Prediction of the molar volume at the normal boiling point

A group contribution method for the prediction of the molar volume at the normal boiling point has been developed. The method can be used for organic and inorganic compounds. It cannot be used for elements and diatomic molecules. Group contributions are shown for a wide variety of hydrocarbons, organic halogen compounds, organic oxygen compounds, organic nitrogen compounds, organic sulfur compounds, organic boron compounds, organic silicon compounds, miscellaneous organics, and many inorganic compounds.Contrary to the corresponding states methods for the prediction of molar volumes, knowledge of critical properties, acentric factors, and reference volumes is not needed.     

Data shaving: a focused screening approach

The number of compounds available for evaluation as part of the drug discovery process continues to increase. These compounds may exist physically or be stored electronically allowing screening by either actual or virtual means. This growing number of compounds has generated an increasing need for effective strategies to direct screening efforts. Initial efforts toward this goal led to the development of methods to select diverse sets of compounds for screening, methods to cluster actives into related groups of compounds, and tools to select compounds similar to actives of interest for further screening. In this work we extend these earlier efforts to exploit information about inactive compounds to help make rational decisions about which sets of compounds to include as part of a continuing screening campaign, or as part of a focused follow-up effort. This method uses the information from inactive compounds to "shave" off or deprioritize compounds similar to inactives from further consideration. This methodology can be used in two ways: first, to provide a rational means of deciding when sufficient compounds containing certain structural features have been tested and second as a tool to enhance similarity searching around known actives. Similarity searching is improved by deprioritizing compounds predicted to be inactive, due to the presence of structural features associated with inactivity.     

GC FPD method for the simultaneous speciation of butyltin and phenyltin compounds in waters

A method is described for the simultaneous determination of nanogram amounts of mono-, di- and tri-butyltin compounds in water. The procedure is based on the conversion of tin compounds to volatile species by Grignard pentylation and analysis using GC with flame photometric detection (GC FPD). The ionic compounds are extracted from diluted acidified (HBr) aqueous solutions by using a pentane-tropolone solution. The extracted organotin compounds are pentylated by a Grignard reagent and purified on a Fluorisil column before analysis by GC FPD. The detection limits are 20 ng dm^?3 for butyltin compounds and 50 ng dm^?3 for phenyltin compounds. Recoveries from spiking experiments in tap-water and natural seawater matrices, in which no organotin compounds were detected, were greater than 90% for most of the alkyltin compounds.     

Method optimization by solid-phase microextraction in combination with gas chromatography with mass spectrometry for analysis of beer volatile fraction

A simple and sensitive method for the analysis of beer volatile compounds was optimised using headspace solid-phase microextraction (SPME) and gas chromatography with mass detection. Headspace SPME using a 75 microm Carboxen-polydimethylsiloxane (CAR-PDMS) fiber provided effective sample enrichment and enabled extraction of a wide variety of compounds. The reproducibility depended on the compounds, with a mean value of 1.4% for alcohols, 3.3% for ethers, 6.7% for aldehydes, 3.4% for acids, 1.7% for aromatic compounds, 2.4% for esters, 7.4% for hydrocarbons, 1.8% for alicyclic compounds, and 3.4% for heterocyclic compounds. The optimised methodology can be used to compare volatile profile from different types of beers and eventually to study the evolution of a particular beer during aging.     

Synthesis of Some Novel Pyrazole‐Substituted 9‐Anilinoacridine Derivatives and Evaluation for their Antioxidant and Cytotoxic Activities

This article focuses on the synthesis of new series of pyrazole‐substituted 9‐anilinoacridine derivatives 5a – m and 6a – l . The compounds were confirmed by physical and analytical data. The synthesized compounds when screened for in vitro antioxidant activity showed promising activity for many compounds. The selected compounds were screened for cytotoxic activity showed promising inhibition of HEp‐2 cell line for the compounds 6c , 6e , and 6f .     

