Search for doubly charged Higgs bosons decaying to dileptons in pp collisions at square root of s=1.96 TeV

We present the results of a search for doubly charged Higgs bosons (H+/-+/-) decaying to dileptons (ll(')) using approximately 240 pb(-1) of pp collision data collected by the CDF II experiment at the Fermilab Tevatron. In our search region, given by same-sign ll(') mass m(ll('))>80 GeV/c(2) (100 GeV/c(2) for ee channel), we observe no evidence for H+/-+/- production. We set limits on sigma(pp -->H++H---->l(+)l('+)l(-)l('-)) as a function of the mass of the H+/-+/- and the chirality of its couplings. Assuming exclusive same-sign dilepton decays, we derive lower mass limits on H(+/-+/-)(L) of 133, 136, and 115 GeV/c(2) in the ee, mumu, and emu channels, respectively, and a lower mass limit of 113 GeV/c(2) on H(+/-+/-)(R) in the mumu channel, all at the 95% confidence level.     

A tandem Diels–Alder/Mannich approach to the synthesis of AE and ABE ring analogues of Delphinium alkaloids

The one-pot TiCl₄ catalysed Diels–Alder/Mannich reaction of α-cyanoaminoacrylates with 2-silyloxy-1,4-butadienes gives 6-keto-3-azabicyclo[3.3.1]nonane-1-carboxylates. Reduction of the ketone and alkylation of the resultant alcohol gives 6-alkoxy-3-azabicyclo[3.3.1]nonanes mimicking the AE rings of a number of Delphinium and Aconitum alkaloids, with the same stereochemistry as the natural products.     

Scaffold hopping using clique detection applied to reduced graphs

Similarity-based methods for virtual screening are widely used. However, conventional searching using 2D chemical fingerprints or 2D graphs may retrieve only compounds which are structurally very similar to the original target molecule. Of particular current interest then is scaffold hopping, that is, the ability to identify molecules that belong to different chemical series but which could form the same interactions with a receptor. Reduced graphs provide summary representations of chemical structures and, therefore, offer the potential to retrieve compounds that are similar in terms of their gross features rather than at the atom-bond level. Using only a fingerprint representation of such graphs, we have previously shown that actives retrieved were more diverse than those found using Daylight fingerprints. Maximum common substructures give an intuitively reasonable view of the similarity between two molecules. However, their calculation using graph-matching techniques is too time-consuming for use in practical similarity searching in larger data sets. In this work, we exploit the low cardinality of the reduced graph in graph-based similarity searching. We reinterpret the reduced graph as a fully connected graph using the bond-distance information of the original graph. We describe searches, using both the maximum common induced subgraph and maximum common edge subgraph formulations, on the fully connected reduced graphs and compare the results with those obtained using both conventional chemical and reduced graph fingerprints. We show that graph matching using fully connected reduced graphs is an effective retrieval method and that the actives retrieved are likely to be topologically different from those retrieved using conventional 2D methods.     

Semiclassical transition state theory/master equation kinetics of HO + CO: Performance evaluation

Previously, master equation (ME) simulations using semiclassical transition state theory (SCTST) and high-accuracy extrapolated ab initio thermochemistry (HEAT) predicted rate constants in excellent agreement with published experimental data over a wide range of pressure and temperatures ≳250 K, but the agreement was not as good at lower temperatures. Possible reasons for this reduced performance are investigated by (a) critically evaluating the published experimental data and by investigating; (b) three distinct ME treatments of angular momentum, including one that is exact at the zero- and infinite-pressure limits; (c) a hindered-rotor model for HOCO that implicitly includes the cis- and trans-conformers; (d) possible empirical adjustments of the thermochemistry; (e) possible empirical adjustments to an imaginary frequency controlling tunneling; (f) including or neglecting the prereaction complex PRC1; and (g) its possible bimolecular reactions. Improvements include better approximations to factors in SCTST and using the Hill and van Vleck treatment of angular momentum coupling. Evaluation of literature data does not reveal any specific shortcomings, but the stated uncertainties may be underestimated. All ME treatments give excellent fits to experimental data at T ≥ 250 K, but the discrepancy at T < 250 K persists. Note that each ME model requires individual empirical energy transfer parameters. Thermochemical adjustments were unable to match the experimental H/D kinetic isotope effects. Adjusting an imaginary frequency can achieve good fits, but the adjustments are unacceptably large. Whether PRC1 and its possible bimolecular reactions are included had little effect. We conclude that none of the adjustments is an improvement over the unadjusted theory. Note that only one set of experimental data exists in the regime of the discrepancy with theory, and data for DO + CO are scanty.     

Analysis of partially resolved liquid chromatographic peaks using dynamic modeling with the kalman filter

Establishing a calibration model is an important part of any mathematical method for multi-component determination. Use of a calibration model based on single spectra is subject to error, because the model spectrum chosen may not be representative of the response over the full range of the calibration. Alternative calibration models require more time to establish calibration, an these may not be convenient for real-time determinations. A novel calibration method is reported for use with Kalman filters. The method, dynamic modeling, is based on the use of libraries of calibration spectra. The set of used to describe the model at any time is based on component concentrations, estimated for the multi-component mixture, as determined from the Kalman filter, so that several spectra can be used to best describe a varying response. Through application of the dynamic modelingt to simulated and real chromatograms, it is demonstrated that use of the method decreases estimation errors cause by model data mismatches, and that full benefit can be obtained from relatively small libraries.     

