Lifetime study of high-spin states in 104,105In

In the neutron deficient isotopes _104,105In lifetimes of high spin states in the range from 0.5 ps to 600 ps have been measured in a coincidence recoil distance Doppler shift (RDDS) experiment. By combining the Doppler shift attenuation (DSA) and RDDS methods at few μm flight distances, the problem of delayed feeding has been avoided and very short lifetimes in the range 0.5–0.8 ps have been determined. Shell model calculations with strong restrictions for the neutron orbitals reveal good agreement with experimental level energies and still fair agreement for most measured B(M1) and B(E2) values. Received: 30 June 1998     

Isochorismate pyruvate lyase: a pericyclic reaction mechanism?

Isochorismate pyruvate lyase (IPL) catalyzes the cleavage of isochorismate to give salicylate and pyruvate, a key step in bacterial siderophore biosynthesis. We investigated the enzyme from Pseudomonas aeruginosa using isochorismate selectively deuterated at C2 as a substrate. Monitoring the reaction by 2H NMR spectroscopy revealed that the label is quantitatively transferred from C2 to C9, producing stoichiometric amounts of [3-2H]pyruvate as product. Moreover, the deuterium kinetic isotope effect of 2.34 +/- 0.08 on kcat indicates that C-H cleavage is significantly rate limiting. Consistent with these data, hybrid density functional theory (HDFT) calculations at the Becke3LYP/DZ+(2d,p) level of theory predict a concerted but highly asynchronous pericyclic transition structure, in which carbon-oxygen bond cleavage is more advanced than hydrogen atom transfer from C2 to C9; the calculated 2H isotope effect of 2.22 at C2 is in excellent accord with the experimental value. Together, these findings indicate that IPL should be added to the small set of proteins that are known to catalyze pericyclic reactions. They also raise the possibility that enzymes, such as chorismate pyruvate lyase, salicylate synthase, 4-amino-4-deoxychorismate lyase, and anthranilate synthase, which accelerate formally similar reaction steps, may also exploit pericyclic mechanisms.     

Diffusion mit überlagerter reibungsbehafteter Strömung

Zusammenfassung Es wird eine allgemeine Differentialgleichung für den Massen- oder Mengenstrom im Fall einer Überlagerung von Diffusion und reibungsbehafteter Strömung, d.h. bei gleichzeitiger Änderung des Gesamtdruckes und der Partialdrücke über den Weg, für den stationären (und quasistationären) Fall abgeleitet. Die sich ergebenden gekoppelten Differentialgleichungen können näherungsweise analytisch gelöst werden.Bei den Überlagerungen wurde allein von Gas-(Fickscher) Diffusion ausgegangen. Unberücksichtigt blieben auch sekundäre Diffusionströme, so durch Druck- u. Thermodiffusion und in anderen Kraftfeldern. Damit wird an zwei Beispielen — einseitige Diffusion (Verdunstung) und Adsorption in porösen Stoffen — gezeigt, daß die Annahme reibungsfreier konvektiver Ausgleichsströmungen bei der Diffusion in porösen Körpern mit engen Poren nicht zulässig ist. Vielmehr treten am Ort der Entstehung des Diffusionsstromes (Verdunstungsspiegel) bzw. in der Adsorptionsfront Änderungen des Gesamtdruckes auf, die zu zusätzlichen Strömungen führen und Rückwirkungen auf den Massenstrom besitzen. Neben der Höhe der Konzentrationen ist für die Größe des Effektes allein das Verhältnis der Transportkoeffizienten für Strömung und Diffusion maßgebend. Der Effekt macht sich bei hohen Konzentrationen der diffundierenden Komponente deutlich bemerkbar, bei niedrigen ist er — wie zu erwarten — zu vernachlässigen.

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Diffusion of superimposed frictional flow

A general differential equation for a mass and volume flow will be derived for the case of diffusion superimposed frictional flow, that means, at simultaneously varying total and partial pressures along the path, for the stationary and quasi-stationary states. The resulting coupled differential equations can be analytically treated for an approximate solution.The conception was based entirely upon (Fick's) gas diffusion. Secondary diffusional flows were neglected, like pressure and thermal diffusions, or those caused by other potential gradients. Two examples, the diffusion through a stagnant gas film (evaporation by diffusion), and the adsorption in porous material exemplify that assuming a frictionless convective arbitration flow is invalid in the case of diffusion within porous structures of narrow pores. Adequately, at the source of the diffusional flow (mirror of diffusional evaporation), respectively within the adsorption front, changes in total pressure arise, causing additional flows acting upon the mass flow. The scope of the effect depends entirely upon the extents of the concentration and the ratio of transport coefficients of the flow and diffusion. The effect increases noticeably at elevated concentration of the diffusing components, while it gets negligible at lower concentration, as to be expected.

