Noteworthy Chemistry

February 2, 2015


Trap xenon in a macrocyclic cryptand. Despite their low reactivity and low natural abundance, noble gases have important applications. Because they are so inert, it is difficult to isolate and store them by using chemical methods. But K. T. Holman and coauthors at Georgetown University (Washington, DC) and Argonne National Laboratory (Lemont, IL) report a molecular container that can trap xenon to form stable clathrates in the solid state.

Cryptophane 111 (1 in the figure) is a member of the cryptophane family of macrocyclic compounds that have cavities for encapsulating small molecules. Because 1 has a strong affinity toward xenon in solution, the authors could prepare trigonal crystalline samples of xenon contained in 1 (Xe@1). The solid retains xenon even up to 300 ºC. 

Cryptophane 111

Crystal structure analysis shows that the extraordinary stability of Xe@1 derives from noncovalent interactions between xenon and the cavity of 1, as well as from shielding by adjacent 111 units as a result of crystal packing. It is possible that selective crystallization of this form of Xe@1 can be used to separate xenon from krypton because the heavier gas does not form a cryptand that crystallizes in the trigonal phase.

Xe@1 is a rare example of a discrete molecule with excellent gas separation and storage capability. Most sorbents rely on two- and three-dimensional pores. Because the size of cryptophanes can be controlled accurately, they can potentially be developed into materials for selective adsorption of other noble gases. (Angew. Chem., Ind. Ed. DOI: 10.1002/anie.201409415Xin Su)

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Use this sensitive, low-cost method to genotype HIV drug resistance. Antiretroviral therapy is the most effective method for treating and preventing human immunodeficiency virus (HIV), but its efficacy is threatened by the emergence and proliferation of drug-resistant viruses. HIV drug resistance genotyping is a way to detect viral resistance; and it can inform clinical treatment options.

D. H. O’Connor and colleagues at the University of Wisconsin School of Medicine and Public Health (Madison), Johns Hopkins University (Baltimore), and the University of South Carolina (Columbia) introduce an updated deep-sequencing genotyping assay that uses the Illumina (San Diego) MiSeq sequencer. The team isolated and amplified HIV RNA from clinical samples, created libraries, and sequenced them using MiSeq. Analysis of the data identified viral variants.

This protocol can uniquely detect major drug resistant mutations to protease inhibitors, reverse transcription inhibitors, and integrase inhibitors at the same time with one amplicon, something that current methods cannot do. (An amplicon is a piece of DNA or RNA that is the source and/or product of natural or artificial amplification or replication events.) This assay also identifies accessory mutations, which do not confer resistance but may contribute to it.

Current FDA-approved Sanger sequencing–based HIV drug resistance genotyping methods can identify mutations that exist in >20% of the viral population of the host. In contrast, 59% of the mutations found with MiSeq are minority variants that occurred below the 20% threshold.

The HIV drug resistance genotype assay presented here is more sensitive, less error-prone, and less costly than methods currently in use. The universal primers designed by the team amplify all major group M HIV subtypes, which allows greater sensitivity. The technology allows fewer systemic sequencing errors and more accurate identification of drug-resistant mutations with homopolymer runs.

MiSeq can yield >25 million sequencing reads per run at a cost of less than $10 per sample. This method of genotyping can improve access to drug-resistance genotyping and lead to more informed clinical treatment options. (Retrovirology DOI: 10.1186/s12977-014-0122-8; Abigail Druck Shudofsky)

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Fano resonances make structural colors in thin films tunable. The iridescent "structural colors" in beetle shells, butterfly wings, and bird feathers are interference effects produced when light interacts with nanoscale structural features. Structural colors appear brighter in sunlight, do not bleach under prolonged exposure to light, and sometimes change when they are viewed at different angles.

Structural color generation generally requires choosing between structures that are thick compared to the wavelength of the light or colors that cannot be tuned dynamically. Y. Shen and coauthors at MIT (Cambridge, MA) and Johannes Kepler University (Linz, Austria) found a way to combine tunability and thin films. They prepared thin photonic crystal slabs with resonance-induced colors that stayed almost the same at all viewing angles. They tuned the colors by stretching the slabs on an elastic substrate.

