+/-)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde dimethyl acetal (5), and 3-bromo-4,5-dihydroxybenzoic acid methyl ester (6), together with eight known bromophenols, 3-bromo-4,5-dihydroxybenzaldehyde (7), 2,3-dibromo-4,5-dihydroxybenzyl alcohol (lanosol, 8), 2,3-dibromo-4,5-dihydroxybenzyl methyl ether (9), 2,3-dibromo-4,5-dihydroxybenzyl ethyl ether (10), 2,3-dibromo-4,5-dihydroxybenzylaldehyde (11), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (12), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethylpyrocatechol (13), and 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenyl methane (14), were isolated from the red alga Rhodomela confervoides. Their structures were elucidated by chemical and spectroscopic methods including IR, HRFABMS, and 1D and 2D NMR techniques.

Bromophenol derivatives from the red alga Rhodomela confervoides

Eight new bromophenol derivatives, 2,3-dibromo-4,5-dihydroxybenzyl methyl sulfoxide (1), 4-(2,3-dibromo-4,5-dihydroxyphenyl)-3-butene-2-one (2), 2-(3-bromo-5-hydroxy-4-methoxyphenyl)-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid (3), 2-(3-bromo-5-hydroxy-4-methoxyphenyl)-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid methyl ester (4), 2-phenyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid (5), 4'-methoxy-2",3',3"-tribromo-4",5',5"-trihydroxydiphenylacetic acid (6), and 3-bromo-5-hydroxy-4-methoxyphenylacetic acid (7) and its methyl ester (8), together with a known bromophenol, 3-bromo-5-hydroxy4-methoxybenzoic acid (9), were isolated from the red alga Rhodomela confervoides. Their structures were elucidated by spectroscopic methods including IR, EIMS, FABMS, ESIMS, HRFABMS, HRESIMS, 1D and 2D NMR, and single-crystal X-ray structure analysis. Compounds 1-4, 8, and 9 were found inactive against several human cancer cell lines and microorganisms.

A new brominated phenylpropylaldehyde and its dimethyl acetal from red alga Rhodomela confervoides

A new brominated phenylpropylaldehyde and its dimethyl acetal together with a new natural brominated phenol were isolated from Rhodomela confervoides. Their structrues were elucidated as 2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde, 2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl) propylaldehyde dimethyl acetal and 3-bromo-4,5-dihydroxybenzoic acid methyl ester by spectroscopic techniques including IR, HRFABMS, ID and 2DNMR experiments.

Mechanistic study on spraying of blended biodiesel using phase Doppler anemometry

Droplet size and dynamics of blended palm oil-based fatty acid methyl ester (FAME) and diesel oil spray were mechanistically investigated using a phase Doppler anemometry. A two-fluid atomizer was applied for dispersing viscous blends of blended biodiesel oil with designated flow rates. It was experimentally found that the atomizer could generate a spray with large droplets with Sauter mean diameters of ca. 30 mm at low air injection pressure. Such large droplets traveled with a low velocity along their trajectory after emerging from the nozzle tip. The viscosity of blended biodiesel could significantly affect the atomizing process, resulting in the controlled droplet size distribution. Blended biodiesel with a certain fraction of palm oil-based FAME would be consistently atomized owing to its low viscosity. However, the viscosity could exert only a small effect on the droplet velocity profile with the air injection pressure higher than 0.2 MPa.

