Noteworthy Chemistry

June 6, 2011

Use boron carbide in barium-free green pyrotechnics. Barium compounds are widely used as green light emitters in military and civilian pyrotechnics. However, many barium compounds are toxic, and barium ores may contain traces of radioactive radium. Mixtures of amorphous boron and KNO3 show green emission through the formation of metastable BO2, but they burn too rapidly to be practical.

J. J. Sabatini*, J. C. Poret, and R. N. Broad at the U.S. Army installation at Picatinny Arsenal, NJ, report new boron-based formulations for emitting green light. They prepared a formulation containing KNO3 (oxidizer), amorphous boron (fuel), and a binder, and compared it with a barium-containing control. The formulation emitted light with a wavelength comparable with the control and with a higher luminous intensity. But, as expected, burning time was considerably shorter.

Next, the authors used environmentally benign boron B4C in place of amorphous boron. B4C reacts with oxygen more slowly than amorphous boron to form metastable BO2. The optimum formulation contains B4C as the only boron source: It emits a brilliant green flame and has burn times that are comparable with the barium-control. Moreover, B4C formulations are very insensitive to ignition stimuli such as impact, friction, electrostatic charge, and heat. These formulations show promise for military illuminations and commercial fireworks. (Angew. Chem., Int. Ed. 2011, 50, 4624–4626; JosÉ C. Barros)

Poly(methacrylic acid) brushes respond to pH changes. The anionic polymer poly(methacrylic acid) (PMAA) behaves differently in aqueous media when the pH value changes. The polymer chains protonate in an acidic environment and deprotonate in a base. Is this the case for all forms of PMAA?

N. SchÜwer and H.-A. Klok at EPFL (Lausanne, Switzerland) discovered that the behavior of PMAA membranes on an inert surface varies. Polymer chain length, grafting density, and chemical composition influence the response to pH fluctuations.

The authors grew the polymer brushes on the surfaces of silicon wafers or on quartz crystal microbalance chips. Polymer chain length was controlled by the living polymerization technique atom-transfer radical polymerization. Brush thickness was 5–91 nm.

In an acidic environment, the polymer is completely protonated; and the brushes remain collapsed, as indicated by the microbalance resonance frequency (see figure). As the pH is raised, the polymer deprotonates, and the brushes swell. Thicker brushes have higher pKa values, and higher density brushes begin to swell at higher pH values. Sparsely distributed polymer chains do not significantly affect these inflection points.

4-Aminophenol reacts with the PMAA brushes at pH 10. Compared with unmodified PMAA, the aminophenol-modified brushes swell at higher pH. (Langmuir 2011, 27, 4789−4796; Sally Peng Li)

A fluorogenic protein assembly detects protease and antitrypsin. Anomalous or elevated physiological levels of proteases such as trypsin are implicated in several diseases, including cancer, rheumatoid arthritis, and cardiovascular and neurodegenerative diseases. Similarly, altered α1-antitrypsin function is implicated in emphysema, liver sclerosis, and other diseases; and it has been proposed as a biomarker for early stage liver cancer.

These findings demand improved biomedical point-of-care diagnostics for proteases and their inhibitors that do not require extensive sample preparation and are less time-consuming, expensive, and error-prone than current assays. J. Ji, B. Z. Tang, and co-workers at Zhejiang University (Hangzhou, China) prepared bovine serum albumin (BSA)–tetraphenylethylene derivative conjugates with aggregation-induced emission (AIE) properties that act as effective fluorescent reporters for simple, sensitive, rapid, low-cost, label-free homogeneous detection of proteases (e.g., trypsin) and the protease inhibitor α1-antitrypsin.

The formation of the AIE bioconjugate probes is based on electrostatically induced assembly between the substituted ammonium cations of the quaternized tetraphenylethylene salt and the carboxylate anions on the BSA surface. When it is dissolved in water, the tetraphenylethylene salt shows only very weak fluorescence. The tetraphenylethylene derivative assembled on the BSA template, however, shows strong AIE amplification and achieves bright fluorescence.

In the presence of the serine protease trypsin, disintegration of the BSA–tetraphenylethylene ensemble via enzymatic hydrolytic cleavage efficiently releases the individual tetraphenylethylene units with concomitant loss of the fluorescence signal. This occurrence allows sensitive, selective detection of trypsin in concentrations as low as 5.7 μg/mL. Adding α1-antitrypsin inhibits the enzymatic activity of trypsin, preserves the AIE fluorescence, and permits sensitive detection of α1-antitrypsin.

The researchers note that the primary limitation of this method is selectivity: The probe combines with the aptamer via non–analyte-specific electrostatic forces, suggesting that other charged species may introduce interference. Overall, however, the simplicity, high sensitivity, and rapidity of the BSA–tetraphenylethylene bioconjugate assay make it a prime candidate for AIE probes for biological process monitoring and cancer diagnostics. (Analyst 2011, 136, 2315–2321; Gary A. Baker)

[Coauthor Tang is our contributor Ben Zhong Tang.—Ed.]

