Noteworthy Chemistry

March 21, 2011

Humic acids interact with mercury under anoxic conditions. Mercury can accumulate in organisms, and it is toxic in all of its oxidation states. However, the interactions between mercury compounds and natural materials are not fully understood.

B. Gu and coauthors at Oak Ridge National Laboratory (TN) and the Chinese Academy of Science (Nanjing) investigated the interactions of mercury moieties with humic acids. They found that Hg(0) and Hg(II) can react with these water- and soil-borne substances in the absence of air.

Reduced humic acids interact with Hg(II) in different ways. In aquatic ecosystems, low concentrations reduce up to 70% of the metal ions to release Hg(0) vapor. Excessive amounts of the acid, however, coordinate with Hg(II) and hinder the reduction.

Paradoxically, reduced humic acids can also oxidize Hg(0). Thiols in the acids undergo physicochemical sorption by coordinating with Hg(0) (1 in the figure). This is followed by ligand-induced oxidative complexation to produce Hg(II) complexes (2). Oxidized thiol compounds, such as disulfides, can also oxidize Hg(0). In some cases, the oxidation step occurs before complexation (second reaction sequence). (Proc. Natl. Acad. Sci. USA 2011, 108, 1479–1483; Sally Peng Li)

This efficient synthesis of diaryl ethers uses diaryliodonium salts. Developing methods for synthesizing substituted diaryl ethers has been a difficult goal to achieve. B. Olofsson and coauthors at Stockholm University and the University of Sấo Paulo (Brazil) report a method in which diaryliodonium salts (e.g., 1) are used as electrophilic agents for arylating phenols. Compound 1 is inexpensive and commercially available as the trifluoromethanesulfonate or tetrafluoroborate salt. A one-pot preparation is shown in the figure; m-CPBA is m-chloroperoxybenzoic acid, and TfOH is trifluoromethanesulfonic acid.

Treating a substituted phenol such as 2 with 1 under mild conditions produces desired diaryl ether 3 in quantitative yields in many cases. The efficiency of the reaction is underscored by the ease of forming 3 despite its highly sterically hindered structure. The reaction is tolerant to a variety of functional groups. In addition, a heterocyclic structure such as 3-hydroxypyridine—a “privileged” scaffold, according to the authors—is smoothly phenylated by this process.

This method provides iodo-substituted products that are useful for subsequent cross-coupling reactions. These products are difficult to obtain with palladium-catalyzed reactions because of chemoselectivity problems. The authors note that racemization-sensitive substrates such as tyrosine and arylglycine derivatives are arylated in excellent yields without reducing enantiomeric excess. (Org. Lett. 2011, 13, 1552–1555; W. Jerry Patterson)

Mussels inspire a method for cell protection and functionalization. I. S. Choi and coauthors at KAIST (Daejeon, Korea), the Korean Basic Science Institute (Daejeon), and Seoul National University used adhesive technology inspired by mussels to coat and modify yeast cell surfaces with polydopamine. This organic shell is noncytotoxic, can be polymerized under physiological conditions, and has reactive sites that are suitable for functionalization.

The researchers investigated single and double polydopamine-encapsulated yeast cells. The opaque, covalently bound polydopamine shells preserve the rounded-cell morphology during room temperature drying. Each encapsulating layer consists of two parts: a uniform cell wall coating and large particulates. Sequential polydopamine coating tunes the shell thickness. Cell viability is maintained after the protective coating is applied; but cell proliferation slows, as indicated by a thickness-dependent lag phase.

This strategy also improves resistance to lyticase (a yeast-cell lysis enzyme complex) during digestion. For example, ~90% of two-layer coated yeast cells are intact after 1 h, compared with <10% of native yeast cells. The authors also demonstrated a strategy for biospecific patterning and immobilization through the amine and thiol surface groups by using avidin–biotin interactions. (J. Am. Chem. Soc. 2011, 133, 2795–2797; LaShanda Korley)

A new electroluminescent device has record-breaking efficiency. Organic light-emitting diodes (OLEDs) have great potential in many applications. A research goal has been higher device efficiencies, but traditional theoretical models predict an upper limit of ~5% for the external quantum efficiency (EQE) of a singlet-based OLED. This limit was exceeded by Z.-K. Chen, J. Kieffer, and coauthors at the University of Michigan (Ann Arbor) and the Institute of Materials Research and Engineering (Singapore).

Through first-principles calculations, the researchers identified an oligofluorene (1) with an optimum molecular structure that contains electron-donating amine and electron-accepting cyano units. An OLED based on 1 gave an EQE as high as 7.4%. An even higher EQE was achieved in a doped device. By doping an appropriate amount of 1 into a suitable host, the researchers succeeded in making an OLED that emits pure blue light with an unprecedented 9.4% EQE. (Adv. Funct. Mater. 2011, 21, 699–707; Ben Zhong Tang)

Establish safe conditions for handling an unstable compound. T. J. Connolly and co-workers at Wyeth Research (Pearl River and Rouses Point, NY) describe the synthesis of 2-bromo-3-(cyclohexyloxy)acrylaldehyde (the cyclohexyl enol ether of bromomalonaldehyde) and the thermal hazard testing needed to establish safe operating conditions for scale-up. Initial studies with a thermal screening unit showed that the compound has a decomposition onset temperature of 135 °C. Additional investigation using accelerated rate calorimetry (ARC) gave a much lower decomposition onset temperature of 77 °C. Vent-sizing calculations from the ARC data in anticipation of a worst-case scenario showed that the emergency relief vent should have a 7.4-in. diam, which exceeds the 4-in. diameter vent already in the pilot plant.