Concentration effects of 1,2-dichlorobenzene on soil microbiology

The effect of increasing concentrations (65, 130, 325, 1,300, and 3,250 μg/g soil dry weight) of 1,2-dichlorobenzene (1,2-DCB) on the microbial biomass, metabolic potential, and diversity of culturable bacteria was investigated using soil microcosms. All doses caused a significant (p < 0.05) decrease in viable hyphal fungal length. Bacteria were more tolerant, only direct total counts in soils exposed to 3,250 μg/g were significantly (p < 0.05) lower than untreated controls, and estimates of culturable bacteria showed no response. Pseudomonads counts were stimulated by 1,2-DCB concentrations of up to 325 μg/g; above this level counts were similar to controls. Fatty acid methyl ester analysis of taxonomic bacterial composition reflected the differential response of specific genera to increasing 1,2-DCB concentrations, especially the tolerance of Bacillus to the highest concentrations. The shifts in community composition were reflected in estimates of metabolic potential assessed by carbon assimilation (Biolog) ability. Significantly fewer (p < 0.05) carbon sources were utilized by communities exposed to 1,2-DCB concentrations greater than 130 μg/g (<64 carbon sources utilized) than control soils (83); the ability to assimilate individual carbohydrates sources was especially compromised. The results of this study demonstrate that community diversity and metabolic potential can be used as effective bioindicators of pollution stress and concentration effects.

Response of soil microbial biomass to 1,2-dichlorobenzene addition in the presence of plant residues

The impact of 1,2-dichlorobenzene on soil microbial biomass in the presence and absence of fresh plant residues (roots) was investigated by assaying total vital bacterial counts, vital fungel hyphal length, total culturable bacterial counts, and culturable fluorescent pseudomonads. Diversity of the fluorescent pseudomonads was investigated using fatty acid methyl ester (FAME) characterization in conjunction with metabolic profiling of the sampled culturable community (Biolog). Mineralization of [¹⁴C]1,2- dichlorobenzene was also assayed. Addition of fresh roots stimulated 1,2- dichlorobenzene mineralization by over 100%, with nearly 20% of the label mineralized in root-amended treatments by the termination of the experiment. Presence of roots also buffered any impacts of 1,2-dichlorobenzene on microbial numbers. In the absence of roots, 1,2-dichlorobenzene greatly stimulated total culturable bacteria and culturable pseudomonads in a concentration-dependent manner. 1,2-Dichlorobenzene, up to concentrations of 50 μg/g soil dry weight had little or no deleterious effects on microbial counts. The phenotypic diversity of the fluorescent pseudomonad population was unaffected by the treatments, even though fluorescent pseudomonad numbers were greatly stimulated by both roots and 1,2-dichlorobenzene. The presence of roots had no detectable impact on the bacterial community composition. No phenotypic shifts in the natural population were required to benefit from the presence of roots and 1,2-dichlorobenzene. The metabolic capacity of the culturable bacterial community was altered in the presence of roots but not in the presence of 1,2-dichlorobenzene. It is argued that the increased microbial biomass and shifts in metabolic capacity of the microbial biomass are responsible for enhanced degradation of 1,2-dichlorobenzene in the presence of decaying plant roots.

Response of soil microbial communities to single and multiple doses of an organic pollutant

The effect of 100 μg 1,2-dichlorobenzene (1,2-DCB) g^-1 dry weight (dw) of soil introduced either as a single dose or multiple (10 fortnightly) doses of 10 μg g^-1 dw, on the microbial biomass, diversity of culturable bacterial community and the rate of 1,2-DCB mineralisation, were compared. After 22 weeks exposure both application regimes significantly reduced total bacterial counts and viable fungal hyphal length. The single dose had the greatest overall inhibitory effect, although the extent of inhibition varied throughout the study. Total culturable bacterial counts, determined after 22 weeks exposure showed little response to 1,2-DCB, but pseudomonad counts in single and multiple treatments were reduced to 9.7 and 0.147%, respectively, of the numbers detected in the control soil. The effect of 1,2-DCB application on the taxonomic composition of the culturable bacteria community was determined by fatty acid methyl ester (FAME) analysis. Compared to control soils, the single dose treatment had a lower percentage of Arthrobacter and Micrococcus. Multiple applications had a significant effect upon pseudomonad abundance, which represented only 2% of the identified community, compared to 45.6% in the control. The multi-dosed soils contained a high percentage of bacilli (> 25%). The effects of 1,2-DCB applications on the metabolic potential of the soil microbial community was determined by BIOLOG profiling. The number of carbon compounds utilised by the community in the multi-dosed soils (49 positives) was significantly less (P < 0.05) than detected in the single dose treatment (76) and control (66). The rate of 1,2-DCB mineralisation, determined by ¹⁴CO₂ production from radiolabelled [UL-¹⁴C] 1,2-DCB, declined throughout the study, and after 22 weeks was slightly but significantly (P < 0.05) lower in the multiply- than the singly-dosed soils. The differential response to 1,2-DCB treatments was attributed to its reduced bioavailability in soils after a single exposure, compared to multiple applications.

