Photoionization of C(4) molecular beam: ab initio calculations

Large computations are performed on the C(4) (+) cation in order to characterize its stable isomers and its lowest electronic excited states using configuration interaction methods and large basis sets. Several stable isomers are found including a linear C(4) (+)(l-C(4) (+)), a rhombic C(4) (+)(r-C(4) (+)) (or cyclic), and a branched (d-C(4) (+)) structure. Our calculations show a high density of electronic states for all of these isomers favoring their interactions. By combining the present ab initio data and those on neutral C(4), the l-C(4)(X)+hnu-->l-C(4) (+)(X(+))+e(-), d-C(4)(X)+hnu-->d-C(4) (+)(X(+))+e(-), and r-C(4)(X)+hnu-->r-C(4) (+)(X(+))+e(-) vertical photoionization transition energies are computed at 10.87, 10.92, and 10.77 eV, respectively. Photoionizing a C(4) molecular beam results on an onset at 10.4-10.5 eV and then to a linear increase of the signal due to the opening of several ionization channels involving most of the C(4) and C(4) (+) isomers and electronic states.     

New solid support for the synthesis of 3'-oligonucleotide conjugates through glyoxylic oxime bond formation

A novel solid support 1 was synthesized to incorporate glyoxylic aldehyde functionality at the oligonucleotide 3'-terminus. 6-mer and 11-mer oligonucleotide sequences containing 3'-glyoxylic aldehyde functionality were prepared by using this support. These modified oligonucleotides were coupled to reporters containing an aminooxy group to prepare oligonucleotide 3'-conjugates through glyoxylic oxime bond formation. The hydrolytic stability of a glyoxylic oxime linkage was also investigated. [reaction: see text].     

Double cation adduction in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of electron deficient anthraquinone derivatives

Six anthraquinone derivatives were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). Clear (pseudo) molecular ions were observed for all the compounds. Interestingly, for some derivatives, strong ions with double cation adduction were also recorded in the positive mode. It is remarkable that all these ions are singly charged. In this work, possible mechanisms for the double cation adduction were investigated and discussed. It appears that the double cation adduction was due to the electron deficient nature of the derivatives, and formed by taking up two singly charged cations and one electron. Substituents on the anthraquinone ring were found to have a significant effect on the double cation adduction. In contrast, no considerable influence of the acidity of MALDI matrix/solution was observed, even on the double proton adduction. Furthermore, it was demonstrated that double cation adduction might occur in the MALDI gas-phase plume. In addition to the anthraquinones, three more electron deficient compounds of different types, i.e. a perylene bisimide derivative (PB), 3,7-decanoylamino-4,8-dihydrobenzo[1,2-b:4,5-b']dithiophene-4,8-dione (TQ) and 6,6-phenyl C61-butyric acid methyl ester (PCBM), were also analyzed with MALDI TOF MS. The results indicate that the 'abnormal' double cation adduction might be a 'normal' phenomenon in the MALDI TOF MS analysis of many electron deficient compounds.     

Direct mass spectrometric analysis of flavors and fragrances in real applications using DART

DART (Direct Analysis in Real Time) is an innovative technology to analyze complex solid samples at atmospheric pressure and ground potential by simply placing them between a DART ion source and a mass spectrometer. The analytes are ionized by a gun of neutral metastable species. The first examples of the application of DART to the analysis of flavor and fragrance raw materials in real, complex applications are reported here. A remarkably high potential of the technique is demonstrated. DART was applied to semi-quantitative analyses of perfumery raw materials deposited on smelling strips. In optimal cases, limits of detection around 100 pg were achieved. DART also allowed the assessment of the deposition and release of fragrance on surfaces such as fabric and hair. Finally, DART permitted the screening of twelve chewing gum samples for the possible presence of taste-refreshing compounds in less than 30 min.     

Free resources to assist structure-based virtual ligand screening experiments

In today's research environment, a wealth of experimental/theoretical structural data is available and the number of therapeutically relevant macromolecular structures is growing rapidly. This, coupled with the huge number of small non-peptide potential drug candidates easily available (over 7 million compounds), highlight the need of using computer-aided techniques for the efficient identification and optimization of novel hit compounds. Virtual (or in silico) ligand screening based on the three-dimensional structure of macromolecular targets (SB-VLS) is firmly established as an important approach to identify chemical entities that have a high likelihood of binding to a target molecule to elicit desired biological responses. A myriad of free applications and services facilitating the drug discovery process have been posted on the Web. In this review, we cite over 350 URLs that are useful for SB-VLS projects and essentially free for academic groups. We attempt to provide links for in silico ADME/tox prediction tools, compound collections, some ligand-based methods, characterization/simulation of 3D targets and homology modeling tools, druggable pocket predictions, active site comparisons, analysis of macromolecular interfaces, protein docking tools to help identify binding pockets and protein-ligand docking/scoring methods. As such, we aim at providing both, methods pertaining to the field of Structural Bioinformatics (defined here as tools to study macromolecules) and methods pertaining to the field of Chemoinformatics (defined here as tools to make better decisions faster in the arena of drug/lead identification and optimization). We also report several recent success stories using these free computer methods. This review should help readers finding free computer tools useful for their projects. Overall, we are confident that these tools will facilitate rapid and cost-effective identification of new hit compounds. The URLs presented in this review will be updated regularly at www.vls3d.com in the coming months, "Links" section.     