Agostic bonds in cyclometalation

Cyclometalation reactions proceed very easily with one step reaction between metal compounds and substrates having a heteroatom such as O, S, N, P and As. However, under mild reaction conditions, many agostic compounds which are intermediates in these cyclometalation reactions, can be isolated. The metal compounds used for the formation of these agostic intermediates are both transition metal and main group metal compounds. The substrates are nitrogen-containing compounds, phosphorus-containing compounds, oxygen-containing compounds and sulfur-containing compounds. These agostic intermediates are mainly δ-C-H agostic compounds, some are γ-C-H agostic compounds and very few are ?-C-H-agostic compounds. The agostic intermediates are prepared, usually, under mild reaction conditions in the cyclometalation reaction. These agostic compounds are also prepared from cyclometalation reaction products, e.g., by the protonation, irradiation, and elimination of ligand molecules by vacuum, inert gas current, dehydration with a molecular sieves 4A, etc. Some agostic compounds are utilized for preparation of stable catalysts, e.g., hydrogenation catalysts.     

Comparative study of carbon nanotubes and C(60) fullerenes as pseudostationary phases in electrokinetic chromatography

The use of carbon nanostructures in different modalities is a topic of growing interest. This article provides a systematic comparison of surfactant-coated single-wall carbon nanotubes, multi-wall carbon nanotubes and C(60) fullerenes as pseudostationary phases (PSPs) in electrokinetic chromatography. The differences on the electrophoretic behaviour as a function of the pseudostationary phase for phenolic compounds, triazines and nitroimidazole derivatives have been explored. Phenolic compounds, triazines and nitroimidazole derivatives has been selected as model compounds of aromatic compounds, pi-exceeding heteroaromatic compounds and pi-deficient heteroaromatic compounds, respectively. Resolution was also evaluated on the basis of the differences in the electrophoretic behaviour and in this sense the best PSP for each group of compounds can be proposed.     

Fluorine-containing triphenylenes. Liquid crystalline properties and surface ordering

The synthesis and liquid crystalline properties of two novel series of triphenylenes with 4 or 5 pentafuoropentyloxy tails and 1 or 2 alkoxy tails of varying length are reported. All compounds form wide-range hexagonal columnar phases. The isotropisation temperatures and the corresponding enthalpy changes for the compounds with 4 or 5 fluorinated tails are higher than for the compounds with 6 alkoxy tails, and also higher than for compounds with 6 fluorinated tails. These results indicate that the best ordering is obtained for compounds with a mix of fluorinated and non-fluorinated tails. With increasing length of the alkyl tails in HAT compounds with 4 or 5 fluoroalkoxy tails, the isotropisation temperatures decrease and the d-spacings as observed by XRD increase. All fluoro-containing compounds have a strong tendency for spontaneous homeotropic alignment on surfaces, both hydrophilic and hydrophobic.     

Novel RPLC stationary phases for lipophilicity measurement: solvatochromic analysis of retention mechanisms for neutral and basic compounds

An RPLC was developed to rapidly determine lipophilicity of neutral and basic compounds using three base deactivated RPLC stationary phases particularly designed for the analysis of basic compounds, namely, Supelcosil ABZ(+)Plus, Discovery RP Amide C16, and Zorbax Extend C18. The work consisted of three sets of experiments. In the first log kw values of neutral compounds were extrapolated using hydroorganic mobile phases at different compositions. Good correlation between log kw and log Poct indicated that the method was appropriate for these supports, without adding a silanol masking agent. In the second set of experiments, isocratic log k values of neutral and basic compounds were measured with three different mobile phases. The best estimation of lipophilicity was obtained for neutral and basic compounds when the secondary interactions were strongly reduced (i. e., when basic compounds were under their neutral form). In the third set of experiments, isocratic retention factors of basic compounds (in their neutral form) were measured with a high-pH mobile phase, on a chemically stable support (Zorbax Extend C18). Under these chromatographic conditions, correlation between the isocratic retention factors and log Poct (log D10.5) for basic compounds was similar to that for neutral compounds.     

