Noteworthy Chemistry

April 27, 2015


Charge balance gets rid of “coffee rings”. The coffee-ring effect bedevils inkjet printing, cDNA microarrays, and other technologies that rely on solvent evaporation to deposit particles uniformly onto a substrate. Suspended particles migrate to the edge of a droplet as it evaporates, producing ring-shaped deposits. Strategies used to control particle flow patterns and produce more uniform deposits include controlling particle shapes and adding cosolvents, polymers, or surfactants.

M. Anyfantakis, D. Baigl, and colleagues at Paris Sciences and Letters Research University, Pierre and Marie Curie University, and the National Center for Scientific Research (all in Paris) observed the evaporation behavior of microliter-size droplets that contained suspended solid particles and surfactants. They showed that surfactant-mediated electrostatic interactions between particles and the liquid interfaces, rather than flow patterns, determined how the particles were deposited.

When the solid particles and the surfactant have like electrical charges, the surfactant has very little influence on the particle deposition pattern. Radial evaporation-driven capillary flow dominates, and particles migrate to the edge of the droplet. When the suspended particles and the substrate (or a layer of surfactant adsorbed onto the substrate) have opposite charges, a few particles adhere to the substrate near the center of the droplet, but most of the particles are deposited in rings.

When particles and surfactant have opposite charges, however, the surfactant adsorbs onto the particle surfaces. Coffee rings persist at high and low concentrations of surfactant where the coated particles have the net electrical charge of the surfactant or of the particle, respectively. At intermediate concentrations, the surfactant charge balances the charge on the particles, making them more hydrophobic. These coated particles form a dense skin on the surface of the droplet that is not affected by radial capillary flow for most of the evaporation process. Thus, the particles are deposited as a uniform disk (see figure).

Deposits from like- and oppositely-charged systems

The authors observed this behavior in a variety of mixtures, regardless of the absolute charge and surface chemistry of the particles or the charge and hydrophobicity of the surfactants. (Langmuir DOI: 10.1021/acs.langmuir.5b00453; Nancy McGuire)

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Use electrochemistry to detect influenza viruses and to measure their susceptibility to drugs. Detecting flu viruses and determining how susceptible they are to drugs require sophisticated laboratory equipment. The absence of appropriate testing can lead to the overuse of drugs.

S. Iyer and co-workers at Georgia State University (Atlanta) developed an electrochemical device for this purpose. They first prepared a synthetic substrate, SG1 (1 in the figure), composed of N-acetylneuraminic acid (sialic acid) attached to glucose. Influenza neuraminidases can cleave this substrate and release sialic acid (2) and glucose (3), which can be detected by a standard blood glucose meter. Because glucose is absent in the healthy human nose and throat, and it is released only when neuraminidase is present, the method can be used to test nasal and throat swabs. The authors detected 19 H1N1 and H2N2 influenza strains within 1 h with this method.

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SG1 substrate cleaved by flu viruses

This method was then used to determine flu viruses’ susceptibility to neuraminidase inhibitors (zanamivir and oseltamivir) by using nasal swabs, a sample of the antiviral, and SG1. If the drug was active, it blocked the neuraminidase active site, and no glucose was detected. Because the neuraminidase inhibitors are specific for viral enzymes, adding a drug to the sample can distinguish viral enzymes from human or bacterial enzymes. The authors’ method is user-friendly, inexpensive, fast, and reliable. It should improve clinical decisions and decrease the disease burden. (Angew. Chem., Int. Ed. DOI: 10.1002/anie.201412164, José C. Barros)

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How difficult is mixing in a two-phase flow process? R. Marti and coauthors at the Institute of Chemical Technology (Fribourg, Switzerland) and Actelion Pharmaceuticals (Allschwil, Switzerland) developed a continuous-flow process for the phase-transfer–catalyzed bisalkylation of cyclopentadiene with 1,2-dichloroethane mediated by aqueous sodium hydroxide. Their process improves the yield by almost three-fold.

