Highly parallel dispensing of chemical and biological reagents

We present a technology for the highly parallel dispensing of a multitude of reagents. It allows one to dispense up to 96 different reagents simultaneously in a fixed array, in a volume range of 100 pL up to several nL. The pitch of the dispensed droplets can be as small as 500 µm. All channels are fired simultaneously, giving an unprecedented throughput. The system was originally developed for the high-throughput fabrication of microarrays, but can easily be adopted for other applications such as highly parallel filling of nanotiterplates. Based on our standard configuration we achieved droplets with 125-µm in-flight diameter (1.2 nL) with a CV of <1%.     

Ion-molecule reactions of oxygenated chemical ionization reagents with vincamine

The ion-molecule reactions of ions from acetone, dimethyl ether, 2-methoxyethanol, and vinyl methyl ether with vincamine were investigated. Reactions with dimethyl ether result in [M+13]⁺ and [M+45]⁺ products, reactions with 2-methoxyethanol produce [M+13]⁺ and [M+89]⁺ ions, and reactions with acetone or vinyl methyl ether ions generate predominantly [M+43]⁺ ions. Collision-activated dissociation and deuterium labeling experiments allowed speculation about the product structures and mechanisms of dissociation. The methylene substitution process was shown to occur at the hydroxyl oxygen and the phenyl ring of vincamine for dimethyl ether reactions, but the methylene substitution process was not favored at the hydroxyl oxygen for the 2-methoxyethanol reactions, instead favored at the 12 phenyl position. The reaction site is likely different for the 2-methoxyethanol ion due to its capability for secondary hydrogen-bonding interactions. For the [M+45]⁺ and [M+89]⁺ ions, evidence suggests that charge-remote fragmentation processes occur from these products. In general, the use of dimethyl ether ions or 2-methoxyethanol ions for ionmolecule reactions prove highly diagnostic for the characterization of vincamine; both molecular weight and structural information are obtained. Limits of detection for vincamine with dimethyl ether chemical ionization via this technique on a benchtop ion trap gas chromatography-tandem mass spectrometer are in the upper parts per trillion range.     

Alternative reagents for chemical noise reduction in liquid chromatography-mass spectrometry using selective ion-molecule reactions

Reduction of ionic chemical background noise based on selective gas-phase reactions with chosen neutral reagents has been proven to be a very promising approach in liquid chromatography—mass spectrometry (LC-MS). In this study further investigations on alternative reagents including the disulfides (dimethyl disulfide, diethyl disulfide, methyl propyl disulfide), dimethyl trisulfide, ethylene oxide, and butadiene monoxide, for example, have been carried out. Tandem mass spectrometric studies of ion/molecule reactions indicate that—besides dimethyl disulfide—ethylene oxide and butadiene monoxide also exhibit very efficient reactions with background ions. Furthermore, it is confirmed that the reactions are very selective according to the test with some analyte ions. In contrast to its rapid reactions with background ions, ethylene oxide does not react, or reacts much less, with these analytes. Therefore, it can be used as an alternative reagent for noise reduction. Although reactions of the other tested neutral reagents with background ions are evaluated, they are generally not suitable as reagents for this purpose because of lack of reactivity or dramatic ion losses during reactions.     

Calculation of the rate constants of diffusion-controlled chemical reactions for reagents of arbitrary shape

A method of describing small-size reactant diffusion in the presence of any amount of arbitrary located sinks is developed. The propagation function of mobile reagent (MR) in such a system is found. The developed method was used to calculate rate constants of bimolecular reactions of MRs with absorbents (traps) having arbitrary shape. The procedure of calculation of the rate constant has been reduced to integral equation for flux density towards a trap which is MRs' absorber. If small parameters exist, the expansion in powers of these parameters is possible. The bimolecular rates were calculated for traps of different shape. The equation was obtained which permits to determine the asymptotic time dependence of rate constants.     

Chiral nitrone reagents for cycloaddition reactions

The preparation and cycloaddition reactions of new imidazoline nitrones are described. The imidazo[1,2‐b]isoxazole alkene cycloadducts are formed via an exo approach. An example has been tranformed into a pyrrolo[1,2‐a]imidazole as a prelude to a new pyrrolidine synthesis.     

Accurate hybrid stochastic simulation of a system of coupled chemical or biochemical reactions

The dynamical solution of a well-mixed, nonlinear stochastic chemical kinetic system, described by the Master equation, may be exactly computed using the stochastic simulation algorithm. However, because the computational cost scales with the number of reaction occurrences, systems with one or more "fast" reactions become costly to simulate. This paper describes a hybrid stochastic method that partitions the system into subsets of fast and slow reactions, approximates the fast reactions as a continuous Markov process, using a chemical Langevin equation, and accurately describes the slow dynamics using the integral form of the "Next Reaction" variant of the stochastic simulation algorithm. The key innovation of this method is its mechanism of efficiently monitoring the occurrences of slow, discrete events while simultaneously simulating the dynamics of a continuous, stochastic or deterministic process. In addition, by introducing an approximation in which multiple slow reactions may occur within a time step of the numerical integration of the chemical Langevin equation, the hybrid stochastic method performs much faster with only a marginal decrease in accuracy. Multiple examples, including a biological pulse generator and a large-scale system benchmark, are simulated using the exact and proposed hybrid methods as well as, for comparison, a previous hybrid stochastic method. Probability distributions of the solutions are compared and the weak errors of the first two moments are computed. In general, these hybrid methods may be applied to the simulation of the dynamics of a system described by stochastic differential, ordinary differential, and Master equations.     

