Abstract  IMAC can be used to selectively enrich phosphopeptides from complex peptide mixtures, but co-retention of acidic peptides together with the failure to retain some phosphopeptides restricts the general utility of the method. In this study Fe(III)-IMAC was qualitatively and quantitatively assessed using a panel of phosphopeptides, both synthetic and derived from proteolysis of known phosphoproteins, to identify the causes of success and failure in the application of this technique. Here we demonstrate that, as expected, peptides with a more acidic amino acid content are generally more efficiently purified and detected by MALDI-MS after Fe(III)-IMAC than those with a more basic content. Modulating the loading buffer used for Fe(III)-IMAC significantly affects phosphopeptide binding and suggests that conformational factors that lead to steric hindrance and reduced accessibility to the phosphate are important. The use of 1,1,1,3,3,3-hexa-fluoroisopropanol is shown here to significantly improve Fe(III)-IMAC enrichment and subsequent detection of phosphopeptides by MALDI-MS.

Abstract  BACKGROUND: Aromatic anesthetics exhibit a wide range of N-methyl-D-aspartate We sought to (NMDA) receptor inhibitory potencies and immobilizing activities. characterize the molecular basis of NMDA receptor inhibition using comparative molecular field analysis (CoMFA), and compare the results to those from an equivalent model for immobilizing activity. METHODS: Published potency data for 14 compounds were Supplemented with new values for 2 additional agents. The anesthetics were divided into a training set (n = 4) used to formulate the activity models and a test set (n = 4) used to independently, assess the models' predictive capability. The anesthetic structures were geometry optimized using ab initio quantum mechanics and aligned by field-fit minimization to provide the best correlation between the steric and electrostatic fields Of the Molecules and one or more lead structures. Orientations that yielded CoMFA models with the greatest predictive capability (assessed by leave-one-out cross-validation) were retained. RESULTS: The final CoMFA model for the inhibition of NR1/NR2B NMDA receptors explained 99.3%, of the variance in the observed activities of the 12 training set agents = (F-2,F-9 = 661.5, P < 0.0001). The model effectively predicted inhibitory potency for the training set (cross-validaed r(2) (CV) = 0.944) and 4 excluded test set compounds (predictive r(2) (Pred) = 0.966). The equivalent model for immobility in response to noxious Stimuli explained 98.0% of the variance in the observed activities for the training set (F-2,F-9 = 219.2, P < 0.0001) and exhibited adequate predictive capability for both the trainnig set (r(2) (CV) = 0.872) and test set (r(2) (Pred) = 0.926) agents. Comparison of pharmacophoric maps showed that several key steric and electrostatic regions were common to both activity models, but differences were observed in the relative importance of these key regions with respect to the two aspects of anesthetic activity. CONCLUSIONS: The similarities in the pharmacophoric maps are consistent with NMDA receptors contributing part of the immobilizing activity of volatile aromatic anesthetics.

Abstract  By using pharmacological approaches and laser scanning confocal microscopy (LSCM) based on 4, 5-diaminofluorescein diacetate (DAF-2 DA), the roles of MAPKK/CDPK and their effects on nitric oxide (NO) levels of guard cells during darkness-induced stomatal closure in broad bean were investigated. The results indicated that both 2'-amino-3'-methoxyflavone (PD98059) (an inhibitor of mitogen-activated protein kinase kinase, MAPKK) and trifluoperazine (TFP) (a specific inhibitor of calcium-dependent protein kinase, CDPK) reduced the levels of NO in guard cells and significantly reversed darkness-induced stomatal closure, implying that MAPKK/CDPK mediate darkness-induced stomatal closure by enhancing NO levels in guard cells. In addition, as with NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), but not with nitric oxide synthase inhibitor N-G-nitro-L-Arg-methyl ester (L-NAME), PD98059 and TFP not only reduced 4,5-diaminofluorescein diacetate (DAF-2 DA) fluorescence in guard cells by sodium nitroprusside (SNP) in light, but also abolished NO that had been generated during a dark period, and reversed stomatal closure by SNP and by darkness, suggesting MAPKK and CDPK are probably related to restraining the NO scavenging to elevate NO levels in guard cells, during darkness-induced stomatal closure. The results also showed that both PD98059 and TFP reduced stomatal closure by SNP, implying that the possibility of MAPKK and CDPK acting as the target downstream of NO should not be ruled out. There may be a causal and interdependent relationship between MAPKK/CDPK and NO in darkness-induced stomatal closure, and in the process this cross-talk may lead to the formation of a self-amplification loop about them.