Doped gelatin films as a model matrix for molecular secondary ion mass spectrometry studies of biological soft tissue

Porcine gelatin films doped with a number of biological compounds at various concentrations and prepared by spin-casting have been used as model biological tissue matrices for studying organic ion emission in molecular secondary ion mass spectrometry. For many compounds, portions of the working curves were found to be linear over several orders of magnitude in concentration. Detection limits for the, analyzed compounds were in the parts per million range for several organic salt compounds but high (0.1 wt%) for others. Owing to the presence of a significant chemical background, the poorest detection limits were generally obtained from compounds with low molecular weights. Secondary ion yield matrix effects, indicated by a reduction in ionization efficiency at higher concentrations, were observed for several organic salt compounds.     

Speciation of organotin compounds by tandem mass spectrometry

The collison-induced dissociation of a range of organotin compounds has been examined by tandem (MS–MS) mass spectrometry in order to investigate the potential of the technique for speciation without prior chromatographic separation. Tables of parent–daughte ion relationships are prepared for a group of six closely related compounds. The results obtained are sufficiently characteristic to distinguish between the isolated compounds and to identify the individual components of a simple mixture. This procedure has potential applications for less volatile compounds and for quantitative analysis.     

Lead validation and SAR development via chemical similarity searching; application to compounds targeting the pY+3 site of the SH2 domain of p56lck

Compound selection based on chemical similarity has been used to validate active "parent" compounds identified via database searching as viable lead compounds and to obtain initial structure-activity relationships for those leads. Twelve parent compounds that have inhibitory activity against the SH2 domain of the p56 T-cell tyrosine kinase (Lck) are the focus of this study. Lck is involved in the T-cell mediated immune response, and inhibitors of Lck protein-protein interactions could potentially be used to develop novel immunosuppressants. Similarity searches for each parent compound were performed using 2D structural fingerprints on a database containing 1,300,000 commercially available compounds. The inhibitory activity of the selected compounds was assessed using enzyme immunoassay (EIA). In general, the most active parent compounds yield the most high activity similar compounds; however, in two cases low activity parent compounds (i.e. inhibitory activity < 25% at 100 microM) yielded multiple similar compounds with activities > 60%. Such compounds may, therefore, be considered as viable lead compounds for optimization. Structure-activity relationships were explored by examining both ligand structures and their computed bound conformations to the protein. Functional groups common to the active compounds as well as key amino acid residues that form hydrogen bonds with the active compounds were identified. This information will act as the basis for the rational optimization of the lead compounds.     

Solid-phase microextraction in the analysis of food taints and off-flavors

Selected food taints and off flavors, for which solid phase microextraction (SPME) has been used as a method for volatiles isolation, are the subject of review. Compounds responsible for musty and earthy odor off-flavors and taints in foods are discussed. This group contains haloanisoles, geosmin, and methylisoborneol. Chlorophenols are discussed as precursors of chloroanisoles and compounds impairing the flavor of food. Also described are volatile phenolic compounds responsible for medicinal off flavors, mainly ethyl phenols and vinyl phenols. Sulfur compounds that contribute to off-flavor are also discussed. Finally, a group of volatile compounds being the products of lipid oxidation are summarized. A short review of the formation, occurrence, and information on odor properties of all of these groups of compounds is given. Examples of SPME use for the analysis of compounds belonging to all described groups are shown. Elaboration of method parameters, fiber selection, experimental conditions, and quantitation of compounds are subjects of interest. Also, applications of SPME as a method for introduction of volatiles in mechanical olfaction technologies are shortly outlined.     