A quantum chemical study of 1,2,4-triazine reactivity in reactions with electrophilic and nucleophilic reagents

B3LYP/6-311+G(_d,p) and MP2/6-31G(_d,p) methods are used to study the electronic structure of a 1,2,4-triazine molecule. Quantitative characteristics of the reactivity are obtained in the form of atomic charges and Fukui coefficients. Thermodynamic characteristics are determined for the protonation reaction and addition of the hydride anion to a 1,2,4-triazine molecule.     

Interfacial tension controlled fusion of individual femtolitre droplets and triggering of confined chemical reactions on demand

This paper describes stepwise on-demand generation and fusion of femtolitre aqueous droplets based on interfacial tension. Sub-millisecond reaction times from droplet fusion were demonstrated, as well as a reversible chemical toggle switch based on alternating fusion of droplets containing acidic or basic solution, monitored with the pH-dependent emission of fluorescein.     

Soluble polystyrene-based sulfoxide reagents for Swern oxidation reactions

Two new soluble polystyrene-based sulfoxide reagents are introduced. These polymeric reagents are used in Swern oxidation reactions where the resulting sulfide polymers are easily separated from the product by simple precipitation and filtration. The recovered reduced polymer reagents can be recycled by oxidation with tert-butyl hydroperoxide in the presence of acid. Attempts to use these reagents in a multi-polymer Swern oxidation reaction system were unsuccessful.     

有机磷试剂在不对称反应中的应用

由于其结构多样性,有机磷化合物作为配体、催化剂、辅助剂、添加剂、底物以及试剂等在不对称反应中均获得了成功的应用,从而使有机磷试剂在不对称反应研究领域占有举足轻重的地位.本文全面介绍了本课题组近几年来围绕有机磷试剂在不对称反应中的应用,在醛的不对称硅氰化反应、内消旋环氧烷不对称开环反应、潜手性酮的不对称硼烷还原、不对称Friedel-Crafts烷基化、对映选择Mitsunobu、不对称aza-Morita-Baylis-Hillman、不对称aza-Henry以及硝基烯的不对称Michael加成反应等方面所取得的一些研究结果.     

β-Aziridinylacroleins in reactions with nucleophilic reagents

The reactivities of -aziridinylcinnamaldehyde and -(2-methylaziridinyl)acrylaldehyde with respect to amines, hydrazines, and semicarbazide were studied, -Aminoacroleins were obtained by reaction of secondary amines with aziridinylacroleins. The reaction of aziridinylcinnamaldehyde with primary amines gives the corresponding imines. It was established that in its reaction with hydrazines and semicarbazide aziridinylacrolein is more inclined to undergo heterocyclization reactions (the formation of pyrazoles and pyrazolines) than aziridinylcinnamaldehyde.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 483–488, April, 1978.     

Ring-opening reactions of benzotriazoles with Wittig reagents

Nonafluorobutanesulfonyl-1H-benzotriazole affords phenylazomethylenetriphenylphosphoranes upon treatment with in situ generated alkyl triphenylphosphoranylidenes. Methylenetriphenylphosphorylidene yields the corresponding bis-phenylazomethylene-triphenylphosphorane.     

Ultrasound-assisted method for determination of chemical oxygen demand

A method for determination chemical oxygen demand (COD) assisted by use of ultrasound has been successfully evaluated for the first time. The method uses instrumentation simpler and cheaper and, in some instances, safer than that used by previous methods for the same purpose. The new device used for sonication is an all-glass cylindrical sonotrode that can be introduced directly into the reaction mixture. Use of this device enables more efficient interaction between sample and ultrasonic energy. The optimized experimental conditions are high ultrasonic power (55% amplitude, 0.9-second pulses each second), high sulfuric acid concentration (>60%), and a sonication time of 2 min. Under these conditions the method has limitations similar to those of the official COD method with regard to the type of organic compound. It works adequately with easily oxidized organic matter (potassium hydrogen phthalate and dextrose) and other organic compounds difficult to oxidize by conventional methods (e.g. phenol and acetic acid) but the COD values obtained with volatile compounds and difficult organic matter are poor. Chloride is tolerated up to a concentration of 7000 mg L(-1) without any masking agent. Gasification of the sample is recommended to improve results; use of air and argon resulted in no significant differences - bubbling with air during sonication resulted in COD values for certified materials and real wastewater samples statistically identical with the certified COD values and those obtained by the classic (open reflux) method. The use of ultrasound energy for COD determination thus seems to be an interesting and promising alternative to conventional oxidation methods used for the same purpose.     

N-tosyloxycarbamates as reagents in rhodium-catalyzed C-H amination reactions

Metal nitrenes for use in C-H insertion reactions were obtained from N-tosyloxycarbamates in the presence of an inorganic base and a rhodium(II) dimer complex catalyst. The C-H amination reaction proceeds smoothly, and the potassium tosylate that forms as a byproduct is easily removed by filtration or an aqueous workup. This new methodology allows the amination of ethereal, benzylic, tertiary, secondary, and even primary C-H bonds. The intramolecular reaction provides an interesting route to various substituted oxazolidinones, whereas the intermolecular reaction gives trichloroethoxycarbonyl-protected amines that can be isolated with moderate to excellent yields and that cleave easily to produce the corresponding free amine. The development, scope, and limitations of the reactions are discussed herein. Isotopic effects and the electronic nature of the transition state are used to discuss the mechanism of the reaction.