Because the reaction conditions had been optimized for yield and process, the only option was to increase the solvent concentration from 25 to 31%. This gave more solvent to act as a heat sink and reduced the magnitude of the Arrhenius term, which dictates the acceleration of the heat generation rate. (Org. Process Res. Dev. 2010, 14, 1506–1511; Will Watson)

All-polymer “super” gas barriers contain multilayered thin films. The layer-by-layer (LbL) assembly technique is a well-established method for making thin films with tailored properties; for example, recently developed polymer–clay composites show exceptionally high oxygen barrier properties. Another version of this concept uses weak polyelectrolytes such as poly(ethyleneimine) (PEI) and poly(acrylic acid) (PAA) whose charges can be tailored to optimize the properties of the final composite film.

J. C. Grunlan and co-workers at Texas A&M University (College Station) modified this method by using alternating layers of 1 and 2 to form an all-polymer composite film with very low oxygen permeability. Their study resulted in a specially tailored PEI–PAA film with an oxygen transmission rate <0.005 cm3/(m2day), which the authors believe to be the lowest reported permeability of an all-polymer system.

The authors chose commercially available branched PEI 1 (Mw ~25 kDa) as the cationic polymer. It was prepared as an aqueous solution with pH adjusted to several values with HCl. The corresponding anionic aqueous polymer solution 2 was formed from commercial PAA and adjusted to the desired pH with NaOH. The LbL process was started by dipping a silicon wafer substrate into a solution of 1 for 5 min to allow adsorption of the first positively charged layer. This was followed by water-rinsing and drying steps. The substrate was then dipped in a solution of 2, followed by rinsing and drying. The remaining bilayers were formed with 1-min dip times until the target film thickness was achieved.

As the solutions were made more highly charged by appropriate pH adjustments, they underwent intrasegmental repulsions and deposited thinner layers. Conversely, weakly charged solutions resulted in thicker layers characterized by “loopy” or “coiled” surface morphologies. The films were typically cross-linked with glutaraldehyde to reduce their sensitivity to moisture. This treatment also inhibited film thickness growth by consuming the remaining free amine groups in the PEI layers.

The authors optimized the process to form eight bilayers produced from 1 at pH 10 and 2 at pH 4. The resulting composite film was 305 nm thick. Oxygen permeability of the film was <3.2 x 10–21 cm3 (STP)cm/(cm2sPa) at 23 °C and 0% relative humidity. This value is ~3 orders of magnitude lower than that of a commercial barrier film, SiOx-coated poly(ethylene terephthalate).

The authors believe that this process will be useful in making highly efficient barrier films and in other packaging applications that require high flexibility and transparency. (Macromolecules 2011, 44, 1450–1459; W. Jerry Patterson)

“Liquid cocrystals” may improve drug delivery. The search for new drugs usually involves cocrystals between an active pharmaceutical ingredient (API) and a cocrystal former (or coformer) to modulate crystal properties. The properties of a cocrystal are the result of supramolecular interactions (e.g., hydrogen bonding) between the API and the coformer. Cocrystals, however, can have the same problems as API crystals, such as polymorphism.

K. Bica, R. D. Rogers, and coauthors at the Vienna University of Technology, the Queen’s University at Belfast (Ireland), the University of Alabama (Tuscaloosa), and Monash University (Clayton, Australia) used “liquid cocrystals” to improve API performance. They chose lidocaine (1) as the API and fatty acids for the lipophilic counterions. The fatty acids were chosen because of their well-established toxicity profiles. They were classified according to their structures: short-, medium-, and long-chain (hexanoic [2], decanoic [3], and stearic [4] acids, respectively); and singly and doubly (Z)-unsaturated (oleic [5] and linoleic [6] acids, respectively).

Mixing the API with the fatty acids causes the API to liquefy; and, with the exception of stearic acid, the combination does not crystallize after mixing. The double bond–containing fatty acids perform best, as shown by the low glass-transition temperatures (<–60 °C) of their mixtures.

By using IR analysis, the authors showed that API liquefaction is caused by hydrogen bonding and not by proton transfer between the API and the fatty acid. The low ionicity of the mixtures may result in higher membrane penetration and possible uses in transdermal drug delivery or local anesthesia. Unlike solid cocrystals, the liquid compositions described in this work can have variable stoichiometries. (Chem. Commun. 2011, 47, 2267–2269; JosÉ C. Barros)

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