High-throughput prediction of blood-brain partitioning: a thermodynamic approach

A high-throughput in silico screening tool for potentially CNS active compounds was developed on the basis of the correlation of solvation free energies and blood-brain partitioning (log(cbrain/cblood) = log BB) data available from experimental sources. Utilizing a thermodynamic approach, solvation free energies were calculated by the fast and efficient generalized Born/surface area continuum solvation model, which enabled us to evaluate more than 10 compounds/min. Our training set involved a structurally diverse set of 55 compounds and yielded a function of log BB = 0.035Gsolv + 0.2592 (r = 0.85, standard error 0.37). Calculation of solvation free energies for 8700 CNS active compounds (CIPSLINE database) revealed that Gsolv is higher than -50 kJ/mol for the 96% of these compounds which can be used as suitable criteria for the identification of compounds preferable for CNS penetration.     

MDGC–MS: A powerful tool for enantioselective flavor analysis

This paper reports the differentiation between the enantiomers of theaspiranes and theaspirones, potent flavor compounds widely used in the flavor industry. Optically pure reference compounds of isomeric theaspiranes were obtained by enantioselective synthesis. Enantiomerically pure reference theaspirones were isolated from quince fruit; their absolute stereochemistry was assigned by CD spectroscopy. For both types of compounds the order of elution was elucidated by using authentic reference compounds. These data enabled the determination of the enantiomeric distribution of both types of compounds in a variety of plant tissues. Because of the complexity of the natural flavor isolates, compounds were identified by mass spectrometry after multidimensional gas chromatography employing a Sichromat 2 double oven chromatograph. After separation of the target compounds on the first, achiral, column (DB-5), they were transferred to a chiral column (C-Dex B) for determination of the enantiomeric distribution. Multiple ion detection (MID) enabled the determination of the enantiomeric distribution even for complex mixtures containing the target compounds at extremely low levels.     

顶空固相微萃取-气相色谱-质谱法测定小米黄酒风味成分

为全面了解小米黄酒风味成分的构成和气味特征,优化了85μm聚丙烯酸酯(PA)、100μm聚二甲基硅氧烷(PDMS)、75μm碳分子筛(CAR)/PDMS、50/30μm二乙烯基苯(DVB)/CAR/PDMS萃取头提取小米黄酒风味成分的条件,采用顶空固相微萃取(headspace solid phase microextraction,HS-SPME)-气相色谱-质谱法(GC-MS)对风味成分进行定性、定量分析,并计算气味活性值(odor active value,OAV),同时利用OAV分析风味成分的气味特征和气味强度。结果显示:不同萃取头的最优萃取条件为样品量8 mL、萃取时间40 min、萃取温度60℃、NaCl添加量1.5 g。小米黄酒风味成分由醇、酯、含苯化合物、烃、酸、醛、酮、烯、酚和杂环类化合物构成,醇为主要风味成分。通过OAV确定了苯乙醇、苯乙烯、2-甲基萘、1-甲基萘、苯甲醛、苯乙醛、2-甲氧基-苯酚为小米黄酒气味特征成分,苯基乙醇、苯乙醛对气味贡献最大。PA和PDMS萃取头分别对极性和非极性化合物具有较好的吸附效果,CAR/PDMS和DVB/CAR/PDMS萃取头对中等极性化合物具有较好的吸附效果。该研究全面了解了小米黄酒风味成分的构成,为其产品开发及品质控制提供理论了依据。     

Temperature requirements for thermal modulation in comprehensive two-dimensional gas chromatography

Temperature requirements for trapping and release of compounds in a cryogenic gas loop-type GC x GC modulator were determined. Maximum trapping temperatures on the uncoated, deactivated modulator capillary were determined for compounds from C4 (bp -0.5 degrees C) to C40 (bp 522 degrees C). The liquid-nitrogen cooled gas flow rate was reduced from a high of 15.5 to 1.5 SLPM over the range to achieve the required trapping temperature. Excessive cold jet flow rates caused irreversible trapping and peak tailing for semi-volatile compounds above C26. Alternate cold jet coolants were investigated. An ice water-cooled jet was able to trap compounds with boiling points from C18 (bp 316 degrees C) to C40 and a room temperature air-cooled jet was able to trap compounds from C20 (bp 344 degrees C) to C40. The hot jet produced launch temperatures approximately 40 degrees C hotter than the elution temperature with heating time constants of 8 to 27 ms. Modulated compound peaks were symmetrical with half-height peak widths of 43 to 56 ms for compounds with little second column retention, and 70 to 75 ms for compounds with more second column retention. The liquid nitrogen-cooled loop modulator with gas flow programming was used to produce a GC x GC chromatogram for a crude oil that contained compounds from C7 to C47.     

