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1.
The contribution of the individual enantiomers ([+]-[R]- and [−]-[S]-propranolol) to rac-propranolol intoxication was studied in anaesthetized, spontaneously breathing (SB) rats and artificially ventilated (AV) rats and rabbits. In the SB rat, propranolol (30 mg.kg−1.h−1 i.v.) decreased heart rate and mean arterial blood pressure and caused hypoventilation, serious hypoxaemia, respiratory acidosis, and death by respiratory arrest. Survival time (ST) in the (+)-(R)-propranolol group (ST 91 ± 5 min) was significantly longer than in the rac-propranolol group (ST 68 ± 6 min). In AV rats and rabbits toxic doses of rac-, (−)-(S)- and (+)-(R)-propranolol, 30 mg.kg−1.h−1 and 15 mg.kg−1.h−1 i.v., respectively, induced comparable effects on haemodynamic variables as in the SB rat. Artificial ventilation lengthened ST by a factor of three to four in rats. In the AV rat, ST's were not significantly different between the rac-, (−)-(S)- and (+)-(R)-propranolol groups. In the rabbit, as in the SB rat, ST in the (+)-(R)-propranolol group was significantly longer than ST's in the rac- and (−)-(S)-propranolol groups. The acute respiratory acidosis in SB rats and the prolonged ST in AV rats suggest that respiratory failure is the primary and cardiovascular failure the secondary cause of death in propranolol intoxication. The potentiation of the toxic effect of the enantiomers observed after dosing the racemate instead of the pure enantiomers could not be explained by a stereoselective difference in plasma propanolol concentration. © 1996 Wiley-Liss, Inc.  相似文献   

2.
The crystal structure of the dimeric Ag maleonitriledithiolate complex, Ag2[S2C2(CN)2] [P(C6- H5)3]4 (1), has been performed. Complex 1 crystallizes in the space group P21/c with a = 12.2898(77), b = 23.8325(91), c = 23.1790(118) Å, β = 101.315(43)° and Z = 4. Refinement using 3253 reflections with Fo2>3σ(Fo2) yielded R = 0.0662, Rw= 0.0669. The most interesting aspect of the structure is the strong bridging interaction of the chelating maleonitriledithiolate ligand with the second Ag center, where a Ag-S distance of 2.478 Å is observed. The residual bonding capability of the sulfur atoms in the chelating anion [Ag(S2C2(CN)2)(PPh3)2] for [Ag(PPh3)2]+ is demonstrated.  相似文献   

3.
Summary In a previous communication we reported the racemic synthesis of the cis peptide bond mimic α-benzyl-o-aminomethylphenylacetic acid and its incorporation in the cyclic somatostatin analoguesc[α(R andS)Bn-o-AMPA-Phe7-d-Trp8-Lys9-Thr10]. Since the epimeric peptides exhibit different binding affinities, we completed the structure-activity study with an asymmetric synthesis. A model for the solution conformation ofc[α(R andS)Bn-o-AMPA-Phe7-d-Trp8-Lys9-Thr10] is proposed on the basis of a 2D NMR study in CD3OH and restrained molecular dynamics.  相似文献   

4.
Saplings of four clones of Sitka spruce and cherry were grown for three and two growing seasons, respectively, in open top chambers at two CO2 concentrations (≈ 350 and ≈ 700 μmol mol–1) to determine whether the increase in total biomass brought about by enhanced [CO2] is a result of a transient or persistent effect in nonlimiting conditions. Classical growth analysis was applied to both species and mean current relative growth rate of total dry mass (RT) and leaf dry mass (RL), and period relative growth rate of total dry mass ( ) and leaf dry mass ( ) were calculated. Sitka spruce saplings and cherry seedlings showed a positive growth response to elevated [CO2], and at the end of the experiments both species were ≈ 40% larger in elevated [CO2] than in ambient [CO2]. As a result, the period mean and were significantly higher in elevated [CO2]. The differences in plant dry mass at the end of the experiments were a consequence of the more rapid growth in the early phase of exposure to elevated [CO2]. After this initial phase mean RT and RL were similar or even lower in elevated [CO2] than in ambient [CO2]. NAR of both species was much higher in elevated [CO2], whereas both LAR, SLA, and LMR showed the opposite trend. The higher LAR and SLA of plants in ambient [CO2] contributed to a compensation by which they maintained RT similar to that of elevated [CO2] saplings despite lower NAR and photosynthetic rate. However, when the same size the trees were similar amongst the [CO2] treatments, indicating that one of the main effect of elevated [CO2] on tree growth is to speed-up early development in all aspects.  相似文献   

