DFT characterization of nanostructured germanium surfaces induced by cobalt atoms

By deposition in ultra‐high vacuum of cobalt on a Ge(111)–c(2 × 8) surface, Mocking et al. obtained a surface reconstruction. In the present paper, we analyse the related atomic structure, proposed by these authors, by means of density functional theory calculations. The surface presents ordered clusters that consist of six Ge atoms arranged in a triangle, lying above three Co atoms. The latter are located at substitutional positions within the top plane of the Ge(111) first bilayer. These clusters are similar to what is obtained on part of the Co‐induced Si(111) surface. For this surface, the clusters are terminated either by six Si atoms or by one, two or three adatoms above the six Si atoms. As the Co–Ge clusters systematically display six protrusions in the scanning tunnelling microscopy measurements by Mocking et al., we investigated why Ge adatoms are not present. Comparison of the Gibbs energy, interatomic distances, as well as charge density indicates that Ge adatoms on top of Co‐Ge clusters are less stable than Si adatoms in the Co‐Si system. Copyright © 2013 John Wiley & Sons, Ltd.     

Structural and Functional Analysis of Bacterial Sulfonosphingolipids and Rosette-Inducing Factor 2 (RIF-2) by Mass Spectrometry-Guided Isolation and Total Synthesis

We have analyzed the abundance of bacterial sulfonosphingolipids, including rosette-inducing factors (RIFs), in seven bacterial prey strains by using high-resolution tandem mass spectrometry (HRMS²) and molecular networking (MN) within the Global Natural Product Social Molecular Networking (GNPS) web platform. Six sulfonosphingolipids resembling RIFs were isolated and their structures were elucidated based on comparative MS and NMR studies. Here, we also report the first total synthesis of two RIF-2 diastereomers and one congener in 15 and eight synthetic steps, respectively. For the total synthesis of RIF-2 congeners, we employed a decarboxylative cross-coupling reaction to synthesize the necessary branched α-hydroxy fatty acids, and the Garner-aldehyde approach to generate the capnine base carrying three stereogenic centers. Bioactivity studies in the choanoflagellate Salpingoeca rosetta revealed that the rosette inducing activity of RIFs is inhibited dose dependently by the co-occurring sulfonosphingolipid sulfobacins D and F and that activity of RIFs is specific for isolates obtained from Algoriphagus.     

Base-specific Photocleavage of DNA Induced by Pazelliptine Sensitization: Study of the Mechanism by Time-resolved Absorption and Fluorescence

The intercalating antitumoral drug pazelliptine (PZE) is able to photosensitize the formation of single- and double-strand breaks in supercoiled plasmid DNA and selective photocleavage at guanine residues is observed. In order to understand the mechanisms of DNA cleavage mediated by the photoexcited drug, singlet and triplet excited-state processes in PZE complexed with poly(dA-dT)-poly(dA-dT), poly(dG-dC)-poly(dG-dC) and calf thymus DNA have been investigated by means of single photon counting fluorescence decay and transient absorption techniques. For each complex, three different binding sites have been identified, due to the existence of different geometric structures of the drug in the ground state. For one type of binding site, a proton transfer reaction occurs in the singlet excited state whatever the nucleic acid environment. In contrast, the relaxation dynamics for the other two sites are found to depend widely upon the type of polynucleotide in which the drug has been intercalated. From the results of this study, we suggest that the photodynamic action of PZE does not originate from excitation of the drug in the environment of G-C base pairs but is initiated from its triplet state that reacts by electron transfer with the adenine bases. The specificity of cleavage could be the result of subsequent reactions leading to guanine oxidation.     

Analysis of aflatoxin B1-lysine adduct in serum using isotope-dilution liquid chromatography/tandem mass spectrometry

A method for quantitative analysis of aflatoxin B1-lysine adduct (B1-Lys) in serum by liquid chromatography using tandem mass spectrometry (LC/MS/MS) is presented. The protein in a 250-microL sample was digested in the presence of a stable-isotope internal standard during a 4-h incubation at 37 degrees C with Pronasetrade mark. B1-Lys and the internal standard were extracted using mixed-mode solid-phase extraction cartridges and eluted with 2% formic acid in methanol. Following evaporation and reconstitution, extracts were injected onto a Luna C-18(2) column and eluted with a step gradient of acetonitrile and 0.06% formic acid. The B1-Lys and the internal standard were detected in a positive ionization selective reaction monitoring mode with a ThermoFinnigan TSQ Quantum triple quadrupole mass spectrometer. Calibration curves were linear for concentrations from 0.05-8.0 ng/mL. The method was validated with aflatoxin B1 dosed rat serum diluted to anticipated high and low concentrations. Total imprecision determined from 30 measurements over 15 days was 5.6% and 9.1%, respectively. Recoveries of 78.8 +/- 6.4% for B1-Lys and 85.4 +/- 12.4% for the internal standard were based on the full extraction and reconstitution processes. The method can be used to quantitate B1-Lys at the 0.5 pg/mg albumin level and is suitable for routine analysis.     

