New method to determine the total carbonyl functional group content in extractable particulate organic matter by tandem mass spectrometry

A functional group analysis method was developed to determine the quantitative content of carbonyl functional groups in atmospheric particulate organic matter (POM) using constant neutral loss scanning-tandem mass spectrometry (CNLS-MS/MS). The neutral loss method consists in monitoring the loss of a neutral fragment produced by the fragmentation of a precursor ion in a collision cell. The only ions detected are the daughter ions resulting from the loss of the neutral fragment under study. Then, scanning the loss of a neutral fragment characteristic of a functional group enables the selective detection of the compounds bearing the chemical function under study within a complex mixture. The selective detection of carbonyl functional groups was achieved after derivatization with pentafluorophenylhydrazine (PFPH) by monitoring the neutral loss of C(6)F(5)N (181 amu), which was characteristic of a large panel of derivatized carbonyl compounds. The method was tested on 25 reference mixtures of different composition, all containing 24 carbonyl compounds at randomly determined concentrations. The repeatability and calibration tests were satisfying as they resulted in a relative standard deviation below 5% and a linear range between 0.01 and 0.65 mM with a calculated detection limit of 0.0035 mM. Also, the relative deviation induced by changing the composition of the mixture while keeping the total concentration of carbonyl functional groups constant was less than 20%. These reliability experiments demonstrate the high robustness of the developed procedure for accurate carbonyl functional group measurement, which was applied to atmospheric POM samples.     

Spectral signatures and molecular origin of acid dissociation intermediates

The existence of a broad, mid-infrared absorption ranging from 1000 to 3000 cm(-1) is usually interpreted as a signature for the existence of protonated water networks. Herein, we use cryogenic mixtures of water and hydrogen fluoride (HF) and show experimental and computational evidence that similarly wide absorptions can be generated by a broad distribution of proton-shared and ion pair complexes. In the present case, we demonstrate that the broadening is mainly inhomogeneous, reflecting the fact that the topology of the first solvation shell determines the local degree of ionization and the shared-proton asymmetric stretching frequency within H2O x HF complexes. The extreme sensitivity of the proton transfer potential energy hypersurface to local hydrogen bonding topologies modulates its vibrational frequency from 2800 down to approximately 1300 cm(-1), the latter value being characteristic of solvation geometries that yield similar condensed-phase proton affinities for H2O and fluoride. By linking the local degree of ionization to the solvation pattern, we are able to propose a mechanism of ionization for HF in aqueous solutions and to explain some of their unusual properties at large concentrations. However, an important conclusion of broad scientific interest is our prediction that spectral signatures that are normally attributed to protonated water networks could also reveal the presence of strong hydrogen bonds between un-ionized acids and water molecules, with important consequences to spectroscopic investigations of biologically relevant proton channels and pumps.     

Reaction rates as a function of scale within ionic liquids: microscale in droplet microreactors versus macroscale reactions in the case of the Grieco three-component condensation reaction

Task-specific ionic liquids (TSILs) and more specifically binary task-specific ionic liquids (BTSILs), a unique subclass, have been shown to be excellent supports for solution-phase chemistry. The negligible volatility of ionic liquids enables their use as stable droplet microreactors in atmospheric environments without oil protection or confinement. These droplets can be moved, merged and mixed by electrowetting on a chip. Solution-phase synthesis can be performed on these open digital microfluidic labs-on-a-chip as illustrated by a study of the Grieco three-component reaction in [tmba][NTf(2)]-droplet (tmba=N-trimethyl-N-butylammonium NTf(2)=bis(trifluoromethylsulfonyl)imide) microreactors. A detailed study of matrices and scale effects on conversion and kinetic rates of this three-component condensation is presented in this paper. Reactions have been shown to be slower in droplets than in batches in the absence of additional mixing. Also, a significant influence of the ionic-liquid matrix has been observed. Finally, an increase of droplet's temperature resulted in a kinetics enhancement so as to reach macroscale reaction rates, probably because of a much better mixing of reaction's components involving a Marangoni's effect.     