Extraction and purification of triterpenic acids from eucalypt bark

A indústria da pasta e do papel é um sector importante da economia mundial, particularmente a que assenta em espécies de Eucalyptus. No entanto, essas indústrias geram quantidades significativas de correntes secundárias de subprodutos e resíduos de biomassa que podem ser exploradas em aplicações de valor acrescentado em vez de serem queimadas para produção de energia. Um exemplo nobre pode ser a produção de ácidos triterpénicos com estruturas dos tipos lupano, oleanano e ursano, dada a sua abundância em alguns destes resíduos, em particular na casca, adotando o conceito de biorrefinaria integrada numa fábrica de pasta. Estes compostos são conhecidos pelas suas inúmeras actividades biológicas, por exemplo, antioxidante, anti-inflamatória e antitumoral, e podem encontrar aplicações em produtos de elevado valor, tais como cosméticos, nutracêuticos ou farmacêuticos. Neste sentido, o estudo das potencialidades das cascas das espécies de eucalipto mais exploradas enquanto fontes de compostos triterpénicos é um tópico relevante. Por conseguinte, foram analisados e comparados em pormenor os teores e composições em ácidos triterpénicos (TTAs) das cascas externas de várias espécies de eucalipto (E. globulus, E. grandis, E. urograndis, E. maidenii e E. nitens). Os teores dos principais TTAs identificados nestas espécies variaram entre 4.5 g/kg no E. urograndis e 21.6 g/kg no E. nitens. Observou-se que as cascas externas de Eucalyptus de zonas temperadas e Mediterrânicas, nomeadamente E. nitens e E. globulus, são mais ricas em TTAs que as espécies de regiões tropicais e subtropicais. Além disso, a casca externa do E. globulus é claramente a mais rica em ácidos com estruturas do tipo ursano enquanto a do E. nitens é a mais rica em ácidos do tipo oleanano e lupano. Estes resultados levaram-nos a estudar a extração dos TTAs da casca de Eucalyptus, bem como a sua posterior concentração e purificação, a qual foi efetuada por extração sólido-líquido convencional combinada com a precipitação de solutos, e por extração com fluidos supercríticos (SFE). No que diz respeito à primeira abordagem referida, foi desenvolvido neste trabalho um método patenteado que permite obter extratos enriquecidos em TTAs das cascas de eucalipto baseado em tecnologias disponíveis no imediato. Em relação à segunda abordagem, e de forma a apostar em processos de baixo impacto ambiental exigidos pelas biorrefinarias do futuro, a SFE surge como uma opção natural. Assim, foi efetuada a SFE da casca caduca do E. globulus com dióxido de carbono puro e modificado para recuperar a fração de TTAs, e os resultados foram comparados com os obtidos por extração em Soxhlet com diclorometano. Foram realizados estudos preliminares sobre a influência da pressão (100-200 bar), a adição de co-solvente (0, 5 e 8% m/m de etanol), e operação em múltiplos passos a fim de avaliar a aplicabilidade da alternativa supercrítica para a sua produção eficiente e selectiva. Os resultados destacaram a influência da pressão e o importante papel resumo (cont.) desempenhado pelo co-solvente neste processo, cujo efeito foi mais relevante do que o aumento da pressão em várias dezenas de bar. Este trabalho foi depois otimizado, usando o planeamento factorial de experiências e a metodologia de superfícies de resposta, para analisar a influência da temperatura (40-60 ºC), pressão (100-200 bar), e teor de etanol (0.0-5.0% m/m) na recuperação dos TTAs e respectiva concentração nos extractos. Nestes