5.
(Ph4P)4[Tl4Se16] was prepared hydrothermally in a sealed pyrex tube by the reaction of TlCl, K2Se4 and Ph4PCl in a 1:1:1 molar ratio at 110 °C for one day. The red crystals were obtained in 50% yield. Crystals of (Ph4P)4[Tl4Se16]: triclinic P (No. 2), Z=1, a=12.054(9), b=19.450(10), c=11.799(6) Å, α=104.63(4), β=98.86(6), γ=101.99(6)° and V=2555(3) Å3 at 23 °C, 2θmax=40.0°, μ=120.7 cm−1, Dcalc=2.23. The structure was solved by direct methods. Number of data collected: 5206. Number of unique data having Fo2>3σ(Fo2): 1723. Final R=0.075 and Rw=0.089. [Tl4Se16]4− consists of four, almost already linearly arranged, tetrahedral thallium centers which are coordinated by two chelating Se42−, two bridging Se22− and four bridging Se2− ligands. [Tl4Se16]4− sits on an inversion center and possesses a central {Tl2Se2}2+ planar core. The Tl(1)–Tl(1)′ distance in this core is 3.583(6) Å. These two thallium atoms are then each linked to two cyclic Tl(Se4) fragments via bridging Se22− and Se2− ligands forming Tl2Se(Se2) five-membered rings.  相似文献   

6.
The linkage isomers [Re(NCS)6]2? and [Re(NCS)5(SCN)]2? are obtained by the reaction of [ReBr6]2? with NCS? in dimethylformamide. Some differences in the chemical behavior allowed their separation and structural characterization in the form of (NBu4)2[Re(NCS)6] (1) and [Zn(NO3)(Me2phen)2]2[Re(NCS)5(SCN)] (2), respectively (Bu = n-C4H9 and Me2phen = 2,9-dimethyl-1,10-phenanthroline).  相似文献   

7.
A novel nickel(II) hexaaza macrocyclic complex, [Ni(LR,R)](ClO4)2 ( 1 ), containing chiral pendant groups was synthesized by an efficient one‐pot template condensation and characterized (LR,R═1,8‐di((R)‐α‐methylnaphthyl)‐1,3,6,8,10,13‐hexaazacyclotetradecane). The crystal structure of compound 1 was determined by single‐crystal X‐ray analysis. The complex was found to have a square‐planar coordination environment for the nickel(II) ion. Open framework [Ni(LR,R)]3[C6H3(COO)3]2 ( 2 ) was constructed from the self‐assembly of compound 1 with deprotonated 1,3,5‐benzenetricarboxylic acid, BTC3?. Chiral discrimination of rac‐1,1′‐bi‐2‐naphthol and rac‐2,2,2‐trifluoro‐1‐(9‐anthryl)ethanol was performed to determine the chiral recognition ability of the chiral complex ( 1 ) and its self‐assembled framework ( 2 ). Binaphthol showed a good chiral discrimination on the framework ( 2 ). The optimum experimental conditions for the chiral discrimination were examined by changing the weight ratio between the macrocyclic complex 1 or self‐assembled framework 2 and racemates. The detailed synthetic procedures, spectroscopic data including single‐crystal X‐ray analysis, and the results of the chiral recognition for the compounds are described. Chirality, 25:54‐58, 2013 © 2012 Wiley Periodicals, Inc.  相似文献   