Carboxylic acid functional group analysis using constant neutral loss scanning-mass spectrometry

The present study describes the development of a new analytical technique for the functional group determination of the carboxylic moiety using atmospheric pressure chemical ionization-mass spectrometry (APCI-MS/MS) operated in the constant neutral loss scanning (CNLS) mode. Carboxylic groups were first derivatized into their corresponding methyl esters by reacting with BF₃/methanol mix and the reaction mixture was then directly injected into the APCI chamber. The loss of methanol (m/z = 32 amu) resulting from the fragmentation of the protonated methyl esters was then monitored. Applying this method together with a statistical approach to reference mixtures containing 31 different carboxylic acids at randomly calculated concentrations demonstrated its suitability for quantitative functional group measurements with relative standard deviations below 15% and a detection limit of 0.005 mmol L⁻¹. Its applicability to environmental matrices was also shown through the determination of carboxylic acid concentrations inside atmospheric aerosol samples. To the best of our knowledge, it is the first time that the tandem mass spectrometry was successfully applied to functional group analysis, offering great perspectives in the characterization of complex mixtures which are prevailing in the field of environmental analysis as well as in the understanding of the chemical processes occurring in these matrices.     

Synthesis of a novel cage-functionalized chiral binaphthol host: a potential new agent for enantioselective recognition of chiral ammonium salts

Optically active, cage-functionalized crown ether (R)-3 which contains a 1,1′-bi-2-naphthol moiety has been prepared. Subsequently, the ability of (R)-3 to selectively recognize the enantiomers of guest ammonium salts, i.e., 4 and 5 in transport experiments was studied. Host (R)-3 displays significantly enhanced enantiomeric selectivity toward complex formation with 4 vis-à-vis complex formation with 5. The relative energetics of various relevant host–guest complexes have been investigated computationally.     

The 0-1 Knapsack problem with a single continuous variable

Specifically we investigate the polyhedral structure of the knapsack problem with a single continuous variable, called the mixed 0-1 knapsack problem. First different classes of facet-defining inequalities are derived based on restriction and lifting. The order of lifting, particularly of the continuous variable, plays an important role. Secondly we show that the flow cover inequalities derived for the single node flow set, consisting of arc flows into and out of a single node with binary variable lower and upper bounds on each arc, can be obtained from valid inequalities for the mixed 0-1 knapsack problem. Thus the separation heuristic we derive for mixed knapsack sets can also be used to derive cuts for more general mixed 0-1 constraints. Initial computational results on a variety of problems are presented. Received May 22, 1997 / Revised version received December 22, 1997 Published online November 24, 1998     

Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases

Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b,d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC₅₀ value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure–activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.     

Diisothiocyanates as heterodienophiles or dipolarophiles in the presence of α‐thioxothioamides or mesoionic thiazoles

Reactions of α‐thioxothioamides ( 1 ) with diisothiocyanates were carried out in the hope of generating the N,N′‐bis(1,3‐thiazoline‐2‐thiones) ( A ). Although that purpose could not be achieved, we succeeded in preparing the monocycloadducts 7 from the phenylene‐1,2‐diisothiocyanate ( 4 ). The benzimidazole derivatives 8 and 9 were also characterized and a mechanism was assumed to account for this intramolecular process. On the other hand, the regioselective synthesis of the N,N′‐biimidazole ( 13 ) containing the phenylene bridge was performed by the treatment of the 5‐aminothiazolium chloride ( 2 ) with the diisothiocyanate ( 4 ) in a basic medium. The mesoionic derivative 13 probably arises from the monoimidazolium‐4‐thiolate ( 12 ) which was shown to react with the salt 2 under similar conditions to give the primary cycloadduct 14 as an intermediate towards the bis(imidazolium) ( 13 ). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:617–624, 2001     

Addition of isocyanides to α‐(methylthio)‐benzylidenamidinium iodides: A surprising access to 2‐(dialkylamino)imidazoles and 3,5‐diamino‐2H‐pyrrolium salts

A number of 2‐(dialkylamino)‐5‐(methylthio)imidazoles 2 are obtained by treating the formamidinium iodides 1a,b with isocyanides R³ NC under mild conditions. Reduction of these species can occur in the reaction medium to furnish the corresponding imidazoles 3 . In some cases, double cycloaddition across the imine bond of starting salts 1 also provides the (azetidin‐1‐yl‐methylene)ammonium iodides 4 . Reactions with tert‐butyl and isopropyl isocyanides in refluxing acetonitrile convert the acetamidinium iodide 1c into the 3,5‐diamino‐2H‐pyrrolium salts 7 . Mechanisms are suggested to account for these ring‐closure processes. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:370–376, 2000