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Noteworthy Chemistry

June 15, 2015


Composite bone cement keeps its cool while setting. Common treatments for painful vertebral compression fractures (a problem associated with osteoporosis) currently require injecting a poly(methyl methacrylate) (PMMA) bone cement into the fractures. As the cement polymerizes and hardens, it releases large amounts of heat, which kills the surrounding tissues.

F. Zhou, D. Qiu, Z. Yang, and colleagues at Peking University Third Hospital (Beijing), the Chinese Academy of Sciences (Beijing), Soochow University (Suzhou, China), and the University of the Chinese Academy of Sciences (Beijing) mixed paraffin-containing silica microcapsules with PMMA cement powder to form a composite material. As the cement sets, the paraffin melts and absorbs much of the heat given off by the PMMA. Enclosing the paraffin in microcapsules prevents it from leaking into the surrounding cement and tissues.

The microcapsules are compatible with the surrounding cement matrix; no gaps were observed between the microcapsules and the matrix after polymerization. The microcapsules retain their spherical shape, which demonstrates their toughness and resistance to leakage.

The composites take longer to set than plain PMMA cement, but only when the composite contains >20 wt% microcapsules (PMMA20) does the setting time become excessive for use with surgical procedures. The composite cements have significantly lower compressive strength and compressive modulus than PMMA alone. This property could be advantageous because it allows better matching of these properties between the cement and the surrounding bone material and reduces the probability of stress fractures in the bone.

Biocompatibility is similar for the PMMA20 and plain PMMA, but the composite material produces a much smaller thermal necrosis zone. In the figure, a and b are optical images of the bovine lumbar vertebrae implanted with PMMA and PMMA20, respectively. Images c and d are the corresponding coronal CT images of the necrosis zone 24 h after injection of the cement samples. The arrows point to the thermal necrosis zone and stars (★) mark the positions of implanted cements. The PMMA20-treated bone has far fewer pores than the PMMA-treated one.

Images of PMMA- and PMMA20-treated bone showing less porosity in the latter

The authors believe that composite cement that contains 20 wt% paraffin may be suitable for use in percutaneous vertebroplasty and balloon kyphoplasty procedures. They recommend that the cement be further evaluated. (ACS Appl. Mater. Interfaces DOI: 10.1021/acsami.5b01447; Nancy McGuire)

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Use a less costly protecting group when scaling up a synthesis. A. Stumpf and co-workers at Genentech (South San Francisco, CA) developed a scalable synthesis of a checkpoint kinase 1 (Chk1) inhibitor. During the synthesis, it was necessary to protect the central NH moiety in a 1,7-diazacarbazole.

In the original synthesis, the researchers used the expensive 2-trimethylsilylethoxymethyl protecting group, so for scale-up they investigated less costly options. Ethoxymethyl protection was not sufficiently selective because alkylation also occurred on a pyridine nitrogen atom (up to 36% as determined by HPLC area).

Ethoxyethyl protection was more successful, but the degree of conversion varied, and the process required as much as 18 equiv ethyl vinyl ether for full conversion. The authors attribute the variability to the low boiling point of the ethyl vinyl ether reagent (33 ºC). They therefore used propyl vinyl ether, which has a higher boiling point, as an alternative. They achieved full protection at room temperature with p-toluenesulfonic acid as the activator and tetrahydrofuran solvent. (Org. Process Res. Dev. DOI: 10.1021/acs.oprd5b00105; Will Watson)

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Levamisole promotes two transformations in a drug synthesis. BMS-986001 (1 in the figure) is a developmental candidate nucleoside reverse transcriptase inhibitor that requires a scalable synthesis. A. Ortiz and co-workers at Bristol-Myers Squibb (New Brunswick, NJ) report a route to the target molecule that uses the inexpensive organocatalyst levamisole (2).

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Double use of levamisole in a drug synthesis

A key step in the synthesis is the preparation of an enantiopure pyranone. Dynamic kinetic resolution of starting lactol 3 with several enzymes failed, so the authors used readily available levamisole in a nonenzymatic dynamic kinetic asymmetric transformation to obtain lactol ester 4 in >95% yield and 79% enantiomeric excess (ee). The enantiopurity increased to 99% ee after recrystallization.