8.
Reference ranges of standard experimental parameters are useful for comparisons in toxicology. The aim of this study was to collect data from 13-week repeated toxicity studies in Crl:CD (SD) rats, a strain widely used for toxicity and efficacy research, for establishing domestic reference values. Data on body weight, food consumption; urinalysis, hematological, and blood biochemical parameters; and organ weights were collected from 11 toxicity studies in 220 Crl:CD (SD) rats (110 males and 110 females). The studies had been performed at a single testing facility over the last 5 years and involved animals sourced from a single breeder. The findings were collated as means, standard deviations, percentages, and ranges. Urine volume, uterus weight, eosinophil, and basophil counts, and triglyceride, total bilirubin, and gamma-glutamyl transpeptidase levels showed standard deviations of 30% or more. These historical control data would help to interpret the effects of test substances in routine toxicity and efficacy studies.  相似文献   

9.
The cyclo7,10[Cys7,Cys10,Nle12], cyclo7,10[Cys7,D -Ala9,Cys10,Nle12], and cyclo7,10[Cys7,L -Ala9,Cys10,Nle12] analogues of the α-factor mating pheromone (WHWLQLKPGQPMY) of the yeast Saccharomyces cerevisiae were studied in DMSO/water (80 : 20) and aqueous solution by nmr spectroscopy. In addition, the cyclo7,10[Cys7,D -Val9,Cys10,Nle12] α-factor was examined in DMSO/water. Nuclear Overhauser effect (NOE) and NH dδ/dT data indicate that the cyclo7,10[Cys7,D -Val9,Cys10,Nle12] α-factor adopts a type II β-turn in DMSO/water and that the cyclo7,10[Cys7,D -Ala9,Cys10,Nle12] - and cyclo7,10-[Cys7,L -Ala9,Cys10,Nle12] α-factor analogues adopt type II and type I/III β-turns, respectively, in both DMSO/water and aqueous solutions. In aqueous solution, residues 8 and 9 of the cyclo7,10[Cys7,Cys10,Nle12] α-factor appear to adopt at least two distinct conformations, one of these being identified as a type I/III β-turn. In contrast, the cyclo7,10[Cys7,Cys10,Nle12] α-factor appears to adopt predominately a type II β-turn in DMSO/water. Quantitative NOE measurements of the cyclo7,10[Cys7,Cys10,Nle12]-, cyclo7,10[Cys7,D -Val9,Cys10,Nle12]-, and cyclo7,10[Cys7,L -Ala9,Cys10,Nle12] α-factors in DMSO/water were used to derive three-dimensional structures of the cyclo7,10[Cys7,Pro8,X9Cys10] portion of these analogues. © 1994 John Wiley & Sons, Inc.  相似文献   

10.
《Inorganica chimica acta》1988,148(1):101-104
The compound In[(pz)2BH2]3 (pz = 1-pyrazolyl, C3H3N2) was prepared from In(NO3)3 and K[(pz)2-BH2] in water, and characterised by spectroscopic and X-ray methods. Crystals are orthorhombic,Pna21,a = 20.279(4),b = 8.884(2),c = 13.411(2)Å;R = 0.0285. Individual molecules contain a near-regular six-coordinate indium atom with In–N (av.) 2.241(5)Å. The pyrazolyl borate ligands are puckered, with dihedral angles between the two rings of each ligand in the range 133–144°.  相似文献   

