Gas-phase reactivity of protonated 2-oxazoline derivatives: mass spectrometry and computational studies

RATIONALE: Oxazolines have attracted the attention of researchers worldwide due to their versatility as carboxylic acid protecting groups, chiral auxiliaries, and ligands for asymmetric catalysis. Electrospray ionization tandem mass spectrometric (ESI-MS/MS) analysis of five 2-oxazoline derivatives has been conducted, in order to understand the influence of the side chain on the gas-phase dissociation of these protonated compounds under collision-induced dissociation (CID) conditions. METHODS: Mass spectrometric analyses were conducted in a quadrupole time-of-flight (Q-TOF) spectrometer fitted with electrospray ionization source. Protonation sites have been proposed on the basis of the gas-phase basicity, proton affinity, atomic charges, and a molecular electrostatic potential map obtained on the basis of the quantum chemistry calculations at the B3LYP/6-31 + G(d, p) and G2(MP2) levels. RESULTS: Analysis of the atomic charges, gas-phase basicity and proton affinities values indicates that the nitrogen atom is a possible proton acceptor site. On the basis of these results, two main fragmentation processes have been suggested: one taking place via neutral elimination of the oxazoline moiety (99 u) and another occurring by sequential elimination of neutral fragments with 72 u and 27 u. These processes should lead to formation of R+. CONCLUSIONS: The ESI-MS/MS experiments have shown that the side chain could affect the dissociation mechanism of protonated 2-oxazoline derivatives. For the compound that exhibits a hydroxyl at the lateral chain, water loss has been suggested to happen through an E2-type elimination, in an exothermic step. Copyright (C) 2012 John Wiley & Sons, Ltd.

Gas-phase reactivity of 2-hydroxy-1,4-naphthoquinones: a computational and mass spectrometry study of lapachol congeners

In order to understand the influence of alkyl side chains on the gas-phase reactivity of 1,4-naphthoquinone derivatives, some 2-hydroxy-1,4-naphthoquinone derivatives have been prepared and studied by electrospray ionization tandem mass spectrometry in combination with computational quantum chemistry calculations. Protonation and deprotonation sites were suggested on the basis of gas-phase basicity, proton affinity, gas-phase acidity (?Gacid), atomic charges and frontier orbital analyses. The nature of the intramolecular interaction as well as of the hydrogen bond in the systems was investigated by the atoms-in-molecules theory and the natural bond orbital analysis. The results were compared with data published for lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone). For the protonated molecules, water elimination was verified to occur at lower proportion when compared with side chain elimination, as evidenced in earlier studies on lapachol. The side chain at position C(3) was found to play important roles in the fragmentation mechanisms of these compounds. Copyright (c) 2012 John Wiley & Sons, Ltd.

Hb S-Sao Paulo: A new sickling hemoglobin with stable polymers and decreased oxygen affinity

Hb S-Sao Paulo (SP) [HBB:c.20A > T p.Glu6Val: c.196A > G p.Lys65Glu] is a new double-mutant hemoglobin that was found in heterozygosis in an 18-month-old Brazilian male with moderate anemia. It behaves like Hb S in acid electrophoresis, isoelectric focusing and solubility testing but shows different behavior in alkaline electrophoresis, cation-exchange HPLC and RP-HPLC. The variant is slightly unstable, showed reduced oxygen affinity and also appeared to form polymers more stable than the Hb S. Molecular dynamics simulation suggests that the polymerization is favored by interfacial electrostatic interactions. This provides a plausible explanation for some of the reported experimental observations. (C) 2012 Elsevier Inc. All rights reserved.

Electrostatic potentials and polarization effects in proton-molecule interactions by means of multipoles from the quantum theory of atoms in molecules

Some atomic multipoles (charges, dipoles and quadrupoles) from the Quantum Theory of Atoms in Molecules (QTAIM) and CHELPG charges are used to investigate interactions between a proton and a molecule (F2, Cl2, BF, AlF, BeO, MgO, LiH, H2CO, NH3, PH3, BF3, and CO2). Calculations were done at the B3LYP/6-311G(3d,3p) level. The main aspect of this work is the investigation of polarization effects over electrostatic potentials and atomic multipoles along a medium to long range of interaction distances. Large electronic charge fluxes and polarization changes are induced by a proton mainly when this positive particle approaches the least electronegative atom of diatomic heteronuclear molecules. The search for simple equations to describe polarization on electrostatic potentials from QTAIM quantities resulted in linear relations with r-4 (r is the interaction distance) for many cases. Moreover, the contribution from atomic dipoles to these potentials is usually the most affected contribution by polarization what reinforces the need for these dipoles to a minimal description of purely electrostatic interactions. Finally, CHELPG charges provide a description of polarization effects on electrostatic potentials that is in disagreement with physical arguments for certain of these molecules. (c) 2012 Wiley Periodicals, Inc.