The GROMOS software for biomolecular simulation: GROMOS05

We present the latest version of the Groningen Molecular Simulation program package, GROMOS05. It has been developed for the dynamical modelling of (bio)molecules using the methods of molecular dynamics, stochastic dynamics, and energy minimization. An overview of GROMOS05 is given, highlighting features not present in the last major release, GROMOS96. The organization of the program package is outlined and the included analysis package GROMOS++ is described. Finally, some applications illustrating the various available functionalities are presented.     

A proteome-wide CDK/CRK-specific kinase inhibitor promotes tumor cell death in the absence of cell cycle progression

The identification of molecular determinants of tumor cell survival is an important objective in cancer research. Here, we describe a small-molecule kinase inhibitor (RGB-286147), which, besides inhibiting tumor cell cycle progression, exhibits potent cytotoxic activity toward noncycling tumor cells, but not nontransformed quiescent fibroblasts. Extensive yeast three-hybrid (Y3H)-based proteome/kinome scanning with chemical dimerizers revealed CDK1/2/3/5/7/9 and the less well-characterized CDK-related kinases (CRKs) p42/CCRK, PCTK1/3, and PFTK1 as its predominant targets. Thus, RGB-286147 is a proteome-wide CDK/CRK-specific kinase inhibitor whose further study could yield new insight into molecular determinants of tumor cell survival. Our results also suggest that the [1, 3, 6]-tri-substituted-pyrazolo[3,4-d]-pyrimidine-4-one kinase inhibitor scaffold is a promising template for the rational design of kinase inhibitors with potential applications to disease indications other than cancer, such as neurodegeneration, cardiac hypertrophic growth, and AIDS.     

Template-aluminosilicate structures at the early stages of zeolite ZSM-5 formation. A combined preparative, solid-state NMR, and computational study

Species at three stages in the self-assembly of zeolite ZSM-5 have been studied with one- and two-dimensional magic-angle-spinning 13C, 27Al, 29Si, and 1H NMR spectroscopy and compared with the earlier proposed structures: (1) precursor species containing 33-36 T sites around a tetrapropylammonium (TPA) cation, (2) nanoslabs consisting of a flat 4 x 3 array of such precursors, and (3) the final TPA-ZSM-5 zeolite. Synthesis was carried out in D2O to suppress the water and silanol protons. Under such conditions, the effective Si-H and Al-H distances measured with 29Si-{1H} and 27Al-{1H} rotational echo double resonance (REDOR) reflect the interactions between TPA cations and the surrounding aluminosilica. The 29Si-{1H} REDOR curves for Q4-type silicon atoms at the three mentioned stages are closely similar, as well as the observed 27Al-1H REDOR curve for the precursor species compared to that for the TPA-ZSM-5. This indicates that in addition to externally attached TPA, there is also internal TPA already incorporated at an early stage into the aluminosilicate in a similar way as in the final zeolite, in accordance with the earlier proposed MFI self-assembly pathway (Kirschhock et al. Angew. Chem. Int. Ed. 2001, 40, 2637). However, the effective distances extracted from the initial REDOR curvatures are significantly (10-15%) larger than those computed for the model. Since there is no temperature effect, we tentatively assign this difference to a reduction of the 29Si-1H and 27Al-1H interactions by multispin decoherence effects or self-decoupling caused by proton spin diffusion. By assuming the computed model distances and fitting Anderson-Weiss curves to the observed REDOR data, we obtain similar "decoherence times" in the order of 0.1 ms. The observed 29Si-{1H} REDOR dephasing for the Q3 sites in the precursors is significantly faster than that for the Q4 sites. This is tentatively ascribed to a partial deuteron-proton back exchange at the silanol positions.     

