Conformations of antipyrines

Reliable conformational energetics is essential in interpreting and predicting structures of molecular crystals. We provide a combined density functional theory (DFT)-structural database study, demonstrating that this combination can be used as a foundation for this purpose. A subtle problem of nitrogen pyramidalization is used as the example in antipyrines, a group of bioactive molecules. Nitrogen pyramidalization on the two adjacent sp(3) nitrogens directly affects the orientation of the methyl and phenyl substituents, which tend toward opposite sides of the heteroaromatic ring, affecting crystal packing. Accordingly, the overwhelming majority of the structures of antipyrines in the Cambridge Structural Database (CSD) are either nearly planar or have substituents on the opposite sides of the ring. Recent powder X-ray structures by Lemmerer et al. identified propyphenazone, an antipyrine, to have two substituents on the same side in an apparently sterically crowded conformation. We show that the new structure, although counterintuitive, is not an outlier on the conformational map. A distribution of the conformations of all antipyrines listed in the CSD is in good agreement with the computed conformational map. We also examine the role of the hysteretic property of the phenyl torsion in propyphenazone and its indirect effects on its overall conformation.     

Bonds or not bonds? Pancake bonding in 1,2,3,5-dithiadiazolyl and 1,2,3,5-diselenadiazolyl radical dimers and their derivatives

Unusually long bonds or short intermolecular contacts occur in the title compounds reminiscent of pancake bonding. Pancake bonding interactions seem analogous to π-stacking interactions, but they display much shorter contact distances than normally seen in van der Waals (vdW) dimers. The interpretation of these SN and SeN containing structures has been an outstanding challenge for some time. The antibonding (π*) singly occupied molecular orbital (SOMO) of the radical is the source of two-electron multicenter bonding (2e/mc). Preferred conformations thus can be traced back to SOMO-SOMO overlap. We used several computational methods to understand the nature of pancake bonding in the title compounds including four wave function methods (WFT) and a dozen density functional theories (DFT) including empirical dispersion corrections. We used experimental data and high level CCSD(T)/6-311++G(d,p) and MRPT2/6-311++G(d,p) calculations for comparison. The analysis provided the interpretation a wealth of experimental data including conformational preferences of these SN and SeN containing radical dimers leading to a better overall understanding of pancake bonding. Analysis of the various components of the inter-radical interactions showed that SOMO-SOMO bonding interaction and dispersion interaction contribute to the binding energy and neither of these interactions alone is sufficient to bind the dimer. The dimer is predicted to show weak diradical character.     

ipso-Bromination/iodination of arylboronic acids: Poly(4-vinylpyridine)-Br2/I2 complexes as safe and efficient reagents

Poly(4-vinyl pyridine) supported bromine/iodine complexes were prepared and probed for ipso-bromination/iodination of arylboronic acids. These solid complexes with catalytic amount of additive are found to be safe and efficient reagent system for the ipso-bromination/iodination. The reaction occurs under mild conditions and tolerates various functional groups resulting in products with high selectivity and yields.     

Probing the color structure of the perfect QCD fluids via soft-hard-event-by-event azimuthal correlations

We develop a comprehensive dynamical framework, CIBJET, to calculate on an event-by-event basis the dependence of correlations between soft(p_T2 GeV) and hard(p_T10 GeV) azimuthal flow angle harmonics on the color composition of near-perfect QCD fluids produced in high energy nuclear collisions at RHIC and LHC. CIBJET combines consistently predictions of event-by-event VISHNU2+1 viscous hydrodynamic fluid fields with CUJET3.1 predictions of event-by-event jet quenching. We find that recent correlation data favor a temperature dependent color composition including bleached chromo-electric q(T) + g(T) components and an emergent chromo-magnetic degrees of freedom m(T) consistent with non-perturbative lattice QCD information in the confinement/deconfinement temperature range.     

Property distributions: differences between drugs,natural products,and molecules from combinatorial chemistry

The differences between three different compound classes, natural products, molecules from combinatorial synthesis, and drug molecules, were investigated. The major structural differences between natural and combinatorial compounds originate mainly from properties introduced to make combinatorial synthesis more efficient. These include the number of chiral centers, the prevalence of aromatic rings, the introduction of complex ring systems, and the degree of the saturation of the molecule as well as the number and ratios of different heteroatoms. As drug molecules derive from both natural and synthetic sources, they cover a joint area in property space of natural and combinatorial compounds. A PCA-based scheme is presented that differentiates the three classes of compounds. It is suggested that by mimicking certain distribution properties of natural compounds, combinatorial products might be made that are substantially more diverse and have greater biological relevance.     

Tuning a High Transmission Ion Guide to Prevent Gas-Phase Proton Exchange During H/D Exchange MS Analysis

Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) for protein structural analysis has been adopted for many purposes, including biopharmaceutical development. One of the benefits of examining amide proton exchange by mass spectrometry is that it can readily resolve different exchange regimes, as evidenced by either binomial or bimodal isotope patterns. By careful analysis of the isotope pattern during exchange, more insight can be obtained on protein behavior in solution. However, one must be sure that any observed bimodal isotope patterns are not artifacts of analysis and are reflective of the true behavior in solution. Sample carryover and certain stationary phases are known as potential sources of bimodal artifacts. Here, we describe an additional undocumented source of deuterium loss resulting in artificial bimodal patterns for certain highly charged peptides. We demonstrate that this phenomenon is predominantly due to gas-phase proton exchange between peptides and bulk solvent within the initial stages of high-transmission conjoined ion guides. Minor adjustments of the ion guide settings, as reported here, eliminate the phenomenon without sacrificing signal intensity. Such gas-phase deuterium loss should be appreciated for all HDX-MS studies using such ion optics, even for routine studies not focused on interpreting bimodal spectra.

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Local homeomorphisms onto nonunicoherent continua

We show that ifY is a nonunicoherent continuum and if 1 n < , then there is a local homeomorphism of degreen from some continuumX ontoY.     

Determination of nuclear graphite impurities by prompt gamma activation analysis to support decommissioning operations

Journal of Radioanalytical and Nuclear Chemistry - Elemental composition of non-irradiated nuclear grade graphite was determined by Prompt Gamma Activation Analysis (PGAA) to quantitively assess...     

Transient and First Passage Time Distributions of First- and Second-order Multi-regime Markov Fluid Queues via ME-fication

We propose a numerical method to obtain the transient and first passage time distributions of first- and second-order Multi-Regime Markov Fluid Queues (MRMFQ). The method relies on the observation that these transient measures can be computed via the stationary analysis of an auxiliary MRMFQ. This auxiliary MRMFQ is constructed from the original one, using sample path arguments, and has a larger cardinality stemming from the need to keep track of time. The conventional method to approximately model the deterministic time horizon is Erlangization. As an alternative, we propose the so-called ME-fication technique, in which a Concentrated Matrix Exponential (CME) distribution replaces the Erlang distribution for approximating deterministic time horizons. ME-fication results in much lower state-space dimensionalities for the auxiliary MRMFQ than would be with Erlangization. Numerical results are presented to validate the effectiveness of ME-fication along with the proposed numerical method.