Abstract  The FDC-specific molecular signals required in the formation of FDC networks, B cell follicles, and germinal centers (GCs) have remained poorly understood. We used FDC-specific gene targeting to investigate the function of p55TNFR and IKK2 in lymphoid organ structure and function. Here we show that FDC-specific expression of p55TNFR is necessary and sufficient to promote FDC network and B cell follicle formation, restore the expression of CXCL13 and VCAM-1/ICAM-1 in FDCs, and lead to productive GCs. Notably, FDC-specific disruption of IKK2 does not affect formation of FDC networks. Yet, after antigen engagement or immune complex (IC) deposition, FDCs lacking IKK2 fail to upregulate VCAM-1 and ICAM-1, and GCs remain sterile. These findings demonstrate that IKK2-independent function of p55TNFR on FDCs is sufficient to support the development of FDC networks and GCs, while FDC-specific IKK2 is indispensable for the generation of efficient humoral immune responses.

Abstract  Two cases of atrial fibrillation and one case of sudden death occurred in workers exposed to trifluorotrichloroethane (CFC 113) as a solvent/degreasing agent. This agent and related halogenated hydrocarbons are widely used in industry as solvents and degreasing agents, and have been previously linked to ventricular arrhythmias and cardiac sudden death when inhaled in excessive concentrations. We suggest that occupational overexposure to halogenated hydrocarbons should be considered a potential precipitant for atrial as well as ventricular arrhythmias.

Abstract  This study reports two occupational deaths resulting from exposure to fluorocarbon-113 (1,1,2-trichloro-1,2,2-trifluoroethane; FC-113) in enclosed and confined spaces. One incident involved a worker who was exposed to FC-113 after entering a small degreasing tank to clean it. The second case involved a significant spill of FC-113 onboard a marine vessel. The incidents are compared to other fatal exposures.

Abstract  This paper demonstrates how a quantum cascade laser (QCL) in its intrapulse mode can provide a simple method for probing the products of a photolysis event. The system studied is the 266 nm photodissociation of CF3I with the CF3 fragments subsequently detected using radiation at similar to 1253 cm(-1) generated by a pulsed QCL. The tuning range provided by the frequency down-chirp of the QCL operated in its intrapulse mode allows a similar to 1 cm(-1) segment of the CF3 nu(3) band to be measured following each photolysis laser pulse. Identification of features within this spectral region allows the CF3 (nu = 0) number density to be calculated as a function of pump-probe delay, and consequently the processes which populate and deplete this quantum state may be examined. Rate constants for the population cascade from higher vibrational levels into the nu = 0 state, k(1), and for the recombination of the CF3 radicals to form C2F6, k(2), are measured. The returned values of k(1) = (2.3 +/- 0.34) x 10(-12) cm(3) molecule(-1) and k(2) = (3.9 +/- 0.34) x 10(-12) cm(3) molecule(-1) s(-1) are found to be in good agreement with reported literature values.

Abstract  A bimolecular rate constant, k(OH+Benzyl alcohol), of (28 +/- 7) x 10 (12) cm(3) molecule (1) s(-1) was measured using the relative rate technique for the reaction of the hydroxyl radical (OH) with benzyl alcohol, at (297 +/- 3)K and 1 atm total pressure. Additionally, an upper limit of the bimolecular rate constant, k(O3+Benzyl alcohol), of approximately 6 x 10(-19)cm(3) molecule(-1) s (1) was determined by monitoring the decrease in benzyl alcohol concentration overtime in an excess of ozone (O-3). To more clearly define part of benzyl alcohol's indoor environment degradation mechanism, the products of the benzyl alcohol + OH were also investigated. The derivatizing agents O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) and N,O-bis(trimethylsilyl) tr fluoroacetamide (BSTFA) were used to positively identify benzaldehyde, glyoxal and 4-oxopentanal as benzyl alcohol/OH reaction products. The elucidation of other reaction products was facilitated by mass spectrometry of the derivatized reaction products coupled with plausible benzyl alcohol/OH reaction mechanisms based on previously published volatile organic compound/OH gas-phase reaction mechanisms. Published by Elsevier Ltd.