The authors describe a mechanism that produces color from interference between directly reflected light and the guided resonances mode on a surface structure. This mechanism is related to Fano resonance, in which light enters a periodic surface structure and excites a one-dimensionally confined mode supported by the surface structure. This localized mode "leaks" into the surrounding environment and interferes with light directly reflected from the surface. When the reflected and radiated light are in the same phase, constructive interference produces a sharp reflectance peak.

The reflectance peak can be designed to have very weak angular dependence. The peak wavelength can be tuned by varying the periodicity of the surface structure. The authors tested their concept with arrays of lithographically produced amorphous silicon rods on a glass substrate (see figure). These samples reflected a red color that was almost uniform over a wide range of viewing angles. 

Silicon rods on a glass wafer

Because amorphous silicon absorbs in the smaller visible wavelength region, resonance was observed only for wavelengths >600 nm. The authors predict that other colors can be produced when other materials are used for the surface structures.

The authors also tested silicon rod arrays on an elastic polydimethylsiloxane substrate. This assembly process was more difficult; and the resulting samples had low macroscopic uniformity but acceptable nanoscopic accuracy. The substrate was stretched isotropically by fixing it to the surface of a balloon that was inflated gradually. Stretching the sample by 10% produced a 32-nm shift in the reflectance peak. (ACS Photonics DOI: 10.1021/ph500400w; Nancy McGuire)

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Optimize an ethenolysis reaction. D. Schweitzer* and K. D. Snell at Metabolix (Cambridge, MA) describe their investigation of the cross metathesis of crotonate esters to produce acrylate esters. In contrast to previous work, they found that ethylene is a better metathesis partner than propylene when the Hoveyda–Blechert ruthenium-based catalyst is used.

The reaction works best when run neat at room temperature with the highest possible ethylene pressure (255 psi in this study). A comparison of ethyl crotonate with n-butyl crotonate as the substrate showed that the equilibrium position is slightly more favorable with the n-butyl ester (39.6% product versus 35.8% for ethyl crotonate).

The authors believe that n-butyl crotonate has a slight advantage because it is more hydrophobic than the ethyl ester. Their explanation is supported by the observation that for a much more hydrophobic substrate, methyl oleate, the equilibrium mixture contains 94.6% product. (Org. Process Res. Dev. DOI: 10.1021/op5003006; Will Watson)

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The Zemplén reaction has been misunderstood for 90 years. Acyl groups are widely used to protect sugars. Deprotecting them is usually performed with the Zemplén reaction, a transesterification catalyzed by sodium methoxide (NaOMe) in methanol (MeOH) solvent.

H. Dong and coauthors at Huazhong University of Science & Technology (Wuhan) and Jilin University (Changchun, both in China) revisited the reaction and discovered that the traditional base-catalyzed mechanism cannot explain their laboratory results. When they used pentaacetylglucoside 1 (see figure) as a model substrate, they discovered that catalytic amounts of NaOMe (0.02 equiv) and sodium hydroxide (NaOH, 0.02 equiv) work equally well for deprotection, with quantitative yields after 4 h at room temperature. It is not necessary to use dry MeOH, as indicated by older studies. Even with 10% water in the solvent, the results were identical. 

The Zemplén deacylation reaction

The authors expanded the study to include several other acetyl-protected sugars and benzyloxycarbonyl, pivaloyl, and sulfhydryl protecting groups. The results differed only with sulfhydryl, which required 1.1 equiv NaOH. A reusable hydroxyl anion resin can be used for deacylation instead of NaOH or NaOMe.

The authors propose a mechanism that is based on hydrogen-bond complexes. It explains why methoxide and hydroxide catalyze the reaction equally well. To demonstrate that the reaction is capable of industrial use, they conducted a 10-g test that produced yields of >90%. According to the authors, their study “indicates that the Zemplén [reaction] has been misleading us for almost 90 years.” (Green Chem. DOI: 10.1039/C4GC02006E; José C. Barros)

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