A comparison of electron ionization mass spectra obtained at 70 eV,low electron energies,and with cold EI and their NIST library identification probabilities

Electron ionization (EI) mass spectra of 46 compounds from several different compound classes were measured. Their molecular ion abundances were compared as obtained with 70‐eV EI, with low eV EI (such as 14 eV), and with EI mass spectra of vibrationally cold molecules in supersonic molecular beams (Cold EI). We further compared these mass spectra in their National Institute of Standards and Technology (NIST) library identification probabilities. We found that

1. Low eV EI is not a soft ionization method, and it has little or no influence on the molecular ion relative abundances for large molecules and those with weak or no molecular ions.
2. Low eV EI for compounds with abundant or dominant molecular ions in their 70 eV mass spectra results in the reduction of low mass fragment ions abundances thereby reducing their NIST library identification probabilities thus rarely justifies its use in real‐world applications.
3. Cold EI significantly enhances the relative abundance of the molecular ions particularly for large compounds; yet, it retains the low mass fragment ions; hence, Cold EI mass spectra can be effectively identified by the NIST library.
4. Different standard EI ion sources provide different 70 eV EI mass spectra. Among the Agilent technologies ion sources, the “Extractor” exhibits relatively abundant molecular ions compared with the “Inert” ion source, while the “High efficiency source” (HES) provides mass spectra with depleted molecular ions compared with the “Inert” ion source or NIST library mass spectra.

These conclusions are demonstrated and supported by experimental data in nine figures and two tables.     

A hybrid polymer gel and its static nonergodicity

We used a thermally reversible hybrid gel made of billions of physically jam-packed, swollen, thermally sensitive poly(N-isopropyl-acrylamide) chemical microgels. Laser light scattering study on a series of such hybrid gels formed at different gelling rates and temperatures revealed that the position-dependence of the scattering speckle pattern (static nonergodicity) came from large voids formed during the sol-gel transition. With proper preparation, such nonergodicity is completely removed, indicating that the static nonergodicity generally observed in a gel is not intrinsic, but comes from clustering “island” structures formed during the gelation process.     

One Step Synthesis of α-Substituted α, β-Unsaturated Aldehydes

Abstract

The conversion of carbonyl compounds into cmologated α, β-unsaturated aldehydes (“formylolefination”) is a highly useful transformation in organic synthesis. A large number of methods have been reported for effecting such a chain lengthening. These proceed mainly via silylated intermediates or via phosphorylated reagents. The “phosphonate-strategy” has found widespread use, but leads exclusively to α,β-unsaturated aldehyess, non-substituted in the α-position.     

From “Living” Carbocationic to “Living” Radical Polymerization

Abstract

“Living” carbocationic polymerization is compared to the “living” radical process. Similarities and differences are discussed. “Living” radical polymerization of vinyl acetate and methyl methacrylate to provide polymers with controlled molecular weights and narrow molecular weight distribution (M_w/M_n < 1.2) are presented.     

Comparative molecular surface analysis (CoMSA) for virtual combinatorial library screening of styrylquinoline HIV-1 blocking agents

We used comparative molecular surface analysis to design molecules for the synthesis as part of the search for new HIV-1 integrase inhibitors. We analyzed the virtual combinatorial library (VCL) constituted from various moieties of styrylquinoline and styrylquinazoline inhibitors. Since imines can be applied in a strategy of dynamic combinatorial chemistry (DCC), we also tested similar compounds in which the -C=N- or -N=C- linker connected the heteroaromatic and aromatic moieties. We then used principal component analysis (PCA) or self-organizing maps (SOM), namely, the Kohonen neural networks to obtain a clustering plot analyzing the diversity of the VCL formed. Previously synthesized compounds of known activity, used as molecular probes, were projected onto this plot, which provided a set of promising virtual drugs. Moreover, we further modified the above mentioned VCL to include the single bond linker -C-N- or -N-C-. This allowed increasing compound stability but expanded also the diversity between the available molecular probes and virtual targets. The application of the CoMSA with SOM indicated important differences between such compounds and active molecular probes. We synthesized such compounds to verify the computational predictions.     

Analyse des composes fluores corrosifs par chromatographie gazeuse : Controle du fluor libre

A purely chromatographie and sufficiently general method is described for the analysis of molecular fluorine in permanent inert gases or in other corrosive fluorine compounds (UF₆, HF). The method is also applied to the analysis of permanent inert gases (even in trace quantities) in the same fluorine compounds. In this method, one or several chemical “precolumns” are placed in series with a gas-liquid chromatography column. The “precolumn” system retains or destroys the corrosive compounds (UF₆, HF, F₂) and the chromatography column separates the components formed.     