Comparative study of the proton beam effects between the conventional and Circular-Gate MOSFETs

The study of ionizing radiation effects on semiconductor devices is of great relevance for the global technological development and is a necessity in some strategic areas in Brazil. This work presents preliminary results of radiation effects in MOSFETs that were exposed to 3.2 Grad radiation dose produced by a 2.6-MeV proton beam. The focus of this work was to electrically characterize a Rectangular-Gate MOSFET (RGT) and a Circular-Gate MOSFET (CGT), manufactured with the On Semiconductor 0.5 mu m standard CMOS fabrication process and to verify a suitable geometry for space applications. During the experiment, I-DS x V-GS curves were measured. After irradiation, the RGT off-state current (I-OFF) increased approximately two orders of magnitude reaching practically the same value of the I-OFF in the CGT, which only doubled its value. (C) 2011 Elsevier B.V. All rights reserved.

Performance of electronic devices submitted to X-rays and high energy proton beams

In this work we have studied the radiation effects on MOSFET electronic devices. The integrated circuits were exposed to 10 key X-ray radiation and 2.6 MeV energy proton beam. We have irradiated MOSFET devices with two different geometries: rectangular-gate transistor and circular-gate transistor. We have observed the cumulative dose provokes shifts on the threshold voltage and increases or decreases the transistor's off-state and leakage current. The position of the trapped charges in modern CMOS technology devices depends on radiation type, dose rate, total dose, applied bias and is a function of device geometry. We concluded the circular-gate transistor is more tolerant to radiation than the rectangular-gate transistor. (C) 2011 Elsevier B.V. All rights reserved.

The Li-8(p, alpha)He-5 reaction at low energies, and Be-9 spectroscopy around the proton threshold

We present a direct measurement of the low-energy Li-8(p, alpha)He-5 cross section, using a radioactive Li-8 beam impinging on a thick target. With four beam energies, we cover the energy range between E-c.m. = 0.2 and 2.1 MeV. An R-matrix analysis of the data is performed and suggests the existence of two broad overlapping resonances (5/2(+) at E-c.m. = 1.69 MeV and 7/2(+) at E-c.m. = 1.76 MeV). At low energies our data are sensitive to the properties of a subthreshold state (E-x = 16.67 MeV) and of two resonances above threshold. These resonances were observed in previous experiments. The R-matrix fit confirms spin assignments, and provides partial widths. We propose a new Li-8(p, alpha)He-5 reaction rate and briefly discuss its influence in nuclear astrophysics. DOI: 10.1103/PhysRevC.86.064321

Neutral pion and eta meson production in proton-proton collisions at root s=0.9 TeV and root s=7 TeV

The first measurements of the invariant differential cross sections of inclusive pi(0) and eta meson production at mid-rapidity in proton-proton collisions root s = 0.9 TeV and root s = 7 TeV are reported. The pi(0) measurement covers the ranges 0.4 < p(T) < 7 GeV/c and 0.3 < p(T) < 25 GeV/c for these two energies, respectively. The production of eta mesons was measured at root s = 7 TeV in the range 0.4 < p(T) < 15 GeV/c. Next-to-Leading Order perturbative QCD calculations, which are consistent with the pi(0) spectrum at root s = 0.9 TeV, overestimate those of pi(0) and eta mesons at root s = 7 TeV, but agree with the measured eta/pi(0) ratio at root s = 7 TeV. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.

Jacalin interaction with human immunoglobulin A1 and bovine immunoglobulin G1: Affinity constant determined by piezoelectric biosensoring

The affinity of the d-galactose-binding lectin from Artocarpus heterophyllus lectin, known as jacalin, with immonuglobulins (Igs) was determined by biofunctionalization of a piezoelectric transducer. This piezoelectric biofunctionalized transducer was used as a mass-sensitive analytical tool, allowing the real-time binding analysis of jacalin-human immunoglobulin A1 (IgA(1)) and jacalin-bovine IgG(1) interactions from which the apparent affinity constant was calculated. The strategy was centered in immobilizing jacalin on the gold electrode's surface of the piezoelectric crystal resonator using appropriate procedures based on self-assembling of 11-mercaptoundecanoic acid and 2-mercaptoethanol thiol's mixture, a particular immobilization strategy by which it was possible to avoid cross-interaction between the proteins over electrode's surface. The apparent affinity constants obtained between jacalin-human IgA(1) and jacalin-bovine IgG(1) differed by 1 order of magnitude [(8.0 +/- 0.9) x 10(5) vs (8.3 +/- 0.1) x 10(6) L mol(-1)]. On the other hand, the difference found between human IgA(1) and human IgA(2) interaction with jacalin, eight times higher for IgA(1), was attributed to the presence of O-linked glycans in the IgA(1) hinge region, which is absent in IgA(2). Specific interaction of jacalin with O-glycans, proved to be present in the human IgA(1) and hypothetically present in bovine IgG(1) structures, is discussed as responsible for the obtained affinity values.