11.
Although rats in various stages of pregnancy are routinely shipped by vendors, the effects of shipping on pregnancy outcomes have not been reported. This study examined the effects of shipping rats 1 day after mating. Two outbred stocks, (Crl:CD(SD), Crl:WI(Han)) and one inbred strain (F344/Crl) of rats (n = 300/strain) were mated in a vendor barrier room at 3‐month intervals five times, and either shipped the next day (total time in transit ~24 hr) or held in the room of origin until parturition. The pregnancy status, length of gestation, number of pups born per female, sex ratio of pups born, and neonatal mortality were compared between transported and nontransported rats. These pregnancy and litter parameters were also compared among strains and examined for seasonality; no seasonal effects were observed. Neonatal mortality was negligible at less than 2% in any of the groups. All sex ratios were normal. Transportation affected pregnancy rates only in the F344/Crl, in which 81.8% of the nontransported versus 70% of the transported rats had pups (p = 0.025). Overall, slightly fewer transported rats were pregnant, but they had larger litters (10.08 compared with 9.68, p = 0.02, pooling across all three strains) so produced the same numbers of pups. A total of 77 ± 8% of transported rats had gestation periods of 22 days or more compared with only 52 ± 10% in the nontransported rats. The reason for larger litters in transported females is unclear. Longer gestation in transported females may be due to facultative embryonic diapause, which might have implications for reproductive toxicology.  相似文献   

12.
Abstract: The psychostimulant drug of abuse, cocaine (benzoylecgonine methyl ester), is rapidly metabolized by cleavage of its two ester groups, to give benzoylecgonine (BE) and ecgonine methyl ester, and by N-demethylation, to give N-norcocaine (NC). The recent use of [N-methyl-11CH3]cocaine to image brain cocaine binding sites with positron emission tomography (PET) raises the question of whether PET images partially reflect the distribution and kinetics of labeled cocaine metabolites. We prepared [O-metty/-11CH3]cocaine by methylation of the sodium salt of BE with [11C]CH3l, and showed that PET baboon brain scans, as well as regional brain kinetics and plasma time-activity curves corrected for the presence of labeled metabolites, are nearly identical to those seen with [N-methyl-11CH3]cocaine. This strongly suggests that 11C metabolites do not significantly affect PET images, because the metabolite pattern is different for the two labeled forms of cocaine. In particular, nearly half the 11C in blood plasma at 30 min was [11C]CO2 when [N-methy/-11CH3]cocaine was administered, whereas [11C]CO2 was not formed from [O-methy/-11CH3]cocaine. Only a trace of [11C]NC was detected in plasma after [O-methyl-11CH3]cocaine administration. Nearly identical brain PET data were also obtained when 4′-[N-methy/-11CH3]fluorococaine and 4′-[18F]fluoro-cocaine (prepared by nucleophilic aromatic substitution from [18F]fluoride-and 4′-nitrococaine) were compared with [N-methy/-11CH3]cocaine. In vitro assays with rat brain membranes showed that cocaine and 4′-fluoroco-caine were equipotent at the dopamine reuptake site, but that 4′-fluorococaine was about 100 times more potent at the 5-hydroxytryptamine reuptake site. The studies with positron-emitting 4′-fluorococaines thus support the lack of significance of labeled metabolites or of binding to 5-hydroxytryptamine reuptake sites to PET images taken with [N-methy/-11CH3]cocaine. [11C]NC prepared by O-methylation of norbenzoylecgonine gave PET images with preferential uptake in striatum, but slower clearance from all brain regions than [O-methy/-11CH3]cocaine. [11C]BE prepared by N-methylation of norbenzoylecgonine did not show brain uptake.  相似文献   

13.
Abstract

Tricyclic (T) analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2) carrying the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system [i.e., 6-(4-BrPh)TACV, 5 and 6-(4-BrPh)TGCV, 6] were transformed into 6-[(4′-R2)-4-biphenylyl] derivatives of TACV (79) and TGCV (1012) by Suzuki cross coupling with 4-substituted phenylboronic acids. Compound 11 (R2 = CH2OH) showed a high (~1000) selectivity index against herpes simplex virus type 1 (HSV-1) together with advantageous fluorescence properties (emission in visible region, little overlap with absorption and moderate intensity).  相似文献   