ON THE PHOSPHORUS-31 CHEMICAL SHIFTS OF SUBSTITUTED TRIARYLPHOSPHINES

Abstract

The ³¹P chemical shifts of eleven (4-ZC₆H₄)₃P compounds show a slight correlation with the Hammet [sgrave]para constant of Z. The unusually large upfield chemical shifts of (2-ZC₆H₄)₃P compounds are attributed to an extreme “gamma” effect caused by the restricted conformations due to the steric influence of the ortho substituents. Chemical shifts are given for about thirty triarylphosphines, and group contributions to phosphine chemical shifts are listed for twenty-one aryl groups.     

On the Availability of 2,3,4,6-Tetra-O-Acetyl-B-D-Glucopyranosyl Isothiocyanate,a Chiral Derivatizing Agent in HPLC

Abstract

During the last few years, the chiral derivatizing agent 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosy isothiocyanate (TAGIT) has been shown to be valuable in the separation of the enantiomers of a variety of compounds by HPLC, The sale of the reagent by its sole commercial supplier was recently discontinued, but its unacetylated analog was made available. The chemical structure of a sample of the unacetylated compound obtained from the supplier was investigated using methane and ammonia chemical ionization mass spectrometry, proton nuclear magnetic resonance, comparison of melting points, and HPLC. By all these criteria the “unacetylated” compound was shown to be, in fact, the acetylated analog, i.e., TAGIT. In view of the value of TAGIT in HPLC, its continued availability, confirmed by the supplier, is welcome.     

Kowist: a computer-assisted systematic approach to finding new compound classes of pesticides

A large collection of chemical compounds and their test data in plant protection was evaluated and explored for hidden classes of pesticides which has not been noticed because by chance no strinkingly active representative had been tested. Special methods were developed in order to correlate, with reasonable computer effort, a maximum (10⁵) of compound classes with the activities of their members. A dialog system was created for the evaluation of the results by the bench chemist. This system is also useful for surveying well-known pesticide classes in order to discover promising gaps in their “chemical spaces”, i.e., new leads.     

The First Chromatographic Resolution of a Chiral Phosphane. An Efficient Synthesis of (R,R)- and (S,S)-DIPAMP

Abstract

Resolution of racemic compounds by chromatography on chiral stationary phases (CSPs) offers several advantages compared with “classical” resolution: no waste of either antipode, no dependence on the e.e. of the chiral auxiliary (CSP), no necessity for chemical transformation. The mean loadability of most CSPs can be compensated if a racemic catalyst is resolved: the chromatographically produced “chiral information” will subsequently be multiplied.     

Hybrid molecular nanostructures with donor-acceptor chains

We have fabricated hybrid molecular chain structures formed by electron acceptor compound 1 and electron donor molecules 2 and 3 at the liquid/solid interface of graphite surface.The structural details of the mono-component and the binary assemblies are revealed by high resolution scanning tunneling microscopy (STM).Compound 1 can form two well-ordered lamellar patterns at different concentrations.In the co-adsorption structures,compounds 2 and 3 can insert into the space between molecular chains of compound 1 and form large area well-ordered nanoscale phase separated lamellar structures.The unit cell parameters for the coassemblies can be "flexibly" adjusted to make the electron donors and acceptors perfectly match along the molecular chains.Scanning tunneling spectroscopy (STS) results indicate that the electronic properties of individual molecular donors and acceptors are preserved in the binary self-assembly.These results provide molecular insight into the nanoscale phase separation of organic electron acceptors and donors on surfaces and are helpful for the fabrication of surface supramolecular structures and molecular devices.     

Structure-Property Relationships in a Polymer

The way in which polymer molecular structure controls structure on higher levels of organization in a solid polymer is briefly reviewed, as is also the way in which structure, on all levels, controls physical properties. The “line of descent” from molecular structure to physical properties is then illustrated for cis-polyisoprene (natural rubber). It is shown how the crystalline-amorphous morphology in the solid is controlled both by the chemical microstructure of the polymer and by the physical conditions (temperature, time, strain) under which solidification occurs. By changing these “processing conditions” great changes can be effected in the morphology.     

Late-Stage C(sp2)−H Functionalization: A Powerful Toolkit To Arm Natural Products for In Situ Proteome Profiling?