Transverse sphericity of primary charged particles in minimum bias proton-proton collisions at root s=0.9, 2.76 and 7 TeV

Measurements of the sphericity of primary charged particles in minimum bias proton-proton collisions at root s = 0.9, 2.76 and 7 TeV with the ALICE detector at the LHC are presented. The observable is measured in the plane perpendicular to the beam direction using primary charged tracks with p(T) > 0.5 GeV/c in vertical bar eta vertical bar < 0.8. The mean sphericity as a function of the charged particle multiplicity at mid-rapidity (N-ch) is reported for events with different p(T) scales ("soft" and "hard") defined by the transverse momentum of the leading particle. In addition, the mean charged particle transverse momentum versus multiplicity is presented for the different event classes, and the sphericity distributions in bins of multiplicity are presented. The data are compared with calculations of standard Monte Carlo event generators. The transverse sphericity is found to grow with multiplicity at all collision energies, with a steeper rise at low N-ch, whereas the event generators show an opposite tendency. The combined study of the sphericity and the mean p(T) with multiplicity indicates that most of the tested event generators produce events with higher multiplicity by generating more back-to-back jets resulting in decreased sphericity (and isotropy). The PYTHIA6 generator with tune PERUGIA-2011 exhibits a noticeable improvement in describing the data, compared to the other tested generators.

Pion, Kaon, and Proton Production in Central Pb-Pb Collisions at root s(NN)=2.76 TeV

In this Letter we report the first results on pi(+/-), K-+/-, p, and (p) over bar production at midrapidity (vertical bar y vertical bar < 0.5) in central Pb-Pb collisions at root s(NN) = 2.76 TeV, measured by the ALICE experiment at the LHC. The p(T) distributions and yields are compared to previous results at root s(NN) = 200 GeV and expectations from hydrodynamic and thermal models. The spectral shapes indicate a strong increase of the radial flow velocity with root s(NN), which in hydrodynamic models is expected as a consequence of the increasing particle density. While the K/pi ratio is in line with predictions from the thermal model, the p/pi ratio is found to be lower by a factor of about 1.5. This deviation from thermal model expectations is still to be understood.

Influence of 60-MeV Proton-Irradiation on Standard and Strained n- and p-Channel MuGFETs

In this work the proton irradiation influence on Multiple Gate MOSFETs (MuGFETs) performance is investigated. This analysis was performed through basic and analog parameters considering four different splits (unstrained, uniaxial, biaxial, uniaxial+biaxial). Although the influence of radiation is more pronounced for p-channel devices, in pMuGFETs devices, the radiation promotes a higher immunity to the back interface conduction resulting in the analog performance improvement. On the other hand, the proton irradiation results in a degradation of the post-irradiated n-channel transistors behavior. The unit gain frequency showed to be strongly dependent on stress efficiency and the radiation results in an increase of the unit gain frequency for splits with high stress effectiveness for both cases p- and nMuGFETs.

D-S(+) meson production at central rapidity in proton-proton collisions at root s=7 TeV

The P-T-differential inclusive production cross section of the prompt charm-strange meson D-s(+) in the rapidity range vertical bar y vertical bar < 0.5 was measured in proton-proton collisions at root s = 7 TeV at the LHC using the ALICE detector. The analysis was performed on a data sample of 2.98 x 10(8) events collected with a minimum-bias trigger. The corresponding integrated luminosity is L-int = 4.8 nb(-1). Reconstructing the decay D-s(+) -> phi pi(+) with phi -> K-K+, and its charge conjugate, about 480 D-s(+/-) mesons were counted, after selection cuts, in the transverse momentum range 2 < P-T < 12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D-0, D+, D*+ and D-s(+)) were determined both as a function of p(T) and integrated over p(T)after extrapolating to full p(T) range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e(+)e(-), ep and pp interactions at various centre-of-mass energies. (C) 2012 CERN. Published by Elsevier By. All rights reserved.

Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor Insights From the Platelet Inhibition and Patient Outcomes Trial

Background-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n = 6539) compared with those not on a PPI (n = 12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49). Conclusions-The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.

A fragment-based approach for ligand binding affinity and selectivity for the liver X receptor beta

Selective modulation of liver X receptor beta (LXR beta) has been recognized as an important approach to prevent or reverse the atherosclerotic process. In the present work, we have developed robust conformation-independent fragment-based quantitative structure-activity and structure-selectivity relationship models for a series of quinolines and cinnolines as potent modulators of the two LXR sub-types. The generated models were then used to predict the potency of an external test set and the predicted values were in good agreement with the experimental results, indicating the potential of the models for untested compounds. The final 2D molecular recognition patterns obtained were integrated to 3D structure-based molecular modeling studies to provide useful insights into the chemical and structural determinants for increased LXR beta binding affinity and selectivity. (C) 2011 Elsevier Inc. All rights reserved.