14.
Pt(II) complexes of the types K[Pt(R2SO)X3], NR4[Pt(R2SO)X3] and Pt(R2SO)2Cl2 (where X = Cl or Br) were characterized by multinuclear magnetic resonance spectroscopy (195Pt, 1H and 13C). In 195Pt NMR, the chloro ionic compounds have shown signals between −2979 and −3106 ppm, while the cis disubstituted complexes were observed at higher fields, between −3450 and −3546 ppm. The signal of the compound trans-Pt(DPrSO)2Cl2 was found at higher field (−3666 ppm) than its cis analogue (−3517 ppm), since π-back-donation is considerably less effective in the trans geometry. In 1H NMR, a single signal was observed for the sulfoxide in [Pt(DMSO)Cl3], but for the other more sterically hindered ligands, two series of resonances were observed for the protons in α and β positions. The coupling constant 3J(195Pt-1H) are between 15 and 33 Hz. The 13C NMR results were interpreted in relation to the concept of inversed polarization of the π sulfoxide bond. The 2J(195Pt-13C) values vary between 35 and 66 Hz, while a few 3J(195Pt-13C) couplings were observed (13-26 Hz). The crystal structures of five monosubstituted ionic compounds N(n-Bu)4[Pt(TMSO)Cl3], N(Me)4[Pt(DPrSO)Cl3], K[Pt(EMSO)Cl3], K[Pt(TMSO)Br3] · H2O and N(Et)4[Pt(DPrSO)Br3] and one disubstituted complex cis-Pt(DBuSO)2Cl2 were determined. The trans influence of the different ligands is discussed.  相似文献   

15.
The relationships between DNA damage and oxidative stress in the digestive gland, gills and haemocytes of the freshwater bivalve Unio tumidus were investigated. Two markers of genotoxicity were measured: DNA breaks by means of the comet assay, and oxidative DNA lesions by means of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) measured using high-performance liquid chromatography (HPLC) coupled to electrochemical detection. Lipid peroxidation was evaluated by measuring malondialdehyde (MDA) tissue levels. Effects were studied after exposure of bivalves for 6 days to benzo[a]pyrene (B[a]P) (50 and 100 μg?l?1) and ferric iron (20 and 40 mg?l?1), applied alone or in combination. Lipid peroxidation in the digestive gland and gills resulted from exposure to Fe3+ or B[a]P whatever the concentrations tested. DNA oxidatively formed lesions were induced in the two tissues at a higher level after B[a]P exposure than after Fe3+ treatment. No significant dose–response relationship was found with the two compounds and no synergistic effect was observed between Fe3+ and B[a]P. The gills appeared less sensitive than the digestive gland to DNA lesions expressed as 8-oxodGuo and comet results. Good correlations were noted between 8-oxodGuo and comet. MDA and DNA damage did not correlate as well, although it was stronger in the digestive gland than in the gills. Production of mucus by the gills likely served to prevent lesions by reducing the bioavailability of the chemicals tested, which could explain that dose–effect relationships and synergistic effects were not observed.  相似文献   

16.
17.
1:1 and 1:2 cobalt complexes of bis(benzimidazol-2-ylmethyl)amine (bbma) bis(benzimidazol-2-ylmethyl)sulfide (bbms), bis(benzimidazol-2-ylethyl)sulfide (bbes) and diethylenetriamine (dien) were prepared and their spectral and redox behavior studied. Two geometrical isomers pink-[Co(bbes)2]2+ and blue-[Co(bbes)2]2+ were obtained when the complexes were prepared by using with bbes and they were separated manually and recrystallized. The octahedral structure of pink-[Co(bbes)2]2+ was resolved by X-ray analysis. The electronic spectra show the presence of two geometrical isomers for Co(bbes)22+ in the solid state; for example, the spectral bands of pink-[Co(bbes)2]2+ differs markedly with those of blue-[Co(bbes)2]2+. This is consistent with the results obtained from magnetic measurements (5.10 BM for pink-Co(bbes)22+ and 4.72 BM for blue-[Co(bbes)2]2+). Further, the behavior of the ligands (bbma, bbms, bbes) at different pH conditions was determined on the basis of 13C NMR studies. The redox potentials [Co(II)/Co(I)] of the complexes follow the trend [Co(bbma)2]2+ < [Co(bbms)2]2+ ≈ [Co(bbes)2]2+ which demonstrates the stabilization of the Co(II) ion is more by both weak σ-donor and weak π-acceptor ligands rather than by σ-donor ligand.  相似文献   