intervalos, as melhores condições de operação encontradas foram 200 bar, 40 °C e 5% de etanol, para as quais os modelos de regressão estatisticamente validados previram um rendimento de extração de 1.2% com 50% de concentração em TTAs, correspondendo ao rendimento em TTAs de 5.1 g/kg de casca e uma recuperação de 79.2% comparativamente ao valor do Soxhlet. Os TTAs livres e acetilados apresentaram tendências de extracção bastante distintas devido às suas diferentes afinidades para o CO2 causadas pelas diferentes polaridades: os derivados acetilados aproximam-se de um patamar máximo a cerca de 200 bar e 5% de etanol, enquanto a extração dos TTAs livres apresenta uma tendência sempre crescente no intervalo de condições estudado. Foram também medidas curvas cumulativas de SFE da casca do E. globulus de forma a analisar o comportamento cinético do processo em termos de rendimento total, rendimento em TTAs, rendimento em TTAs livres, rendimento em TTAs acetilados, e concentração dos TTAs nos extractos. Foi analisada a influência da pressão, temperatura, teor de co-solvente e caudal do dióxido de carbono sobre as respostas anteriores. Os dados experimentais foram modelados com os modelos Logístico, de Dessorção, de Placa Plana Simples, e de Difusão. Na globalidade, os resultados confirmaram que a pressão e o teor de etanol têm um efeito significativo sobre as curvas de extração, os rendimentos finais e as concentrações dos extratos, e mostraram a presença de limitações externas à transferência de massa em alguns ensaios. Mais uma vez, as famílias individuais de TTAs livres e acetilados apresentaram diferentes tendências de extracção. A modelação permitiu-nos confirmar não só o importante papel desempenhado pela difusão intraparticular na SFE, mas também a contribuição da resistência no filme em alguns ensaios. Após a análise de todos os resultados, foi efetuado um ensaio em duas etapas em série, possibilitando o enriquecimento do teor em TTAs no extracto devido às diferentes condições adotadas em cada etapa. Por último, um éster metílico de um ácido triterpénico do tipo oleanano - morolato de metilo - foi identificado pela primeira vez enquanto componente da casca de Eucalyptus na casca externa do Eucalyptus grandis x globulus, onde ocorre em teores elevados. A sua extração com CO2 supercrítico foi também realizada, visando a conceção de uma alternativa de extração ambientalmente benigna para este composto. A 200 bar e 60 ºC, a remoção do morolato de metilo atingiu um patamar às 6 h para 5.1 kg h-1 de CO2 / kg de casca. Em geral, e de forma semelhante à SFE da casca do E. globulus, os TTAs acetilados foram mais significativamente extraídos quando comparados com os seus ácidos livres, o que está diretamente relacionado com a natureza menos polar destas moléculas. O trabalho apresentado nesta tese é uma contribuição para a valorização de uma corrente de biomassa com baixo valor na indústria de pasta em duas vertentes complementares. Por um lado, aumentou o conhecimento da composição lipofílica das cascas de Eucalyptus spp. com interesse comercial para a produção de pasta, destacando o seu potencial enquanto fontes de ácidos triterpénicos. Por outro lado, foram desenvolvidos dois processos alternativos e facilmente integráveis numa fábrica de pasta para a sua exploração a partir da casca: um baseado em tecnologias convencionais bem estabelecidas a nível industrial, prevendo a sua aplicação a curto prazo, e um outro baseado na SFE, seguindo as tendências das futuras biorrefinarias.

