Noteworthy Chemistry

February 4, 2013

These smart polymers shatter instead of unraveling. Biocompatible “smart” polymers are increasingly used for drug delivery. They are sensitive to various external stimuli (e.g., temperature, pH, and light) that cause their chemical structure to collapse.

So-called self-immolating smart polymers have stimulus-sensitive groups at the chain ends where the decomposition begins. Degradation then spontaneously propagates through the polymer chain. J. Cheng and co-workers at the University of Illinois at Urbana–Champaign developed an alternative type of polymer in which multiple reactive units are embedded in the polymer’s backbone.

“Chain-shattering polymers” (CSPs) 1, 2¸ and 3 contain 2, 6-disubstituted aniline units that are decomposed by UV light, acid, and base, respectively. To prepare the polymer structures, the authors used difunctional compounds 4 and 5 as comonomers. The desired polymers are made by polycondensation.

When a stimulus is applied, the sensitive groups decompose to break the polymer’s backbone. Every repeat unit eventually decomposes. Trials on the controlled release of dye- and drug-containing polymer nanoparticles showed that the encapsulated molecules release rapidly and controllably. The authors expect CSPs to be useful in burst-release applications. (Polym. Chem. 2013, 4, 224–228; Sally Peng Li)

Nanothermometers light up in a desired temperature range. Medical thermometers precisely measure human body temperature, but they do not work on the sub-millimeter scale needed for procedures such as thermal tumor ablation. To tackle this challenge, M. Y. Berezin and colleagues at the St. Louis School of Medicine created thermally responsive, fluorescent nanocomposites.

The authors targeted the 60–80 °C temperature range, in which tumor cells would be killed instantly. They began by making gold nanorods for the composites’ core, which they prepared in the presence of cetyltrimethylammonium bromide (CTAB) by a seed-mediated synthesis. They exchanged CTAB with mPEG2000 thiol, which they then replaced with cysteine-rich peptide–coumarin dye conjugates without altering the core’s shape or size. The key component in the nanocomposite design is the peptide linker, which holds the dye close to the gold nanorods via Au−S bonds. These bonds dissociate at <100 °C in aqueous media.

Because the coumarin dye is attached to the gold surfaces by the peptide linker, it undergoes aggregation-caused quenching and does not fluoresce. When the nanocomposites are heated to >70 °C, however, the Au−S bonds break irreversibly. The ablated dye regains its fluorescence and can be used to indicate temperature changes in this range. (Chem. Commun. 2013, 49, 680–682; Xin Su)

Use acidic fluoro alcohols for solid-phase peptide deprotection. Peptides for medicinal applications usually are produced by a solid-phase synthesis that uses the 9-fluorenylmethoxycarbonyl (Fmoc) method. In this technique, an acid is used to remove acid-labile protecting groups and liberate the peptide from the resin. Trifluoroacetic acid (CF3CO2H), which is usually used in this reaction, is toxic, extremely corrosive, and expensive to purchase and dispose.

P. Palladino and D. Stetsenko* at the University of Reading (UK) replaced CF3CO2H with HCl in the presence of acidic fluoro alcohols such as 2,2,2-trifluoroethanol (CF3CH2OH or TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol [(CF3)2CHOH or HFIP]. They protected several Fmoc-modified amino acids with acid-labile groups and then treated them with HCl–fluoro alcohol mixtures, neat or in the presence of cosolvents. The results showed that 0.1 M HCl in neat HFIP is the best combination for rapid, complete deprotection.

Commonly used protecting groups (e.g., tert-butyl [t-Bu], tert-butoxycarbonyl [BOC], trityl [Trt], and highly resistant pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl [Pbf]) were removed with excellent yields. No Fmoc deprotection occurred in any experiment.

The authors also applied their method to cleaving acid-labile resin linkers such as trityl ester, Wang, hexamethylphosphoramide, Rink amide, and phenylalanine ammonia lyase. They prepared a collagen-stimulating peptide, Fmoc-KTTKS-OH, on a TentaGel S Trt resin and cleaved the resin in high purity in 12 h, as indicated by electrospray ionization high-resolution mass spectrometry. (Org. Lett. 2012, 14, 6346–6349; José C. Barros)

Superomniphobic hierarchical surface coatings act as chemical shields. A. Tuteja and coauthors at the University of Michigan (Ann Arbor) and Edwards Air Force Base (CA) developed a hierarchically assembled surface that exhibits “superomniphobicity”—a combination of superhydrophobicity and superoleophobicity. They formed the surfaces by electrospinning a blend of cross-linked polydimethylsiloxane (PDMS) with 50 wt% fluorodecyl polyhedral oligomeric silesquioxane (POSS) onto a stainless steel wire mesh. The low–surface energy coating had low contact-angle hysteresis and small roll-off angles for a range of Newtonian and non-Newtonian fluids.

The hierarchical coatings resist macroscopic and microscopic chemical damage. They prevent corrosion of aluminum plates and inhibit typical swelling behavior of PDMS when they are exposed to solvents such as toluene and chloroform. The surfaces do not reconfigure when exposed to enthalpically favorable solvents. (J. Am. Chem. Soc. 2013, 135, 578–581; LaShanda Korley)

A simple fluorogen emits bright red light in the solid state. Red-light emitters are in great demand, especially in optoelectronics and biomedical research. The fluorescence from such emitters is often quenched in the solid state, however, because of the aggregation-caused quenching (ACQ) effect. Y. S. Zhao, W. Zhu, and coauthors at East China University of Science and Technology (Shanghai) and the Chinese Academy of Sciences (Beijing) developed a fluorogenic molecule (1) with a relatively simple structure that emits red light efficiently in the solid state.

Intriguingly, 1 does not emit in the solution state. Its films and powders are fluorescent and exhibit unusual aggregation-induced emission (AIE). The researchers designed and prepared a control compound (2) with a similar but planar structure that has a typical ACQ effect. By comparing 1 and 2, they deduced that dynamic intramolecular rotations of the aromatic rotors in 1 quench its fluorescence in the solution state, whereas restricting such rotation by aggregate formation makes it AIE active.

The molecules of 1 self-assemble into nanorods that show excellent waveguide properties with low optical loss. Their emission responds to stimuli; the color can be tuned by grinding and fuming or pressing and heating.

Nanoaggregates of 1 can be used to stain cytoplasm. Its red fluorescence makes it attractive for bioimaging applications because it circumvents interference from UV-induced autofluorescence and phototoxicity. (ACS Appl. Mater. Interfaces 2013, 5, 192–198; Ben Zhong Tang)

Choose the safest solvent for a sodium metal reduction. R. A. Breitenmoser*, T. Fink, and S. Abele at CARBOGEN AMCIS AG (Bubendorf, Switzerland) found that sodium in alcohol was the best reagent for reducing 2-allylcyclohexanone oxime to trans-2-allylcyclohexylamine. Their original procedure required the addition of a large excess of solid sodium to a refluxing EtOH solution.

The authors then discovered that melting sodium in a high-boiling nonpolar solvent (mixed xylenes) before adding the substrate and alcohol was a safer option. This procedure required an alcohol with a boiling point higher than the melting point of sodium. The authors chose 4-methyl-2-pentanol to replace EtOH.

The process was developed on a pilot scale, but safety testing showed that the plant could not cope with the high rate of heat evolution. The researchers overcame this problem by using a 1:1 w/w mixture of toluene and xylenes. This change allows the reaction to be carried out at reflux, increasing the cooling capacity of the system. (Org. Process Res. Dev. 2012, 16, 2008–2014; Will Watson)


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