Abstract  Background: Nitric oxide is known to be essential for early anesthetic preconditioning (APC) and ischemic preconditioning (IPC) of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, the authors tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. Methods: Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning within 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (W), and with or without pretreatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or N-G-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or N(G)w-nitro-L-arginine methyl ester. interactions between Hsp90 and eNOS, and eNOS activation, were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. Results: APC and IPC decreased infarct size (by 50% and 59%, respectively), and this action was abolished by Hsp90 inhibitors. N-G-nitro-L-arginine methyl ester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes, and eNOS was below the level of detection. Conclusion: The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signaling during APC.

Abstract  Peroxynitrite is a powerful oxidant capable of nitrating phenolic moieties, such as tyrosine or tyrosine residues in proteins and increases after traumatic brain injury (TBI). First, we tested the hypothesis that TBI increases nitrotyrosine (NT) immunoreactivity in the brain by measuring the number of NT-immunoreactive neurons in the cerebral cortex and hippocampus of rats subjected to parasagittal fluid-percussion TBI. Second, we tested the hypothesis that treatment with L-arginine, a substrate for nitric oxide synthase, further increases NT immunoreactivity over TBI alone. Rats were anesthetized with isoflurane and subjected to TBI, sham TBI, or TBI followed by treatment with L-arginine (100 mg/kg). Twelve, 24, or 72 h after TBI, brains were harvested. Coronal sections (10 μm) were incubated overnight with rabbit polyclonal anti-NT antibody, rinsed, and incubated with a biotinylated secondary antibody. The antigen–antibody complex was visualized using a peroxidase-conjugated system with diaminobenzidine as the chromagen. The number of NT-positive cortical and hippocampal neurons increased significantly in both ipsilateral and contralateral hemispheres up to 72 h after TBI compared with the sham-injured group. Remarkably, treatment with L-arginine reduced the number of NT-positive neurons after TBI in both cortex and hippocampus. Our results indicate that L-arginine actually prevents TBI-induced increases in NT immunoreactivity.Journal of Cerebral Blood Flow & Metabolism (2008) 28, 1733–1741; doi:10.1038/jcbfm.2008.66; published online 9 July 2008 [ABSTRACT FROM AUTHOR] Copyright of Journal of Cerebral Blood Flow & Metabolism is the property of Nature Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Abstract  Ferrous chloride was employed as additive in preparing flat sheet poly(vinylidene fluoride) (PVDF) membranes by phase inversion method, N,N-dimethylacetamide (DMAc) and water were used as solvent and coagulant, respectively, the role of...

Abstract  A method was investigated in which all of the phthalate esters in biological samples were determined as phthalic acid by gas-liquid chromatography. The method is based on the separation of phthalate esters from the sample with n-hexane, saponification of the esters with an alkaline ethanolic solution to give phthalic acid, purification of the acid by extraction with diethyl ether and column chromatography using silica gel, and conversion of the acid into bis(2,2,2-trifluoroethyl) phthalate with a 2,2,2-trifluoroethanol solution containing boron trifluoride. The derivative obtained is highly sensitive to an electron-capture detector, giving a sensitivity of 0.1 pg. Biological samples fortified with di(2-ethylhexyl) phthalate at levels of 5-100 ppb were analyzed, with recoveries of 70-100%

Abstract  Human exposure to acrylonitrile (ACN), a carcinogen in rats, may occur in industrial settings, through waste water and tobacco smoke. ACN is an electrophilic compound and binds covalently to nucleophilic sites in macromolecules. Measurements of adducts with hemoglobin could be utilized for improved exposure assessments. In this study, a method for quantification of N-(2-cyanoethyl)valine (CEVal), the product of reaction of ACN with N-terminal valine in hemoglobin has been developed. The method is based on the N-alkyl Edman procedure, which involves derivatization of the globin with pentafluorophenyl isothiocyanate and gas chromatographic-mass spectrometric analysis of the resulting thiohydantoin. An internal standard was prepared by reacting valylglycylglycine with [2H3]ACN, spiked with [14C]ACN to a known sp. act. Levels of CEVal were measured in globin from rats exposed to 3-300 p.p.m. ACN in drinking water for 105 days and from humans (four smokers and four non-smokers). CEVal was detected at all exposure levels in the drinking water study. The relationship between adduct level and water concentration was linear at concentrations of 10 p.p.m. (corresponding to an average daily uptake of c. 0.74 mg ACN/kg body wt during the 65 days prior to sacrifice) and below, with a slope of 37.7 pmol CEVal/g globin/p.p.m. At higher concentrations, adduct levels increased sublinearly, indicating saturation of a metabolic process for elimination of ACN. Comparison of adduct formation with the estimated dose (mg/kg/day) of ACN indicated that at low dose (0-10 p.p.m.) CEVal = 0.508 x ACN dose + 0.048 and at high dose (35-300 p.p.m.) CEVal = 1.142 x ACN dose - 1.098. Globin from the smokers (10-20 cigarettes/day) contained about 90 pmol CEVal/g, whereas the adduct levels in globin from non-smokers were below the detection limit. The analytical sensitivity should be sufficient to allow monitoring of occupationally exposed workers at levels well below the current Occupational Safety and Health Administration standard of 2 p.p.m.