Extraction of Organic Compounds from Aqueous Media by Amberlite XAD Resins

Abstract

Three Amberlite polymeric resins, XAD-2, XAD-4 and XAD-7, were evaluated for extraction efficiency from aqueous media of several organic compounds representing pesticides, polyaromatic hydrocarbons, phenols and phthalate esters. The three resins exhibited different extraction characteristics. The extraction efficiency of the resins was found to be dependent on pH conditions and, on the average, was best at pH7. At this pH the XAD-2 and XAD-4 resins yielded quantitative recoveries in the 90–100% range for most compounds at the 20–200ppb level. Recoveries by XAD-7 resins were lower for several compounds. The recovery of aldrin and o, p DDT under all conditions was relatively low (>68%) and showed a higher degree of variability than that obtained for the other compounds. Alkaline pH conditions were generally unfavourable for the extraction of phenolic compounds but acidification to pH2 was not found to be a necessary step for the quantitative extraction of the phenolic compounds. Acidification to pH2 further led to a decrease in the recovery of most compounds for XAD-4 resins. A combined resin column yielded extraction efficiencies comparable to the XAD-2 column at pH 7, but since the three resins possess different extraction characteristics, a mixture comprising all three is recommended for the preconcentration of organic compounds from environmental water samples containing a wide range of compounds.     

Literature-based generation of hypotheses on chemical composition using database co-occurrence of chemical compounds

Candidates for identification of unknown constituents in a sample to be chemically analyzed are hypothetical. It is proposed to generate these hypotheses according to the co-occurrence of different chemical compounds with a known sample constituent in the chemical literature. The efficiency of the co-occurrence approach for predicting chemical compositions was tested for 67 impurities in 17 chemical/pharmaceutical products. The relative co-occurrence of impurity compounds and these products in the Chemical Abstracts Service database was evaluated and compared with corresponding values for several reference groups of probability sampled compounds from the literature. Almost all impurities (97%) and only < or = 8% randomly sampled compounds co-occurred with these chemical products. Mean and median values of relative co-occurrence for impurities are much higher than those of probability sampled compounds which co-occurred with the products. For the combination of impurities and the probability sample of 396 interfering compounds, the power to predict the chemical composition using the highest co-occurrences is 0.49-0.59. The co-occurrence value can also be considered as an "empiric" indicator of chemical similarity useful to generate new hypotheses on relationships both between compounds and between compounds and their properties.     

A Narrative Review of the Current Knowledge on Fruit Active Aroma Using Gas Chromatography-Olfactometry (GC-O) Analysis

Fruit aroma, a mixture of chemical compounds with odor, is a strong attractant derived from a complex mixture of different amounts and intensities (threshold) of chemical compounds found in fruits. The odor-producing compounds of fruit aroma are derived from carbohydrates, lipids, phenolic compounds, and mono- and sesquiterpenes, among others. The identification of compounds responsible for fruit aroma is usually conducted using gas chromatography coupled with olfactometry (GC-O). This technique separates the chemical compounds from the aroma of foods using a chromatographic column and divides the resultant outflow between the physical detector and a testing outlet (sniffing port). Trained judges describe the perceived odor in terms of the intensity of the odor zones perceived according to their training method. Moreover, the use of GC-O coupled with a mass detector (GC-MS-O) allows for the retrieval of chemical information such as identification and quantification of compounds, which can be correlated to sensory information. This review aimed to demonstrate the application of GC-MS-O in the identification of precursor compounds in fruit aroma, considering important factors for the application, main results, and most recent advances in this field.