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Formelzeichen c Konzentration [kmol/m³] - d _p Porendurchmesser - bezogener Diffusionsstrom - f Querschnittsfläche - bezogener Strom - M relative Molmasse - Mengenstromdichte - P Druck - R _a Radius eines kugelförmigen Partikels - s Diffusionsweg - t Zeit - v Geschwindigkeit des konv. Stroms - w _Fr Frontgeschwindigkeit - x Variable des Weges - X Beladung des Adsorbens [kmol/kg] - Z, z Variable, s. Gl. (23), Gl. (29) Griechische Buchstaben (X) Kapazitätsfaktor - Verhältnis der Transportkoeffizienten _lam/ _D - Diffusions- bzw. äquivalenter Transportkoeffizient - freie Weglänge - dynamische Zähigkeit - Tortuositätsfaktor - Dichte - Lage der Adsorptionsfront - Porosität des Adsorbens Indices o Bezugsgröße bzw. vorgegebener Wert der Größe im Gas - e einseitig - D Dampf, diffundierende Komponente - L Luft, aufnehmendes Gas - lam laminare Strömung - s Feststoff - in der Adsorptionsfront     

Prediction of tautomer ratios by embedded-cluster integral equation theory

The “embedded cluster reference interaction site model” (EC-RISM) approach combines statistical-mechanical integral equation theory and quantum-chemical calculations for predicting thermodynamic data for chemical reactions in solution. The electronic structure of the solute is determined self-consistently with the structure of the solvent that is described by 3D RISM integral equation theory. The continuous solvent-site distribution is mapped onto a set of discrete background charges (“embedded cluster”) that represent an additional contribution to the molecular Hamiltonian. The EC-RISM analysis of the SAMPL2 challenge set of tautomers proceeds in three stages. Firstly, the group of compounds for which quantitative experimental free energy data was provided was taken to determine appropriate levels of quantum-chemical theory for geometry optimization and free energy prediction. Secondly, the resulting workflow was applied to the full set, allowing for chemical interpretations of the results. Thirdly, disclosure of experimental data for parts of the compounds facilitated a detailed analysis of methodical issues and suggestions for future improvements of the model. Without specifically adjusting parameters, the EC-RISM model yields the smallest value of the root mean square error for the first set (0.6 kcal mol⁻¹) as well as for the full set of quantitative reaction data (2.0 kcal mol⁻¹) among the SAMPL2 participants.     

The SAMPL5 challenge for embedded-cluster integral equation theory: solvation free energies,aqueous p<Emphasis Type="Italic">K</Emphasis><Subscript>a</Subscript>, and cyclohexane–water log <Emphasis Type="Italic">D</Emphasis>

We predict cyclohexane–water distribution coefficients (log D _7.4) for drug-like molecules taken from the SAMPL5 blind prediction challenge by the “embedded cluster reference interaction site model” (EC-RISM) integral equation theory. This task involves the coupled problem of predicting both partition coefficients (log P) of neutral species between the solvents and aqueous acidity constants (pK _a) in order to account for a change of protonation states. The first issue is addressed by calibrating an EC-RISM-based model for solvation free energies derived from the “Minnesota Solvation Database” (MNSOL) for both water and cyclohexane utilizing a correction based on the partial molar volume, yielding a root mean square error (RMSE) of 2.4 kcal mol^?1 for water and 0.8–0.9 kcal mol^?1 for cyclohexane depending on the parametrization. The second one is treated by employing on one hand an empirical pK _a model (MoKa) and, on the other hand, an EC-RISM-derived regression of published acidity constants (RMSE of 1.5 for a single model covering acids and bases). In total, at most 8 adjustable parameters are necessary (2–3 for each solvent and two for the pK _a) for training solvation and acidity models. Applying the final models to the log D _7.4 dataset corresponds to evaluating an independent test set comprising other, composite observables, yielding, for different cyclohexane parametrizations, 2.0–2.1 for the RMSE with the first and 2.2–2.8 with the combined first and second SAMPL5 data set batches. Notably, a pure log P model (assuming neutral species only) performs statistically similarly for these particular compounds. The nature of the approximations and possible perspectives for future developments are discussed.     

Mass spectrometric characterization of lipid-modified peptides for the analysis of acylated proteins

The analysis of acylated proteins by mass spectrometry (MS) has largely been overshadowed in proteomics by the analysis of glycosylated and phosphorylated proteins; however, lipid modifications on proteins are proving to be of increasing importance in biomedical research. In order to identify the marker ions and/or neutral loss fragments that are produced upon collision-induced dissociation, providing a means to identify the common lipid modifications on proteins, peptides containing an N-terminally myristoylated glycine, a palmitoylated cysteine and a farnesylated cysteine were chemically synthesized. Matrix-assisted laser desorption/ionization time-of-flight time-of-flight (MALDI-TOF-TOF), electrospray ionization quadrupole time-of-flight (ESI Q-TOF), and electrospray ionization hybrid triple-quadrupole/linear ion trap (ESI QqQ(LIT)) mass spectrometers were used for the analysis. The peptide containing the N-terminally myristoylated glycine, upon CID, produced the characteristic fragments a1 (240.4 Th) and b1 (268.4 Th) ions as well as a low-intensity neutral loss of 210 Da (C14H26O). The peptides containing a farnesylated cysteine residue fragmented to produce a marker ion at a m/z of 205 Th (C15H25) as well as other intense farnesyl fragment ions, and a neutral loss of 204 Da (C15H24). The peptides containing a palmitoylated cysteine moiety generated neutral losses of 238 Da (C16H30O) and 272 Da (C16H32OS); however, no marker ions were produced. The neutral losses were more prominent in the MALDI-TOF-TOF spectra, whereas the marker ions were more abundant in the ESI QqQ(LIT) and Q-TOF mass spectra.