A mass spectrometric study of some pesticides /|nK. S. Subramanian. -- 260 St. Catharines, Ont. : [s. n.],

The fragmentation processes in the mass spectra of a series of organophosphorus, organochlorine, thio and dithiocarbamate as well as a number of miscellaneous pesticides have been studied i n detail by using the Bendix timeof- flight, MS-12 single-focussing and MS-30 double-focussing mass spectrometers. Interpretation of all the spectra have been presented; their mode s of dissociation elucidated, aided by metastable transitions wherever possible and the structures of the various f ragmentation species postulated wherever f easible. The fragmentation mechanisms are based on the concepts of inductive, resonance and steric ef~ects. Multiple bond cleavages accompanied by simultaneous bond formation and rearrangement reactions involving cycli c t r ansition states have clarified t he formation of various ions . Due emphasis has been placed on the effect of the functional groups or substituents in altering the mass spectral behaviour of the pesticides as they form the basis for the identifi cation of the otherwise identical pesticides. The organophosphorus pesticides which have been studied include i) the phosphates (eg: DDVP and Phosdrin ); ii) phosphorothionates (eg: Parathion, 0-2, 4 dichloro phenyl 0, O-diethyl thionophosphate); iii) phosphorothioites (eg: Tributyl phosphorotrithioite); i V) phosphorothioates (eg: Ethion) and v) phosphorodithioates (eg: Carbophenolthion). Cleavages and rearrangements of the ester moiety dominate the spectrum of phosdrin while that of DDVP is + dominated by t he fragmentation modes of the (OH30)2P=0 + moiety. Fragmentation §f the (CH30)2P=S characterises the spectrum of (OH30)2"P -Cl while cleavages of the + (C2H50 )2P=S species mark the spectra of parathion and 0-2, 4- di chlorophenyl O, O-diethyl thiophosphate. The 0(, cl eavages of the thioether f unction rather than + cleavages of the (C2H50)2P=S signify the spectrum of carbophenolthion. Tributyl phosphorotrithioite behaves more like an aliphatic hydrocarbon than like the corresponding phosphites. The isopropyl and butyl esters of 2, 4 dichlorophenoxy acetic acid show cleavage and rearrangement ions typical of an ester. In spite of its structural similari ty to pp' - DDT and pp' - DDD, Kalthane has a completely different mass spectral behaviour due to the influence of its hydroxyl function. The thiocarbamate pesticides studied include Eptam and Perbulate. Both are structurally similar but having different alkyl substituents on nitrogen and sulphur. This structurQlsimilarity leads to similar types of (N-C), (O-S) and (S-alkyl cleavages). However, perbulate differs from Eptam in showing a rearrangement ion at mle 161 and in forming an isocyanate ion as the base peak. In Eptam the base peak i s the alkyl ion. The dithiocarbamate, Vegadex, resembles the thiocarbamates in undergoing simple cleavages but it differs from them in having a weak parent ion; in the formation of its base peak and in undergoing a series of rearrangement reactions. The miscellaneous pesticides studied include 1-Naphthalene acetic aCid- methyl ester, Fiperonyl butoxide and Allethrin. The ester i s stable to electron impact and shows only fewer ions. Piper onyl butoxide, a polyether, shows characteristics of an et her, alcohol and aldehyde . Allethrin is regarded as an ester of the type R-C-O-R1 with n R being a substituted cyclopr opane moiety and o Rt, a substituted cyclopentenone mOiety. Accordingly it shows cleavage ions typical of an aliphatic ester and undergoes bond ruptures of the cyclic moieties to give unusual ions. Its base peak is an odd electron ion, quite contrary to expectations.

Antidiabetic activity of Vaccinium vitis-idaea, a medicinal plant from the traditional pharmacopeia of the James Bay Cree

