Engleromycin,a new cytochalasan from Engleromycesgoetzei Hennings

The structure of engleromycin isolated from $\text{Engleromyces}$$\text{goetzei}$ Hennings has been established as $\text{1}$ by spectral techniques.     

Quasiperiodic trajectories in the unimolecular dissociation of ethyl radicals by time-frequency analysis

Direct classical trajectory calculations for ethyl radical, C2H5, at the HCTH147@6-31 +G**/6-31G** level of theory support the experimental observation that the dissociation of highly excited ethyl radicals to ethylene and and a hydrogen atom can occur much more slowly than predicted by statistical rate theories. Only 78% of the trajectories of ethyl radicals prepared in a microcanonical ensemble with 120-kcal/mol excitation energy above the zero-point energy and zero total angular momentum dissociate to form C2H4 + H. The remaining hot ground-state ethyl radicals have a lifetime of >2 ps, during which a time-frequency analysis finds them trapped for extended periods of time in long-lived quasiperiodic trajectories.     

Prediction of adsorption behavior of activated carbons

A study was made of the effect of temperature on predictive equations recently developed and applied to gas adsorption by beds of activated and impregnated carbons. Adsorption parameters, obtained for the adsorbate DMMP on small gram quantities of impregnated carbon at 25°C and applied to carbon bed breakthru times, were analyzed for changes resulting from direct temperature effects on gas diffusion, adsorption—desorption equilibria, volume expansion, relative pressure, and adsorbate—adsorbent interactions. Modifications in the adsorption parameters, calculated for bed temperatures ranging between 40.3 and 46.7°C, were used in the kinetic equations to predict breakthru times for M10 gas filters, each containing 13,847 g of carbon. The predicted values compared very well with those experimentally determined, the mean deviation in breakthru time being 5.82%, without regard to sign. A general analysis of a 10°C rise in temperature, from 25 to 35°C, for the M10 gas filter under the test conditions used, showed that the breakthru time would be lowered 20.0 min, 87% of this lowering due to a reduced adsorption rate constant, 9% due to a reduced adsorption capacity, and 4% due to volume expansion effects on concentration and flowrate.     

Binding of the general anesthetics chloroform and 2,2,2-trichloroethanol to the hydrophobic core of a four-alpha-helix bundle proteins

The structural features of general anesthetic binding sites on proteins are being examined using a defined model system consisting of a four-alpha-helix bundle scaffold with a hydrophobic core. Previous work suggested that halothane binding to the four-alpha-helix bundle was improved by (1) introducing a cavity into the hydrophobic core and (2) substituting a methionine side-chain in place of an alpha-helical heptad e position leucine. In this study, the ability of the general anesthetics chloroform and 2,2,2-trichloroethanol to bind to the hydrophobic core of the four-alpha-helix bundle (Aalpha2-L38M)2 is explored. The halogenated alkane chloroform binds with a dissociation constant (Kd) = 1.4 +/- 0.2 mM, whereas 2,2,2-trichloroethanol binds with a Kd = 19.5 +/- 1.2 mM. The affinity of both general anesthetics for the hydrophobic core of the four-alpha-helix bundle approximates their whole animal effective concentration in 50% of test subjects' (EC50) values, as shown previously for halothane. Tryptophan phosphorescence decay rates at 77 K are accelerated by a factor of 4.5 by both bound halothane and chloroform, indicating that the heavy-atom effect is responsible for a portion of the observed fluorescence quenching. Because heavy-atom effects are operative only at short distances, the findings indicate that these general anesthetics are binding in the vicinity of the indole rings of W15 in the hydrophobic core of the four-alpha-helix bundle scaffold. The results indicate that chloroform, halothane and 2,2,2-trichloroethanol may occupy the same sites on protein targets.     

Liquid chromatography and electron-capture dissociation in Fourier transform ion cyclotron resonance mass spectrometry

Liquid separation methods in combination with electrospray mass spectrometry as well as the recently introduced fragmentation method electron capture dissociation (ECD) have become powerful tools in proteomics research. This paper presents the results of the first successful attempts to combine liquid chromatography (LC) and Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) with ECD in the analysis of a mixture of standard peptides and of a bovine serum albumin tryptic digest. A novel electron injection system provided conditions for ECD sufficient to yield extensive sequence information for the most abundant peptides in the mixtures on the time-scale of the chromatographic separation. The results suggest that LC/ECD-FTICRMS can be employed in the characterization of peptides in enzymatic digests of proteins or protein mixtures and identify and localize posttranslational modifications.     