Evaluation and application of argon and helium microstrip plasma for the determination of mercury by the cold vapor technique and optical emission spectrometry

The suitability of a 2.45-GHz atmospheric pressure, low-power microwave microstrip plasma (MSP) operated with Ar and He for the determination of Hg by continuous-flow cold vapor (CV) generation, using SnCl₂/HCl as the reducing agent, and optical emission spectrometry (OES) using a small CCD spectrometer was studied. The areas of stability for a discharge in the Ar and in the He MSP enclosed in a cylindrical channel in a quartz wafer were investigated. The excitation temperatures as measured for discharge gas atoms (Ar I, He I), and the electron number densities at 35–40 W and 15–400 mL min⁻¹ were found to be at the order of 3,200–5,500 K and 0.8 × 10¹⁴–1.6 × 10¹⁴ cm⁻³, respectively. The relative intensity of the Hg I 253.6-nm line and the signal-to-background ratio as a function of the forward power (35–40 W) as well as of the flow rate of the working gas (15–400 mL min⁻¹) were evaluated and discussed. For the selected measurement conditions, the Ar MSP was established to have the lower detection limit for Hg (0.6 ng mL⁻¹) compared with the He MSP. The linearity range is up to 300 ng mL⁻¹ and the precision is on the order of 1–3%. With the optimized CV Ar MSP-OES method a determination of Hg in spiked domestic and natural waters at concentration levels of 20–100 μg L⁻¹ and an accuracy of 1–4% could be performed. In an NIST domestic sludge standard reference material, Hg (3.64 μg g⁻¹) could be determined with a relative standard deviation of 4% and an agreement better than 4%.     

Modular and practical synthesis of 6-substituted pyridin-3-yl C-nucleosides

A novel modular and practical methodology for preparation of 6-substituted pyridin-3-yl C-nucleosides was developed. The Heck reaction of 2-chloro-5-iodopyridine with a 3'-TBDMS-protected glycal gave a 6-chloropyridin-3-yl nucleoside analogue, which was then desilylated, selectively reduced, and reprotected to give the TBDMS-protected 6-chloropyridin-3-yl C-2'-deoxyribonucleoside as a pure beta-anomer in a total yield of 39% over four steps. This key intermediate was then subjected to a series of palladium-catalyzed cross-coupling reactions, aminations, and alkoxylations to give a series of protected 1beta-(6-alkyl-, 6-aryl-, 6-hetaryl, 6-amino-, and 6-tert-butoxypyridin-3-yl)-2'-deoxyribonucleosides. 6-Unsubstituted pyridin-3-yl C-nucleoside was prepared by catalytic hydrogenation of the chloro derivative and 6-oxopyridine C-nucleoside by treatment of the 6-tert-butoxy derivative with TFA. Deprotection of all the silylated nucleosides by Et3N.3HF gave a series of free C-nucleosides (10 examples).     

The (+)‐cis‐ and (+)‐trans‐Olibanic Acids: Key Odorants of Frankincense

Frankincense (olibanum) is one of the oldest aromatic materials used by humans, but the key molecular constituents contributing to its characteristic odor remained unknown. Reported herein is the discovery that (1S,2S)‐(+)‐trans‐ and (1S,2R)‐(+)‐cis‐2‐octylcyclopropyl‐1‐carboxylic acids are highly potent and substantive odorants occurring in ppm amounts in all of the frankincense samples analyzed, even those showing radically different volatile compositions. These cyclopropyl‐derived acids provide the very characteristic old churchlike endnote of the frankincense odor.     

Electron Microscopy Study of Nickel and Nickel Composite Electrocoatings

 It has been proved that the electrolysis parameters strongly influence the structural properties of nickel electrodeposits, mainly the crystalline growth, preferred orientation and surface morphology. To determine the structural characteristics of nickel and composite nickel matrix electrocoatings, prepared under either direct current or pulse current conditions, the electron microscopy techniques have proved very important tools. In particular, investigation of the distribution and percentage of microparticles incorporated in the metallic matrix during preparation of nickel composite electrocoatings demands the use of techniques such as energy dispersion spectroscopy (EDS) or image analysis.