18.
[Pasteurella] pneumotropica biotypes Jawetz and Heyl and [Actinobacillus] muris are the most prevalent Pasteurellaceae species isolated from laboratory mouse. However, mechanisms contributing to their high prevalence such as the ability to form biofilms have not been studied yet. In the present investigation we analyze if these bacterial species can produce biofilms in vitro and investigate whether proteins, extracellular DNA and polysaccharides are involved in the biofilm formation and structure by inhibition and dispersal assays using proteinase K, DNase I and sodium periodate. Finally, the capacity of the biofilms to confer resistance to antibiotics is examined. We demonstrate that both [P.] pneumotropica biotypes but not [A.] muris are able to form robust biofilms in vitro, a phenotype which is widely spread among the field isolates. The biofilm inhibition and dispersal assays by proteinase and DNase lead to a strong inhibition in biofilm formation when added at the initiation of the biofilm formation and dispersed pre-formed [P.] pneumotropica biofilms, revealing thus that proteins and extracellular DNA are essential in biofilm formation and structure. Sodium periodate inhibited the bacterial growth when added at the beginning of the biofilm formation assay, making difficult the assessment of the role of β-1,6-linked polysaccharides in the biofilm formation, and had a biofilm stimulating effect when added on pre-established mature biofilms of [P.] pneumotropica biotype Heyl and a majority of [P.] pneumotropica biotype Jawetz strains, suggesting that the presence of β-1,6-linked polysaccharides on the bacterial surface might attenuate the biofilm production. Conversely, no effect or a decrease in the biofilm quantity was observed by biofilm dispersal using sodium periodate on further biotype Jawetz isolates, suggesting that polysaccharides might be incorporated in the biofilm structure. We additionally show that [P.] pneumotropica cells enclosed in biofilms were less sensitive to treatment with amoxicillin and enrofloxacin than planktonic bacteria. Taken together, these findings provide a first step in understanding of the biofilm mechanisms in [P.] pneumotropica, which might contribute to elucidation of colonization and pathogenesis mechanisms for these obligate inhabitants of the mouse mucosa.  相似文献   

19.
Reaction of [Ru2(O2CMe)4]Cl and K2[Ni(CN)4] forms [Ru2(O2CMe)4]2[Ni(CN)4] with the targeted layered structure possessing Ru-NCNi linkages, albeit strained, with Ru-NC and Ni-CN angles in the range of 147-167°. The magnetic properties of [Ru2(O2CMe)4]2[Ni(CN)4] can be fit to a zero-field splitting model with D/kB = 95 K (66 cm−1).  相似文献   

20.
Large inocula of Stenotrophomonas maltophilia VUN 10,003 were used to investigate bacterial degradation of benzo[a]pyrene and dibenz[a,h]anthracene. Although strain VUN 10,003 was capable of degrading 10–15 mg l−1 of the five-ring compounds in the presence of pyrene after 63 days, further addition of pyrene after degradation of the five-ring polycyclic aromatic hydrocarbons (PAHs) ceased did not stimulate significant decreases in the concentration of benzo[a]pyrene or dibenz[a,h]anthracene. However, pyrene was degraded to undetectable levels 21 days after its addition. The amount of benzo[a]pyrene and dibenz[a,h]anthracene degraded by strain VUN 10,003 was not affected by the initial concentration of the compounds when tested at 25–100 mg l−1, by the accumulation of by-products from pyrene catabolism or a loss of ability by the cells to catabolise benzo[a]pyrene or dibenz[a,h]anthracene. Metabolite or by-product repression was suspected to be responsible for the inhibition: By-products from the degradation of the five-ring compounds inhibited their further degradation. Journal of Industrial Microbiology & Biotechnology (2002) 28, 88–96 DOI: 10.1038/sj/jim/7000216 Received 30 January 2001/ Accepted in revised form 10 October 2001  相似文献   

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