Noteworthy Chemistry

June 30, 2014

Noteworthy Chemistry is on vacation. Here are some significant items from the past year.

Use supercritical carbon dioxide to clean banknotes. Central banks around the world must dispose of ≈150,000 tons of banknotes annually at a cost of US$150 billion. The major reason for removing banknotes from circulation is soiling caused by the transfer of human sebum to note surfaces followed by oxidation that turns the notes yellow. N. M. Lawandy* and A. Smuk at Spectra Systems and at Brown University (both in Providence, RI) used supercritical CO2(scCO2) to clean banknotes and allow their reuse.

In their study, the authors used banknotes soiled during circulation and clean notes that were artificially soiled with motor oil or Bey sebum (a mixture of beef tallow and other fatty compounds) and then oxidized. They exposed the notes to scCO2 at 60 ºC and 2000 psi pressure for 16 h in a pressure vessel (see figure ). An inspection of the notes showed that the treatment removed oxidized sebum, oils, and even microorganisms; but security features such as fluorescent, magnetic, and UV light–responsive inks were not affected. The process succeeded even when the notes were wrapped with conventional 100-note straps used by banks. It works with paper and polymer banknotes.

High-pressure scCO2 cell

The authors successfully tested their process with several denominations of US dollar notes ($1, $5, $20, and $100), British pound notes, euros, Indian rupees, and Russian rubles. The method may significantly reduce central bank operating costs and mitigate the environmental impact of note disposal. (Ind. Eng. Chem. Res. 2014, 53, 530–540José C. Barros)

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This work may lead to the safe use of thalidomide. More than 50 years ago, thalidomide was used to treat morning sickness during pregnancy. Tragically, it was discovered to be a teratogen that resulted in limb and organ defects or death in the offspring. Thalidomide has since been heavily regulated, but it is being studied with the related drugs lenalidomide and pomalidomide as an antineoplastic and an immunomodulator for multiple myeloma and other B-cell malignancies.

The antitumor mechanism of these drugs, known as immunomodulatory drugs (IMiDs), is not known nor is the mechanism for their teratogenicity. It is not clear whether these activities are linked or can be separated.

Thalidomide binds cereblon, the substrate-recognition component of a cullin-dependent ubiquitin ligase. Thalidomide binding inhibits the auto-ubiquitination activity of this ligase. Zebrafish treated with thalidomide or cereblon morpholinos displayed fin defects similar to the limb defects seen in children exposed to thalidomide in utero.

Myeloma cells that are resistant to IMiDs contain downregulated cereblon, whereas those cells that are responsive to the drugs have high cereblon concentrations. This suggests that IMiDs are not cereblon antagonists, but they may change the substrate specificity of cereblon to incorporate proteins that are essential to myeloma.

W. G. Kaelin, Jr., and colleagues at Dana-Farber Cancer Institute (Boston) and Howard Hughes Medical Institute (Chevy Chase, MD) assembled a plasmid library that consisted of more than 15,000 open reading frames (ORFs) fused to firefly luciferase. They transfected each ORF into 293FT embryonic kidney cells, some of which were treated with lenalidomide. They then measured luciferase values.

Most of the ORFs were unaffected by lenalidomide treatment, but the ORFs that encode two specific B-cell transcription factors, Ikaros family zinc finger (IKZF) proteins 1 and 3, were downregulated by lenalidomide. These paralogues also were affected by pomalidomide treatment. The effects were specific: Exogenous IKZF2, -4, and -5 were not affected by IMiDs treatment; and the findings were consistent with results the authors found in other leukemic cell lines.

When cells were first treated with a small hairpin RNA (shRNA) that targets cereblon, lenalidomide did not downregulate IKZF1. Additional experiments showed that lenalidomide promotes the binding of IKZF1 and -3 (but not -2 and -5) to cereblon. Sequence analysis of IKZF1 and -2 led to the discovery that changing one glutamine residue in IKZF1 and -3 to the corresponding histidine residue in IKZF2 abrogates cereblon binding and lenalidomide-induced degradation.

This study links lenalidomide’s antimyeloma activity to the downregulation of transcription factors IKZF1 and- 3, which are critical to B-cell development and are highly expressed in B-cell malignancies. Whereas earlier research suggested that thalidomide’s teratogenic effects are caused by cereblon inactivation, the authors believe that the IMiDs’ therapeutic effects reflect a gain of cereblon function.

When cereblon is bound to lenalidomide, it targets IKZF1 and -3 for degradation. The loss of IKZF1 and -3 is necessary and sufficient for therapeutic efficacy, suggesting that it may be possible to uncouple the antitumor and teratogenic activities of the IMiDs so that these important treatments for B-cell malignancies can be used safely. (Science 2014, 343, 305–309; Abigail Druck Shudofsky)

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Vary the number of fused benzene rings to tune light emission. Luminescent molecules usually consist of rigid polynuclear aromatic rings; luminophores with flexible alicyclic rings are rare. S. Irle, S. Yamaguchi, and coauthors at Nagoya University (Japan), the Japan Science and Technology Agency (Nagoya), the University of Costa Rica (San Pedro Montes de Oca), and the Institute of Transformative Bio-Molecules/JST-CREST (Nagoya) synthesized a series of compounds (13) that have flexible cyclooctatetraene cores and rigid aceneimide wings. They found that the molecules’ luminescence properties are strongly influenced by the length of their aceneimide “wings”.

Compound 1 contains single benzene rings in its two wings. Neither its solution nor its solid emit light upon photoexcitation. When the wings contain two fused benzene rings as in 2, the solid powder is luminescent, but the dilute solution is nonemissive.

When the number of fused benzene rings is increased to three (compound 3), the solution and solid are luminescent. This remarkable tunability of light-emitting behavior may have uses in the design of multifunctional organic electronic materials. (Chem.—Eur. J2014, 20, 2193–2200Ben Zhong Tang)

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Nonemissive to fully luminescent fused ring systems

How many bubbles are in a glass of champagne? Since champagne was developed in the late 17th century, people have been amused by CO2 escaping from it in the form of bubbles. This process intrigues not only wine lovers, but scientists who want to describe it accurately. For example, people wonder about the number of bubbles in a glass.

As a result of secondary fermentation, champagne is heavily carbonated (≈11.8 g CO2/L) and bubbles spontaneously after it is poured. After using physical chemistry models to analyze the effervescence process, G. Liger-Belair at the University of Reims Champagne-Ardenne (Reims, France) derived a theoretical method for predicting the number of bubbles in a glass.

Liger-Belair first devised a theoretical model in which he simplified the situation to the release of 5 L gaseous CO2 (for a standard 750-mL bottle) from a supersaturated multicomponent aqueous alcohol system at standard temperature and pressure. Most estimates give ≈100 million bubbles in a bottle of champagne; but the author believes that this number is inaccurate because not all CO2 forms bubbles, and the bubble size is not constant during effervescence.

The author identified several parameters for determining the number of bubbles, including temperature, size of gas cavity, glass orientation while pouring, and depth of champagne in the glass (see figure). Taking into account ascending bubble dynamics and mass transfer, he calculated that ≈1 million bubbles form when 100 mL of champagne is poured straight down. Higher temperatures and pouring onto the walls of tilted glasses result in more bubbles because of the decrease in CO2 solubility and better CO2 preservation, respectively. (J. Phys. Chem. B 2014, 118, 3156–3163Xin Su)

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Height of the champagne in a glass may play a role in the number of bubbles