Abstract  The gasotransmitter hydrogen sulfide is known to regulate multiple cellular functions during normal and pathophysiological states. However, a paucity of concise information exists regarding quantitative amounts of hydrogen sulfide involved in physiological and pathological responses. This is primarily due to disagreement among various methods employed to measure free hydrogen sulfide. In this article, we describe a very sensitive method of measuring the presence of H₂S in plasma down to nanomolar levels, using monobromobimane (MBB). The current standard assay using methylene blue provides erroneous results that do not actually measure H₂S. The method presented herein involves derivatization of sulfide with excess MBB in 100 mM Tris-HCl buffer (pH 9.5, 0.1 mM DTPA) for 30 min in 1% oxygen at room temperature. The fluorescent product sulfide-dibimane (SDB) is analyzed by RP-HPLC using an eclipse XDB-C18 (4.6 × 250 mm) column with gradient elution by 0.1% (v/v) trifluoroacetic acid in acetonitrile. The limit of detection for sulfide-dibimane is 2 nM and the SDB product is very stable over time, allowing batch storage and analysis. In summary, our MBB method is suitable for sensitive quantitative measurement of free hydrogen sulfide in multiple biological samples such as plasma, tissue and cell culture lysates, or media.

Abstract  The use of hydrochlorofluorocarbons (HCFCs) such as HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane) and HCFC-141b (1,1-dichloro-1-fluoroethane) is becoming widespread as replacements for the ozone depleting chlorofluorocarbons. Hepatic activation of HCFC-123 or the unsaturated perchloroethylene through oxidative pathways leads to the formation of the electrophiles trifluoroacetyl chloride or trichloroacetyl chloride, respectively. These can react with epsilon-NH(2) functions of lysine in proteins and give rise to neoantigens. In the case of HCFC-123, this reaction is catalysed primarily by CYP2E1 and to a much lesser extent by the constitutive CYP2C19, CYP2B6 and CYP2C8. For perchloroethylene, the extent of activation is less and the reaction is catalysed primarily by the CYP2B family. While acute hepatotoxicity has been seen in humans exposed to HCFC-123 or halothane, little short- or long-term toxicity in rodents is observed. No immunological related toxicity of perchloroethylene has been reported in exposed humans. Long-term exposure of rats can lead to renal tubule carcinomas and in mice, hepatocellular carcinomas. These toxic reactions do not appear to be directly related to the formation of the putative trichloroacetyl chloride intermediate.

Abstract  A variety of indoles underwent enantioselective Friedel-Crafts alkylation with alpha,beta-unsaturated acyl phosphonates in the presence of 10 mol% chiral BINOL-based phosphoric acid and subsequent treatment with methanol and DBU to give methyl 3-(indol-3-yl)propanoates in good yields and with high enantioselectivities.

Abstract  Haloacetic acid (HAA) concentrations were measured in air samples from a semi-rural and a highly urbanized site in southern Ontario throughout 2000 to investigate their sources and gas-particle partitioning behavior. Denuders were efficient for collection of gaseous HAAs, and the particle phase was collected on a downstream quartz filter with negligible breakthrough. Total HAA concentrations (i.e., gas + particles) ranged between <0.025 and 19 ng m(-3) for individual HAAs at both sites. The dominant airborne HAA was monochloroacetic acid (MCA), followed in decreasing order by dichloroacetic acid (DCA), trifluoroacetic acid (TFA), and trichloroacetic acid (TCA). Difluoroacetic acid (DFA), monofluoroacetic acid (MFA), and chlorodifluoroacetic acid (CDFA) were also frequently detected at lower concentrations. Between sites, TFA, DFA, MFA, and TCA concentrations were significantly higher in Toronto, while CDFA concentrations were higher in Guelph. HAAs were primarily in the gas phase all year; however, during colder months, particle-phase HAA concentrations increased relative to the gas phase. Trichloroacetic acid had the highest particle fraction (phi) for all detected HAAs, with a mean phi of 0.51 and 0.56 for Guelph and Toronto, respectively, and both vapor pressure and acid strength appeared to influence gas-particle partitioning. Temporal trends at both sites were partially explained by temperature, short-wave radiation, and particle mass (PM10), leading to indications of the respective sources. A simple deposition model indicated that dry deposition of TFA and TCA should not be neglected in temperate mid-latitude environments and that precipitation concentrations can be successfully predicted by the Henry's law constant.