Development of electrochemical processes for nitrene generation and transfer

An electrochemical strategy for running nitrogen-transfer reactions on chemically inert anode surfaces has been developed. The generation and trapping of highly reactive nitrene-transfer reagents can be accomplished under mild conditions on platinum electrodes. The key factor that accounts for the high levels of chemoselectivity in this process is the phenomenon of overpotential. We have found that molecules that are similar in terms of propensity toward oxidation can be differentiated on the basis of their affinity to a given electrode surface. Thereby, reactive species can be selectively generated in the presence of acceptor molecules of interest. Specifically, a wide range of structurally dissimilar olefins can be transformed into the corresponding aziridines in the presence of N-aminophthalimide. Likewise, nitrene generation in the presence of sulfoxides leads to their chemoselective transformation into the corresponding sulfoximines. In this paper we discuss the underlying mechanistic foundation of these reactions.     

pentafluorophenyl-phenyl interactions in biphenyl-DNA

We prepared and investigated oligonucleotide duplexes of the sequence d(GATGAC(X)nGCTAG).d(CTAGC(Y)nGTCATC), in which X and Y designate biphenyl- (bph) and pentafluorobiphenyl- ((5F)bph) C-nucleotides, respectively, and n varies from 0-4. These hydrophobic base substitutes are expected to adopt a zipperlike, interstrand stacking motif, in which not only bph/bph or (5F)bph/(5F)bph homo pairs, but also (5F)bph/bph mixed pairs can be formed. By performing UV-melting curve analysis we found that incorporation of a single (5F)bph/(5F)bph pair leads to a duplex that is essentially as stable as the unmodified duplex (n=0), and 2.4 K more stable than the duplex with the nonfluorinated bph/bph pair. The T(m) of the mixed bph/(5F)bph pair was in between the T(m) values of the respective homo pairs. Additional, unnatural aromatic pairs increased the T(m) by +3.0-4.4 K/couple, irrespective of the nature of the aromatic residue. A thermodynamic analysis using isothermal titration calorimetry (ITC) of a series of duplexes with n=3 revealed lower (less negative) duplex formation enthalpies (DeltaH) in the (5F)bph/(5F)bph case than in the bph/bph case, and confirmed the higher thermodynamic stability (DeltaG) of the fluorinated duplex, suggesting it to be of entropic origin. Our data are compatible with a model in which the stacking of (5F)bph versus bph is dominated by dehydration of the aromatic units upon duplex formation. They do not support a model in which van der Waals dispersive forces (induced dipoles) or electrostatic (quadrupole) interactions play a dominant role.     

Aromaticity and electron affinity of Carbo(k)-[3]radialenes, k=0, 1, 2

Aromaticity enhancement is a possible driving force for the low reduction potentials of buta-1,3-diynediyl-expanded [N]radialenes: this hypothesis is theoretically analyzed for the expanded [3]radialene prototype. This study is undertaken within a more general prospect, namely the evaluation of the variation of aromaticity with endocyclic and peripheral carbomeric expansion of [3]radialene and its mono- and dianions. The structures, denoted as [C-H](6) (h)[C-C](3) (k)carbo-[3]radialene(q) (h=0, 1; k=0, 1, 2; q=0, -1, -2), were optimized in relevant singlet, doublet, or triplet spin states at the B3PW91/6-31G** level. They were found to be all planar. The structural aromaticity was measured through the average bond length d(av) over the [C-C](3) (k)carbo-[3]radialene core, and by the corresponding bond-length equalization parameter sigma(d), related to Krygowski's GEO. The magnetic aromaticity was measured by Schleyer's NICS values at the center of the rings. Regarding the relative variation of NICS and sigma(d), two classes of species can be distinguished according to their endocyclic expansion level. The species with a nonexpanded (k=0) or doubly expanded (k=2) ring constitute the first class: they exhibit D(3h) symmetry and a strong correlation of NICS with sigma(d). The species with a singly expanded ring (k=1) fall far from the correlation line, and constitute the second class. This class distinction is related to the degeneracy scheme of the frontier orbitals of the neutral representative. A finer appraisal of the electron (de)localization is brought by the ELF (Electron Localization Function) analysis of the electron density. It allows for a weighting of relevant resonance forms. Unsubstituted species are well described by the superimposition of two or three resonance forms. For (doublet spin state) monoanionic species, their respective weights are validated by comparison with AIM spin density. The weighted mean, n, of the formal numbers of paired pi(z) electrons in the resonance forms was calculated and compared with the closest even integer of either forms 4m+2 or 4m. A density-based continuous generalization of the orbital-based discrete Hückel rule is then heuristically proposed through an analytical correlation of NICS versus sigma(d), n, and S, the spin of the species. The frontier-orbital-degeneracy pattern of neutral species is discussed with respect to structural and magnetic aromaticity criteria. A decreasing HOMO-LUMO gap versus endocyclic expansion is obtained, but [C-C](3) (1)carbo-[3]radialene possesses the highest HOMO and LUMO energies. Vertical and adiabatic electron affinities of neutral and monoanionic species were also computed and compared with related experimental data.