L’incidence du diabète chez les premières nations du Canada est plus de trois fois celle du reste du pays, dû, en partie, aux traitements culturellement inappropriés. Notre projet vise à traiter le diabète chez ces populations à partir de leur pharmacopée de médicine traditionnelle afin d’améliorer l’acceptation des traitements. En utilisant une approche ethnobotanique, notre équipe a identifié 17 plantes médicinales utilisées pour traiter des symptômes du diabète par les Cris d'Eeyou Istchee (Baie James, Québec). Parmi eux, l'extrait éthanolique de baies de Vaccinium vitis-idaea a montré un effet stimulateur sur le transport du glucose dans les cellules musculaires squelettiques et les adipocytes en culture. Le but de cette thèse était d’élucider les mécanismes par lesquels cet extrait exerce ses effets anti-hyperglycémiants, d’identifier ses principes actifs et de confirmer in vivo, son efficacité. Les résultats démontrent que V.vitis a augmenté le transport du glucose dans les cellules musculaires en cultures, C2C12 et L6 et a stimulé la translocation des transporteurs GLUT4 dans les cellules L6. L'extrait a également inhibé la respiration dans les mitochondries isolées du foie du rat. Cet effet est semblable à celui de la metformine et en lien avec la production du stress métabolique et l'activation de l'AMPK. De plus, la voie de signalisation de l’insuline ne semble pas être impliquée dans le mécanisme d’action de V. vitis. Le fractionnement guidé par la stimulation du transport du glucose a mené à l'isolation des principes actifs; la quercétine, la quercétine-3-O-galactoside, et la quercétine-3-O-glucoside. Comparable à l'extrait brut, ses composés ont stimulé la voie AMPK. Cependant, la quércetine était la seule à inhiber la respiration mitochondriale. Pour valider l'effet de V.vitis in vivo, l'extrait (1% dans l'eau de boisson) a été administré aux souris KKAy pendant 10 jours. La glycémie et le poids corporel ont été significativement réduits par V.vitis. Ces effets ont été associés à une diminution de la prise alimentaire, ce qui suggère que V.vitis diminue l'appétit. L'étude pair-fed a confirmé que les effets de V.vitis sont, majoritairement, dû à la réduction de l’appétit. De plus, V.vitis a augmenté la teneur en GLUT4 dans le muscle squelettique, a stimulé la iv phosphorylation de l'ACC et a augmenté les niveaux de PPAR-α dans le foie des souris KKAy. Ces effets se voient être additifs à l’effet anorexigène de V. vitis. Au cours du fractionnement bioguidé de l’extrait, l’ester méthylique de l'acide caféique (CAME), un produit formé lors de la procédure du fractionnement, a démontré un effet stimulateur puissant sur le transport du glucose dans les celules C2C12 et donc un potentiel anti-diabétique. Pour identifier d'autres acides caféique active (AC) et pour élucider leurs relations structure-activité et structure-toxicité, vingt dérivés AC ont été testés. Outre CAME, quatre composés ont stimulé le transport du glucose et ont activé l'AMPK suite au stress métabolique résultant d'un découplage de la phosphorylation oxydative mitochondriale. L’activité nécessite une fonction d’AC intacte dépourvu de groupements fortement ionisés et ceci était bien corrélée avec la lipophilicite et la toxicité. Les résultats de cette thèse soutiennent le potentiel thérapeutique de V. vitis, ses composés actifs ainsi que de la famille de l’AC et pour la prévention et le traitement du diabète.

Synthesis and characterization of a new mebendazole salt: Mebendazole hydrochloride

Mebendazole hydrochloride [(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester hydrochloride, MBZ.HCl], a new stable salt of mebendazole (MBZ), has been synthesized and characterized. It can easily be obtained from recrystallization of forms A, B, or C of MBZ in diverse solvents with the addition of hydrochloric acid solution. Crystallographic data reveals that the particular conformation adopted by the carbamic group contributes to the stability of the network. The crystal packing is stabilized by the presence of three N-H...Cl intermolecular interactions that form chains along the b axis. The XRD analyses of the three crystalline habits found in the crystallization process (square-based pyramids, pseudohexagonal plates, and prismatic) show equivalent diffraction patterns. The vibrational behavior is consistent with crystal structure. The most important functional groups show shifts to lower or higher frequencies in relation to the MBZ polymorphs. The thermal study on MBZ center dot HCI indicates that the compound is stable up to 160 degrees C approximately. Decomposition occurs in four steps. In the first step the HCl group is eliminated, and after that the remaining MBZ polymorph A decomposes in three steps, as happens with polymorphs B and C. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:542-552, 2008.