The comprehensive investigation of target interactions from native cellular environments is of paramount importance for natural products and related bioactive compounds in drug discovery and chemical biology. Current chemoproteomic tools, such as in situ proteome profiling can do so effectively, but rely heavily on “tagged” probes that are accessible through traditional organic synthesis at the reactive sites of a compound, which may often be required for target binding. Late-stage functionalization may resolve such limitations by tagging compounds in a single step at biologically inert C−H bonds. Herein, recent advances in late-stage C(sp²)−H functionalization of (hetero)arenes, which are present in many natural products, are summarized, and new toolkits for more widespread use of such strategies to install natural products with next-generation “minimalist” linkers for in situ proteome profiling are suggested.     

The Pyrolysis of Azides in the Gas Phase

The chemistry of the non-metallic elements has in recent years passed through a period of rapid development, often referred to as its “renaissance”. To emphasize just one of the key facets: numerous short-lived molecules containing multiple bonds to elements of the third and higher periods have been discovered, often accompanied by the planned synthesis of derivatives which are sterically shielded by bulky groups and thus kinetically stabilized. Thus today molecules such as silabenzenes H₆C_6?nSi_n and silaethenes H₂Si?CH₂ or R₂Si?CR₂, disilenes R₂Si?SiR₂ and diphosphenes RP?PR, silaphenylisonitrile H₅C₆? N?Si, or methylidyne-phosphanes R? C?P, are all well-known species. Sandwich compounds with P₆ rings or silicon centers demonstrate that there are now hardly any barriers to impede the imagination of the non-metal chemist. In sharp contrast is our lack of knowledge regarding the “microscopic” pathways of chemical reactions: thus apart from information provided for example by molecular beam experiments, or from exact numerical calculations involving species consisting of only a few atoms, it remains largely unknown from which directions medium-sized molecules must approach each other to successfully collide and form a “reaction complex”, in which way their structures are changed in such a process or which role is played by molecular dynamics in the energy transfer.–The pyrolysis of azides X? N₃, i.e. compounds which tend to explode violently when ignited in the condensed phase but can be heated in low-pressure gas flow systems without much risk, illustrates that studies of reactive intermediates are of interest not only because novel molecules may be discovered and isolated, and thereby possibilities for synthesis expanded. Moreover, some aspects of the “microscopic” pathways of these azide pyrolyses can be described satisfactorily on the basis of calculated energy hypersurfaces, and the influence of molecular dynamics becomes experimentally visible in the “chemical activation” of intermediates which leads to their “thermal explosion”.     

A Rapid Method for the Prefractionation of Essential Oils. Application to the Essential oil of Black Spruce [Picea Mariana (Mill.) BSP.]

Abstract

A rapid method for the prefractionation of complex essential oils, prior to the identification of their components, is described. The use of “hybrid” flash chromatography, developed in our laboratories, in a specially constructed, jacketed column, which permits the use of low boiling solvents, makes it possible to effect satisfactory separations through a single column rather than through multiple columns as in classical methods, and in a fraction of the time required. The procedure enables a facile separation of hydrocarbons from oxygenated compounds and yields, in some instances, fractions of pure compounds. Enriched fractions of trace constituents are also obtainable for identification by gas chromatography. The method is rapid and inexpensive.     

Improving (Q)SAR predictions by examining bias in the selection of compounds for experimental testing

ABSTRACT

Existing data on structures and biological activities are limited and distributed unevenly across distinct molecular targets and chemical compounds. The question arises if these data represent an unbiased sample of the general population of chemical-biological interactions. To answer this question, we analyzed ChEMBL data for 87,583 molecules tested against 919 protein targets using supervised and unsupervised approaches. Hierarchical clustering of the Murcko frameworks generated using Chemistry Development Toolkit showed that the available data form a big diffuse cloud without apparent structure. In contrast hereto, PASS-based classifiers allowed prediction whether the compound had been tested against the particular molecular target, despite whether it was active or not. Thus, one may conclude that the selection of chemical compounds for testing against specific targets is biased, probably due to the influence of prior knowledge. We assessed the possibility to improve (Q)SAR predictions using this fact: PASS prediction of the interaction with the particular target for compounds predicted as tested against the target has significantly higher accuracy than for those predicted as untested (average ROC AUC are about 0.87 and 0.75, respectively). Thus, considering the existing bias in the data of the training set may increase the performance of virtual screening.     

Ionic Distribution Coefficients and Electrochemical Potentials

Abstract

A novel “electrochemical ionic distribution coefficient”, i is defined based on Guggenheim's electrochemical potential concept. i correlates the activities of a given ion in different solvents. The definition of i is entirely consistent with the practice to interrelate chemical equilibrium constants in various solvents via the classical ionic distribution coefficient i.