The researchers then used levamisole as the catalyst to convert lactol intermediate 5 (prepared from 4) to furan derivative 6 via a pyranose–furanose ring chain tautomerization. This sequence, with a 44% overall yield from 4, was performed on a multigram scale. The authors plan to manufacture >250 kg 1 by this method. (Angew. Chem., Int. Ed. DOI: 10.1002/anie.201502290; José C. Barros)

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Governor orders safety measures for nail salon workers. Pregnant women may be temporarily attentive to the dangers of beauty treatments such as manicures and pedicures, but nail salon workers are continually exposed to the hazardous chemicals involved. There is accumulating evidence of a harmful link between chemicals that enhance beauty products, such as ingredients that make nail polish quick-drying and chip-resistant, and severe health problems.

The Environmental Protection Agency lists 20 common ingredients in nail products that may cause adverse health effects as a result of overexposure. Symptoms range from skin ailments and membrane irritation to central nervous system depression and respiratory problems. Worse, some chemicals are carcinogenic, and others harm reproductive health. Cosmetologists have high rates of certain cancers, and miscarriages and abnormal fetal development are common among manicurists.

In addition to acrylic powders and other chemicals, nail salon employees work extensively with

  • dibutyl phthalate (DBP), which makes nail polish pliable;
  • toluene, which lets polish glide on smoothly; and
  • formaldehyde, which allows polish to harden.

DBP is banned in cosmetics in the European Union (EU) and Australia, where it is listed as a reproductive toxicant. Toluene is a solvent that can impair kidney and cognitive function and can adversely affect a developing fetus as a result of repeated exposure. Formaldehyde is labeled as a human carcinogen in the United States and will soon be banned from cosmetics in the EU.

In response to a recent New York Times investigation, New York Governor Andrew Cuomo ordered emergency measures to protect manicurists from potentially dangerous chemicals found in nail products. Workers are now required to wear gloves to protect themselves from infectious skin conditions and chemical burns. Salons must have adequate ventilation to reduce inhalation of toxic fumes.

These measures may seem commonplace to laboratory workers, but they come too late for those in the cosmetic industry who have suffered physically and emotionally from the harmful effects of chemicals. (The New York Times; Abigail Druck Shudofsky)

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Using deep eutectic solvents could simplify leather tanning and significantly reduce the associated pollution and waste. Transforming an animal hide into supple, usable leather requires altering the proteins in the hide. The word “tanning” comes from the early use of tannins derived from tree barks and leaves.

Numerous steps are required to transform animal hides to the leather used for clothing and accessories. Each batch of hides requires days of soaking or stirring in a series of concentrated chemical solutions. One tonne of wet-salted hides produces 200–300 kg of leather, generates >600 kg of waste, and uses 30–35 m3 of water. The dyeing process uses 2000–3000 kg of water to solubilize 5 kg of dye for every 1000 kg of leather. For the most part, developed countries are capable of treating and recycling the vast quantity of waste products; that is not true in many parts of the world.

More than 150 years ago, chromium was introduced to the tanning industry to produce a very supple leather. Today ≈80–85% of leather is produced with chromium-based tanning processes. The refuse solution contains 4–6 g Cr2O3 per kilogram of hide.

A. P. Abbott and coauthors at the University of Leicester, the University of Northampton (both in UK), and Trumpler GmbH (Worms, Germany) propose the use of deep eutectic solvents (DESs) in the tanning, fatliquoring, and dyeing steps of leather production. (In fatliquoring, fats, oils, and waxes are fixed to the leather fibers.) These mixtures of quaternary ammonium halides can be used with chromium and vegetable tanning agents to ensure that active ingredients enter the hide and are fixed. They also can reduce the loss of active ingredients and dye emissions.

The authors compared the effects of using three chromium-based DESs with a conventional tanning process that uses aqueous 33% basic Cr(III) tanning salts. The DES Ethaline 200, a eutectic mixture of ethylene glycol and choline chloride, was used with two vegetable tanning processes, mimosa and chestnut bark (see figure). 

Hide tanned with mimosa or chestnut in Ethaline

The yield from the DES samples was comparable with aqueous chromium tanning; the samples also exhibited similar mechanical strength and elongation to those produced by the Cr(III) salts. With the vegetable processes, a partial volume of the ethylene glycol–choline chloride DES was retained in the leather; it may act as a built-in fatliquor or lubricant, replacing a step that follows the tanning process.

This study showed that DESs can be used satisfactorily in the tanning, fatliquoring, and dyeing processes. It supports the principle that DESs can decrease the total volume of chemicals applied during the manufacture of leather and produce minimal wastewater. The authors are continuing their research along those lines. (ACS Sustainable Chem. Eng. DOI: 10.1021/acssuschemeng.5b00226; Beth Ashby Mitchell)

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