Theoretical study of the human DNA repair protein HOGG1 activity

We have examined the role of the catalytic lysine (Lys 249) in breaking the glycosidic bond of 8-oxoguanine in the enzyme human 8-oxoguanine DNA glycosylase. Until quite recently it has been assumed that this lysine acts as a nucleophile in an S(N)2 type of reaction after being activated through a donation of a proton to a strictly conserved aspartate, also located in the active site. However, evidence from crystallographic, as well as biochemical studies, questions this assumption mainly because the lysine is not ideally positioned for such an attack. In addition, the catalytic activity is preserved even after that aspartate is mutated to a residue not accepting protons, but still keeping the interactions in the active site. In this study, we have investigated several different reaction mechanisms to discover plausible ways where the lysine could assist in breaking the glycosidic bond. We use hybrid density functional theory to characterize both associative and dissociative pathways. We find that the smallest energetical barrier involves an S(N)1 type of mechanism where the lysine electrostatically stabilizes the dissociating base and then donates a proton with a very small barrier and then finally attacks the sugar ring to create the covalently bound protein-DNA intermediate complex. The S(N)2 mechanism also has a lower barrier than the "spontaneous" bond breaking but considerably above that of the S(N)1 reaction. However, in current conditions, the reactants placed in a conformation posed for an S(N)2 reaction is substantially more stable than if posed for the S(N)1 reaction, indicating that the active site has to bind stronger to the latter in order to achieve a full catalytic effect. An analysis of the polarization of the transition states shows that the polarization is largest for the S(N)1 reaction, indicating that this path will gain most by being placed in a prepolarized active site. These findings give further support to the hypothesis that a dissociative mechanism may be the preferred mode of action for this type of enzymes.     

Adsorption of n-butyl-substituted tetrathiafulvalene dodecanethiol on gold

Tetrathiafulvalene (TTF) derivative substituted with two butyl- and two dodecylthiol chains is adsorbed on polycrystalline gold. The TTF-derived thiol adsorbates were characterized by ellipsometry, contact angle goniometry, infrared and X-ray photoelectron spectroscopy and cyclic voltammetry. The molecule is strongly anchored on the gold surface through the sulfur terminating the alkylthiol chains. On the average, the TTF moiety is oriented extended away from the gold surface. The topmost layer of the film containing the dibutyl chains is disordered with gauche defects. The molecule was organized with majority of the alkylthiol chains bound to the gold surface. There are indications of pinholes in the monolayer due to steric hindrance of the bulky TTF rings. The molecular systems consisting of an electroactive pi-system such as TTF, are promising for thin-film field effect transistor application.     

Eine nicht erwartete umlagerungsreaktion von verzweigten triketonen

Heating 2-acyl-alkane-1,4-diones $\text{1}$ to temperatures above 120°C causes an acylgroupmigration leading to 3-acyl-alkane-1,4-diones.     

High pressure raman study of isotropic lineshapes of aqueous sodium nitrate solutions

The isotropic lineshape of the v₁ (A₁) stretching mode of the nitrate ion in solutions of sodium nitrate has been studied at 25°C as a function of NaNO₃ concentration ranging from 0.1 to 6M. The pressure dependence has been determined for 1 and 6M solutions at pressures ranging from 1 bar to 3 kbar. The isotropic band becomes more asymmetric with increasing concentration, and its v₁ peak frequency undergoes a blue shift both with increased concentration and increased pressure. At low concentration the vibrational correlation function is well described by the Kubo formula, whereas at higher concentration it becomes more Gaussian. The experimental data indicate that the v₁ vibrational lineshape in aqueous solutions of NaNO₃ is dominated by strong intermolecular interactions which produce inhomogeneous broadening at higher concentration.     

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-dioxolan-2-yl]nucleosides as Potential Inhibitors of HIV

The synthesis of 1,3-dioxolan-2-ylnucleosides and related chemistry is described. We have shown that 2-methoxy-1,3-dioxolane (6) reacts with silylated thymine and trimethylsilyl triflate to give the acyclic formate ester 1-[2-(formyloxy)ethyl]thymine (8) rather than 1-(1,3-dioxolan-2-yl)thymine (7). A tentative mechanism which could explain this result is discussed. On the other hand, 2-methoxy-1,3-dioxolane 13c reacts with silylated bases to give [4,5-bis(hydroxymethyl)-1,3-dioxolan-2-yl]nucleosides, thus representing the first examples of this novel class of compounds. The nature of the nucleobase and the hydroxyl protecting groups was found to have great influence on the reaction and on the stability of the nucleosides. Compounds 16 and 18 were found to be inactive when tested for anti HIV-1 activity in vitro.