Preferential location of lidocaine and etidocaine in lecithin bilayers as determined by EPR, fluorescence and H-2 NMR

We have examined the effect of the uncharged species of lidocaine (LDC) and etidocaine (EDC) on the acyl chain moiety of egg phosphatidylcholine liposomes. Changes in membrane organization caused by both anesthetics were detected through the use of EPR spin labels (5, 7 and 12 doxyl stearic acid methyl ester) or fluorescence probes (4, 6, 10, 16 pyrene-fatty acids). The disturbance caused by the LA was greater when the probes were inserted in more external positions of the acyl chain and decreased towards the hydrophobic core of the membrane. The results indicate a preferential insertion of LDC at the polar interface of the bilayer and in the first half of the acyl chain, for EDC. Additionally, 2 H NMR spectra of multilamellar liposomes composed by acyl chain-perdeutero DMPC and EPC (1:4 mol%) allowed the determination of the segmental order (S-mol) and dynamics (T-1) of the acyl chain region. In accordance to the fluorescence and EPR results, changes in molecular orientation and dynamics are more prominent if the LA preferential location is more superficial, as for LDC while EDC seems to organize the acyl chain region between carbons 2-8, which is indicative of its positioning. We propose that the preferential location of LDC and EDC inside the bilayers creates a ""transient site"", which is related to the anesthetic potency since it could modulate the access of these molecules to their binding site(s) in the voltage-gated sodium channel. (C) 2007 Elsevier B.V. All rights reserved.

Preferential location of lidocaine and etidocaine in lecithin bilayers as determined by EPR, fluorescence and H-2 NMR

We have examined the effect of the uncharged species of lidocaine (LDC) and etidocaine (EDC) on the acyl chain moiety of egg phosphatidylcholine liposomes. Changes in membrane organization caused by both anesthetics were detected through the use of EPR spin labels (5, 7 and 12 doxyl stearic acid methyl ester) or fluorescence probes (4, 6, 10, 16 pyrene-fatty acids). The disturbance caused by the LA was greater when the probes were inserted in more external positions of the acyl chain and decreased towards the hydrophobic core of the membrane. The results indicate a preferential insertion of LDC at the polar interface of the bilayer and in the first half of the acyl chain, for EDC. Additionally, 2 H NMR spectra of multilamellar liposomes composed by acyl chain-perdeutero DMPC and EPC (1:4 mol%) allowed the determination of the segmental order (S-mol) and dynamics (T-1) of the acyl chain region. In accordance to the fluorescence and EPR results, changes in molecular orientation and dynamics are more prominent if the LA preferential location is more superficial, as for LDC while EDC seems to organize the acyl chain region between carbons 2-8, which is indicative of its positioning. We propose that the preferential location of LDC and EDC inside the bilayers creates a "transient site", which is related to the anesthetic potency since it could modulate the access of these molecules to their binding site(s) in the voltage-gated sodium channel. (C) 2007 Elsevier B.V. All rights reserved.

Similar anxiolytic-like effects following intra-amygdala infusions of benzodiazepine receptor agonist and antagonist: Evidence for the release of an endogenous benzodiazepine inverse agonist in mice exposed to elevated plus-maze test

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Clerodane diterpenes from Aristolochia species

The investigation of Aristolochia brasiliensis and A. esperanzae afforded 12 clerodane derivatives, including the following six novel ones: rel (5S, 8R, 9S, 10R)-2-oxo-ent-3-cleroden-15-oic acid, rel (5S, 8R, 9S, 10R)-2-oxo-ent-clerod-3,13-dien-15-oic acid methyl ester, (5R, 8R, 9S, 10R)-ent-3-cleroden-15-oic acid, rel (5S, 8R, 9S, 10R)-ent-clerod-3,13-dien-15-oic acid, (2S, 5R, 8R, 9S, 10R)-2-hydroperoxy-ent-3-cleroden-15-oic acid methyl ester and (2S, 5R, 8R, 9S, 10R)-2-hydroperoxy-ent-clerod-3,13-dien-15-oic acid methyl ester. The structures were assigned on the basis of spectral data and derivatization by chemical reactions. The occurrence of this type of diterpene has not previously been reported in Aristolochiaceae. © 1987.