Abstract  The specific features of balanced anesthesia utilizing sevoflurane (versus isoflurane) during thoracic operations under artificial one-lung ventilation (AOL ) have been studied in patients at high operative and anesthetic risks. Unlike isoflurane, sevflurane fails to cause vasodilatation in both the greater and lesser circulation (including in the gas-exchange part ofpulmonary circulation). The difference of the anesthetics in their vasodilating capacity in the vessels of pulmonary and systemic circulation determines various mechanisms of pathophysiological and adaptive circulatory changes in pulmonary collapse and under AOL V Under sevoflurane anesthesia, compensatory blood flow limitation along the collaborated lung due to permanently vasohypertension in gas-exchange microcirculation is accompanied by a systemic circulatory response that is aimed at reducing right ventricular load. Termination of hypoxic pulmonary vasoconstriction in the collaborated lung occurs not early than 80-125 min of AOLV, fails to lead to recovery of impaired gas exchange due to vasohypertension and high shunt in the ventilated lung, and is attended by right ventricular overload. The latter differentiates sevoflurane anesthesia from isoflurane one wherein completion of pulmonary hypoxic vasoconstriction upon 80-125-min exposure to AOL V results in the recovery of gas exchange to the baseline levels. The pattern of reperfusion changes in ventilation emergence in the operated lung under anesthesia using both sevoflurane and isoflurane is of no significant pathological tinge and it is followed by no pulmonary and systemic metabolic disturbances. Isoflurane should be recognized to be preferable component at the stage of anesthesia maintenance in patients with cardiopulmonary diseases during thoracic operations under prolonged AOL V (more than 2 hours).

Abstract  A denuder-filter sampling technique for the simultaneous collection of gas and particle phase carbonyl compounds has been developed and tested. The denuder was coated with XAD-4 resin and the derivatizing agent O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) to enable on-tube conversion of gas-phase carbonyls to their oxime derivatives which were extracted and identified by GC-MS. The performance of the PFBHA-coated denuder was tested on a range of carbonyls, dicarbonyls, aromatic aldehydes, carbonyl-containing furans, and benzoquinones. The collection efficiency of the PFBHA-coated denuder was over 90% for sampling times of 10 min and significantly higher than when using only XAD-4 as the sorbent. The collection efficiency and rate of on-tube derivatization was highest for aldehydes and lowest for ketones, consistent with the expected reactivity of carbonyls with PFBHA. The method was used to separate the gas and particle phase carbonyl products formed during the photooxidation of toluene in order to assess its potential for application to simulation chamber experiments of VOC oxidation. The results indicate that when compared to a conventional filter sampling setup, the PFBHA-coated denuder-filter reduced the extent of gas phase adsorption onto the filter by at least a factor of 2 for each of the carbonyls formed. Further potential applications of the denuder-filter sampling method are discussed.

Abstract  #311 chemicals were tested under code, for mutagenicity, in Salmonella typhimurium; 35 of the chemicals were tested more than once in the same or different laboratories. The tests were conducted using a preincubation protocol in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. Some of the volatile chemicals were also tested in desiccators. A total of 120 chemicals were mutagenic or weakly mutagenic, 3 were judged questionable, and 172 were non-mutagenic. The remaining 16 chemicals produced different responses in the two or three laboratories in which they were tested. The results and data from these tests are presented.

Abstract  OBJECTIVE: Study on the of content variety of flavonoids in the course of processing Cortex Moutan,and discuss the preparation mechanism of Cortex Moutan Carbonisatum (CMC). METHOD: HPLC method was developed for the determination of flavonoids in various extent of CMC, the sample was extracted by ultrasound 30 min twice along with ethanol 50 mL. Chromatographic conditions were as follows: wavelength 360 nm, gradient eluant of methanol--0.5% per hundred trifluoroacetic acid. RESULT: The content of the three flavonoids cuts down along with the processing time and the rising temperature. CONCLUSION: The impact of various extent of processing on flavonoids content of the CMC is very great. The overall trend is that high temperature and long time lead to the lower of the content of flavonoids. This provides a basis data for the further study on the hemostatic mechanism and quality control of CMC.