Self-assembly in complex mixed surfactant solutions: the impact of dodecyl triethylene glycol on dihexadecyl dimethyl ammonium bromide

The impact of the nonionic surfactant, dodecyl triethyleneglycol ether (C(12)E(3)) on the solution microstructure of the dialkyl chain cationic surfactant, dihexadecyl dimethyl ammonium bromide, (DHDAB) has been investigated. The variation in solution microstructure has been studied using a combination of small angle neutron scattering, ultra small angle neutron scattering, optical texture and photon correlation spectroscopy. At low surfactant concentrations (1.5 mM) the microstructure takes the form of bilamellar vesicles (BLV) for compositions containing less than 20 mol % of added C(12)E(3). Multilamellar vesicles (MLV) are the predominant microstructure for solutions richer in composition than 20 mol % C(12)E(3). At more than 80 mol % C(12)E(3), the solution microstructure reverts to that of a lamellar phase dispersion consistent with studies on the pure nonionic surfactant. At higher concentrations (60 mM) a wide continuous L beta phase region is observed for compositions in the range 20 to 80 mol % C(12)E(3). The fine details of the phase diagram were obtained from quantitative analysis of the SANS data using a well-established lamellar membrane model. Irrespective of the nonionic content, the bilayers are in general highly rigid, consistent with those stabilized by charge interactions. Furthermore estimates of the product of membrane moduli (compressibility and bending modulus) indicate that the different phase regions have very different membrane properties, however the magnitude of the variations observed are not predicted using existing theoretical treatments.     

Ambient ionisation mass spectrometry for the characterisation of polymers and polymer additives: A review

The purpose of this review is to showcase the present capabilities of ambient sampling and ionisation technologies for the analysis of polymers and polymer additives by mass spectrometry (MS) while simultaneously highlighting their advantages and limitations in a critical fashion. To qualify as an ambient ionisation technique, the method must be able to probe the surface of solid or liquid samples while operating in an open environment, allowing a variety of sample sizes, shapes, and substrate materials to be analysed. The main sections of this review will be guided by the underlying principle governing the desorption/extraction step of the analysis; liquid extraction, laser ablation, or thermal desorption, and the major component investigated, either the polymer itself or exogenous compounds (additives and contaminants) present within or on the polymer substrate. The review will conclude by summarising some of the challenges these technologies still face and possible directions that would further enhance the utility of ambient ionisation mass spectrometry as a tool for polymer analysis.     

On modeling the pressure-dependent photoisomerization of trans-stilbene by including slow intramolecular vibrational energy redistribution

Experimental data for the photoisomerization of trans-stilbene (S(1)) in thermal bath gases at pressures up to 20 bar obtained previously by Meyer, Schroeder, and Troe (J. Phys. Chem. A 1999, 103, 10528-10539) are modeled by using a full collisional-reaction master equation that includes non-RRKM (Rice-Ramsperger-Kassel-Marcus) effects due to slow intramolecular vibrational energy redistribution (IVR). The slow IVR effects are modeled by incorporating the theoretical results obtained recently by Leitner et al. (J. Phys. Chem. A 2003, 107, 10706-10716), who used the local random matrix theory. The present results show that the experimental rate constants of Meyer et al. are described to within about a factor of 2 over much of the experimental pressure range. However, a number of assumptions and areas of disagreement will require further investigation. These include a discrepancy between the calculated and experimental thermal rate constants near zero pressure, a leveling off of the experimental rate constants that is not predicted by theory and which depends on the identity of the collider gas, the need to use rate constants for collision-induced IVR that are larger than the estimated total collision rate constants, and the choice of barrier-crossing frequency. Despite these unsettled issues, the theory of Leitner et al. shows great promise for accounting for possible non-RRKM effects in an important class of reactions.     

LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens,their precursors,and major metabolites in rat pineal gland microdialysate

We report a qualitative liquid chromatography–tandem mass spectrometry (LC/MS/MS) method for the simultaneous analysis of the three known N,N‐dimethyltryptamine endogenous hallucinogens, their precursors and metabolites, as well as melatonin and its metabolic precursors. The method was characterized using artificial cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the analysis of rat brain pineal gland‐aCSF microdialysate. The method describes the simultaneous analysis of 23 chemically diverse compounds plus a deuterated internal standard by direct injection, requiring no dilution or extraction of the samples. The results demonstrate that this is a simple, sensitive, specific and direct approach to the qualitative analysis of these compounds in this matrix. The protocol also employs stringent MS confirmatory criteria for the detection and confirmation of the compounds examined, including exact mass measurements. The excellent limits of detection and broad scope make it a valuable research tool for examining the endogenous hallucinogen pathways in the central nervous system. We report here, for the first time, the presence of N,N‐dimethyltryptamine in pineal gland microdialysate obtained from the rat. Copyright © 2013 John Wiley & Sons, Ltd.     

Annulation of primary amines to piperazines and diazaspirocycles utilizing alpha-methyl benzyl resin

The microwave-assisted solid-phase synthesis of piperazines, 3,9-diazaspiro[5.5]undecanes and 2,9-diazaspiro[5.5]undecanes is reported. The synthesis relies on the direct annulation of primary amines with resin-bound bismesylates. Critical to the success of this chemistry was the development of alpha-methyl benzyl carbamate resin linker. This resin permits the cleavage of the heterocycles under mildly acidic conditions, free of contaminating linker-derived N-alkylated byproducts.