Prepare unusual nine-membered azlactones in one step. R. Shintami*, K. Ikehata, and T. Hayashi* at Kyoto University (Japan) report that γ-methylidene-δ-valerolactones react with N-protected aziridines in a formal [6 + 3] cyclization to form a variety of nine-membered azlactones that feature an exocyclic double bond. This family of compounds is difficult to prepare, and very few examples have been reported.

Methylene lactone 1 and p-toluenesulfonyl (Ts)–protected aziridine 2 undergo a palladium-mediated ring expansion reaction promoted by phosphoramidite ligand 3 to yield 1,4-oxazonan-9-one heterocyclic ring system 4. Yields up to 87% are obtained under optimum reaction conditions. The reaction tolerates a variety of alkyl, aryl, and functional group ring substituents.

Compounds such as 4 undergo simple methanolysis to form acyclic δ-amino acid derivatives (5) in high yield. The exocyclic double bond can also be functionalized by using a hydroboration–oxidation sequence to give the hydroxymethyl substituent shown in compound 6; 9-BBN is 9-borabicyclo[3.3.1]nonane. (J. Org. Chem. 2011, 76, 4776–4780; W. Jerry Patterson)

Use molecular design to tune mechanical properties of copolymers. S. M£lberg, A. Höglund, and A.-C. Albertsson* at the Royal Institute of Technology (Stockholm) developed a strategy for tuning biodegradation characteristics by using a copolymer architecture design that couples initial mechanical robustness with controlled, specific degradation.

The authors used bulk polymerization to synthesize elastomeric triblock polyester copolymers (~100 kDa) that have an amorphous, hydrophilic poly(2-butene-1,4-diyl malonate) (PBM) middle unit (~9.2 kDa) and semicrystalline, hydrophobic poly(L-lactide) (PLLA) or poly(ε-caprolactone) (PCL) end blocks. They observed the degradation profile of the copolymers initiated in the hydrophilic PBM block in a phosphate buffer at 37 °C and noted a reduction in elasticity at ~7 days and significantly lower mechanical function after 21 days for PLLA-PBM-PLLA than for the PLLA homopolymer.

The authors believe that the initial triblock architecture reduces to two diblocks upon hydrolytic degradation. They report that similar behavior occurs in PCL-PBM-PCL, although significant reductions in mechanical performance occur at longer times because the hydrophobic PCL block protects the PBM block from hydrolysis. These observations are supported by similar changes in molecular weight (MW): The PCL-PBM-PCL MW decreases at a slower rate than that of PLLA-PBM-PLLA.

As expected, the degree of crystallinity and the pH decrease with increasing hydrolytic exposure time. pH reduction is a function of degradation rate and is therefore slower in PCL-PBM-PCL. (Biomacromolecules 2011, 12, Article ASAP DOI: 10.1021/bm2004675; LaShanda Korley)

Make a macroring in half a day instead of several months. Macrocycles are not only esthetically pleasing, but they also can contain multiple functional groups. They are, however, difficult to synthesize. For example, preparing sterically crowded, circularly folded aromatic pentamer 1 required a months-long step-by-step process; and it was obtained in an overall yield of only ≈5% (Qin, B., et al. Org. Lett. 2008, 10, 5127–5130).

The task is much easier now; it can be accomplished in half a day by using a synthetic route developed by H. Zeng and coauthors at the National University of Singapore, Guang Dong University of Technology (China), and Nanyang Technological University (Singapore).

The protocol is based on a hydrogen-bonding–assisted, one-pot macrocyclization reaction. In the presence of coupling reagent POCl3 and organic base Et3N, 3-amino-2-methoxybenzoic acid (2) undergoes self-amidation under mild conditions to give 1 in a high yield (46%) after a 12-h reaction time. The versatility of this highly selective macrocyclization reaction is illustrated by synthesizing derivatives of 2 with various substituents at the 2- and 5-positions. (Chem. Commun. 2011, 47, 5419–5421; Ben Zhong Tang)

Optimize the synthesis of an imidazole derivative. A. C. Barros Sosa and co-workers at Roche Carolina (Florence, SC) describe a new synthesis of a 4-fluorophenylimidazole that is a key intermediate in the route to an anxiety and pain medication. Initial attempts to produce the imidazole by the reaction of N-(4-fluorophenyl)acetimidate with propargylamine were unsuccessful, but simply changing the acetimidate intermediate to an acetamidine leads to the imidazole.

Optimization of the reaction parameters showed that increasing the propargylamine loading gives higher yields of product up to a certain point, after which yields decrease. The authors followed the reaction by flow NMR and studied byproduct formation. They found that overaddition of propargylamine causes the formation of an N-propargylimidazole side product by double addition of propargylamine.

The desired reaction and the side reaction are acid-catalyzed; AcOH was used in the initial synthesis. Screening alternative acids showed that HCl gives high yields of only the desired imidazole. (Org. Process Res. Dev. 2011, 15, 449–454; Will Watson)

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