Abstract  The zwitterionic betaine ligand in combination with the weakly coordinating bis(trifluoromethylsulfonyl)imide anion gives rise to the formation of metal complexes with a rich structural chemistry. Polynuclear complexes are formed for the cobalt(II), nickel(II), manganese(II), zinc(II), silver(I), and lead(II) compounds.

Abstract  The reactions between metal (Pb or Bi) clusters formed by laser ablation and hexafluorobenzene (C6F6) seeded in argon carrier gas were studied by a reflectron time-of-flight mass spectrometer combined with a photoelectron spectrometer. The adiabatic electron affinities of the dominant anionic products, PbmC6F5− and BimC6F5− (m = 1−4) complexes, were obtained from the photoelectron spectra with 193 nm photons. It was found that the EAs of PbmC6F5 are higher than those of the pure Pbm clusters and that the photoelectron spectra of BimC6F5− show some similarities to those of Bim+1−. Theoretical calculations were carried out to elucidate their geometric structures and bonding modes. The adiabatic detachment energy and simulated spectrum based on Koopmans’ theorem for the optimized structures of each complex were in agreement with the photoelectron spectroscopy results. The most likely structures for each species were obtained. The analysis of the molecular orbital composition provides evidence that the C6F5 group contributes a single electron to bind with metal clusters through the M−C σ bond.

Abstract  Five new, unsymmetrical 1,4-distyryl-2,5-bisphenylethynylbenzenes (cruciforms, XF) have been prepared by a sequential Horner reaction of the bisphosphonate of 2,5-diiodo-1,4-xylene with two different aromatic aldehydes. The obtained diiodide was coupled to phenylacetylene under Sonogashira conditions with (Ph3P)2PdCl2 as catalyst. The resulting XFs carry dibutylamino, pyridyl, cyano, and diphenylamino residues on their styryl arms to give rise to donor−, acceptor−, and donor−acceptor-substituted XFs. The optical properties of these XFs were investigated. Titration studies using trifluoroacetic acid tracked changes in the electronic structure of the XFs upon protonation. Donor XFs display a blue shift in absorption and emission upon protonation, while the pyridyl-substituted XF displays red shift in absorption and emission upon protonation. In the case of the donor−acceptor XF carrying a pyridyl and an aminostyryl arm, the first protonation occurs either on the pyridine or on the dibutylamino arm; a red shift is seen in absorption (for the former) and a blue shift is observed in emission (for the latter). The titration studies indicate that the protonated XFs do not display kinetic photoacidity when operating either in dichloromethane or acetonitrile solutions. The trends observed for protonation were mirrored when the XFs bind to metal cations. While the binding constants of the metal cations to the XFs were lower than for that for protons, as in some cases full metalation of the XF could not be obtained, the results were qualitatively the same. We did not find dynamic excited-state decomplexation events in the XFs that we have investigated. The XFs, stilbene derivatives, are different from other reported, similarly structured fluorophores as they show significant ratiometric changes in emission upon metal complexation; thus, distyrylbenzene-derived fluorophores may be, in the end, viable choices as platforms for metal ion detection.

Abstract  Drug-induced respiratory depression is a common side effect of the agents used in anesthesia practice to provide analgesia and sedation. Depression of the ventilatory drive in the spontaneously breathing patient can lead to severe cardiorespiratory events and it is considered a primary cause of morbidity. Reliable predictions of respiratory inhibition in the clinical setting would therefore provide a valuable means to improve the safety of drug delivery. Although multiple studies investigated the regulation of breathing in man both in the presence and absence of ventilatory depressant drugs, a unified description of respiratory pharmacodynamics is not available. This study proposes a mathematical model of human metabolism and cardiorespiratory regulation integrating several isolated physiological and pharmacological aspects of acute drug-induced ventilatory depression into a single theoretical framework. The description of respiratory regulation has a parsimonious yet comprehensive structure with substantial predictive capability. Simulations relative to the synergistic interaction of the hypercarbic and hypoxic respiratory drive and the global effect of drugs on the control of breathing are in good agreement with published experimental data. Besides providing clinically relevant predictions of respiratory depression, the model can also serve as a test bed to investigate issues of drug tolerability and dose finding/control under non-steady-state conditions.