Using a simple T-mixer gave a best yield of 32% for the bisalkylation. This result could be increased to 56% by using a better mixing unit (LTF-MX), but the authors saw that after initial good mixing, the two phases soon separated and slug flow ensued. Improving the mixing by the adding another mixer (LTF-MS) in front of LTF-MX did not improve the yield. But when the researchers placed an LTF-VS residence time unit with an integrated snake mixer unit between two LTF-MX mixers, the yield increased to 75%.

A final optimized yield of 95% was achieved by increasing the amount of alkylating agent and phase-transfer catalyst and introducing a temperature ramp. All of the LTF units were purchased from Little Things Factory (Ilmenau, Germany). (Org. Process Res. Dev. DOI: 10.1021/acs.oprd.5b00046; Will Watson)

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Limonene cross-links polysiloxane-based luminescent films. D-Limonene, a small-molecule cyclic terpene, helps give lemons and other citrus fruits their distinctive odor. Limonene is widely used in cosmetics and cleaning products, but it is rarely used for synthesizing chemicals and materials.

With its two isolated C=C bonds, limonene can be used as a cross-linker in the thiol–ene click reaction. Taking advantage of this technique, Y. Zuo, J. Cao, and S. Feng* at Shandong University (Jinan, China) designed and prepared polysiloxane-based luminescent films that can be cross-linked under sunlight in the presence of limonene.

The researchers first ran a model reaction with limonene (1) and 1-dodecanethiol (2; see figure). It yielded only diaddition products (3) in the presence of a radical initiator, which validated the efficacy of limonene as a cross-linker. They then attached various side chains, including an allylrhodamine group, to poly[(mercaptopropyl)methylsiloxane] (PMMS) via thiol–ene coupling. The products’ fluorescence emission color could be tuned from blue to red. The modified PMMS structures were then cross-linked with limonene to form emissive films.

Reaction of 1-dodecanethiol and limonene to give diaddition products

The cross-linking step can be carried out directly by using sunlight. In addition, a mixture of modified PMMS and limonene can be applied to ultraviolet light-emitting diode surfaces and cross-linked in situ to give colorful LED cells. Other films and molded devices can be prepared similarly.

This strategy simplifies the preparation of emissive solids with tunable luminescent properties through simple and traceless operations. Limonene is volatile and leaves no residue to compromise the integrity and strength of the objects. (Adv. Funct. Mater. DOI: 10.1002/adfm.201500187; Xin Su)

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Make 2,2-difluorodiazoethane in situ for pyrazole synthesis. Fluorinated compounds are present in 20% of all drugs and agrochemicals. Several fluorinated building blocks are used to make these compounds, but 2,2-difluorodiazoethane (CHF2CHN2, 2 in the figure) has not been one of them until now.

P. K. Mykhailiuk at Enamine (Kyiv, Ukraine) and Taras Shevchenko National University of Kyiv developed a straightforward synthesis of CHF2CHN2. Taking his cue from the in situ preparation and reactions of the parent molecule 2,2,2-trifluoroazoethane reported by B. Morandi and E. M. Carreira at ETH Zurich (Switzerland)*, he attempted, but failed, to prepare the desired molecule from 2,2-difluoroethylamine (1) and aqueous sodium nitrite. He believes that the aqueous environment and basic NaNO2 contribute to degradation of the product.

In situ formation of CHF2CHN2 for pyrazole synthesis

The author then changed the diazotization system to organic tert-butyl nitrite (t-BuONO) in the presence of acetic acid catalyst in chloroform to obtain a deep yellow solution of CHF2CHN2. The difluoro diazo compound reacts with alkynes (3) to produce pyrazoles (4) via a [3 + 2] cycloaddition reaction.

Mykhailiuk tested several mono- and disubstituted alkynes and observed that substrates that contain electron-withdrawing groups give good yields. The reaction is regiospecific when monosubstituted alkynes are used because only 3,5-disubstituted pyrazoles are obtained. The reaction is practical and scalable and avoids the isolation of potentially toxic and explosive CHF2CHN2, which makes it useful as a building block in organic and medicinal chemistry. (Angew. Chem., Int. Ed. DOI: 10.1002/anie.201501529, José C. Barros)

[The article refers to 2,2-difluorodiazoethane as “difluoromethyl diazomethane”.—Ed.]

*Angew. Chem., Int. Ed. DOI: 10.1002/anie.200905573

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