Noteworthy Chemistry

November 19, 2012

Measure enantiopurity with a stereodynamic sensor. Induced circular dichroism (ICD) is a chiroptical spectroscopic technique that detects chiral compounds via the Cotton effects generated by their interactions with stereodynamic sensors. Using chiroptical spectroscopy to determine enantiomeric excess is faster and more efficient than chromatographic methods. D. P. Iwaniuk and C. Wolf* at Georgetown University (Washington, DC) demonstrated the advantages of chiroptical spectroscopy by developing a chromophoric stereodynamic sensor to determine the enantiopurity of citronellal, a chiral but “CD-silent” aldehyde.

The authors formed the stereodynamic sensor on an arylacetylene backbone. They first attached two bromobenzene units to diethynylbenzene (1) via a double Sonogashira coupling with o-iodobromobenzene (2). Intermediate 3 was then coupled with 2-ethynylaniline (4) to give bisaniline sensor 5 in 44% overall yield. Compound 5 has free internal rotation about the C≡C bonds; because of the low rotation barriers, its conformers cannot be resolved at room temperature.

As expected, free 5 is CD-silent in solution. When it is condensed with 2 equiv citronellal (6), however, the adduct exhibits strong ICD signals. In addition, the CD signals of the adducts of 5 with (R)-6 and 5 with (S)-6 are mirror images of each other.

The authors established a calibration curve based on the linear correlation between the CD amplitudes at 400 nm and the enantiomeric excess of 6. The curve spans a broad range of the ee values with high accuracy. Unexpectedly, 5 is chemoselective; it cannot react with α-branched aldehydes—possibly because of its inherent steric hindrance. (Chem. Commun. 2012, 48, 11226–11228; Xin Su)

Use living materials as antibiotic-releasing surfaces. Medical devices and surfaces with preloaded active ingredients and controlled release have many uses. But these “smart” materials usually contain a fixed supply of active ingredients that depletes quickly.

W. J. Stark and co-workers at ETH Zurich previously created a living material suitable for fungus growth (Gerber, L. C., et al. Proc. Natl. Acad. Sci. USA 2012, 109, 90–94). The material consists of a living agar layer sandwiched between a polymer bottom layer and a nanoporous polyacrylate membrane. Fungi are kept alive in the material by feeding them with nutrients that diffuse through the porous top layer.

To test potential antibacterial applications of the living material, the authors incorporated the penicillin-producing fungus Penicillium chrysogenum into the agar layer. The treated material killed surface-applied, penicillin-sensitive Staphylococcus carnosus bacteria in <1 day.

The living material needs structural improvements, such as preventing the agar layer from drying out too quickly. Incorporating other organisms may lead to a variety of applications. (Angew. Chem., Int. Ed. 2012, 51, 11293–11296; Chaya Pooput)

The order of reagent addition affects thermal safety. I. S. Young and colleagues at Bristol-Myers Squibb (New Brunswick, NJ) developed an alternative route to (−)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol, an intermediate in the synthesis of a potential lung cancer drug. In one step of the synthesis of the intermediate, N-benzylpyridinium chloride can be reduced by NaBH4 in EtOH by adding a NaBH4 solution to a solution of the pyridinium salt or by adding the pyridinium salt solution to a NaBH4 solution.

Thermal hazard testing showed that adding ethanolic NaBH4 to a solution of the pyridinium salt in EtOH at 10 °C generates 79 J of heat within 6 min. When the addition order is reversed, the total heat of reaction is 464 J, and the exotherm is self-sustaining for 140 min. The authors showed that catalysis of the exothermic decomposition of NaBH4 by the N-benzyltetrahydropyridine reduction product is responsible for the difference in the heats of reaction. (Org. Process Res Dev. 2012, 9, 1558–1565; Will Watson)

Aliphatic rings strongly affect the luminescence behavior of organoboron complexes. Boron dipyrromethene (BODIPY, 1), a well-known planar aromatic organoboron complex, luminesces efficiently in solution but poorly in the solid state. Organoboron complexes with nonplanar aliphatic rings behave very differently, as shown by K. K. Balasubramanian, K. Venkatesan, and coauthors at the University of Zurich, Shasun Research Center (Chennai, India), Annamalai University (Chidambaram, India), and B. S. Abdur Rahman University (Chennai).

The authors’ complexes (2) are β-iminoenamineboron difluoride molecules with alicyclic or heteroalicyclic rings. Unlike BODIPY, compounds with structure 2 emit more efficiently in the solid state than in solution. The authors believe that dynamic conformational motion in the individual molecules nonradiatively quenches luminescence in solution. Strong CH–F and CH–π interactions in the crystalline complexes create rigid molecular structures, block the nonradiative decay pathway, and make the complexes luminescent in the solid state. (Chem. Asian J. 2012, 7, 2670–2677; Ben Zhong Tang)

Supramolecular interactions drive imaging agent design. M. Elsabahy, Y. Liu, K. L. Wooley, and colleagues at Texas A&M University (College Station), Washington University (St. Louis), and Assiut University (Egypt) used a hierarchical technique to produce a nanostructured silencing RNA (siRNA) delivery vehicle with imaging capabilities. Cationic shell cross-linked knedel (dumpling)–like nanoparticles (cSCKs; ≈20 nm diam) and anionic shell cross-linked cylindrical rods (SCRs, 10 nm diam, 1.5 μm long) were co-assembled in a 10:1 amine/carboxylate ratio to yield positively charged, nanostructured rods with a layer of spherical cSCKs.

siRNA complexes with the supramolecular assemblies by electrostatically interacting with the “decorated” cSCKs, which have higher binding efficiencies than individual cSCKs. At an amine/photodiester ratio of 5:1, the siRNA-complexed, hierarchically assembled nanostructures exhibit cellular uptake and stimulate greater transfection efficiency than cSCKs alone. The authors attribute these improvements to increased contact time between cells and siRNA caused by multivalent binding interactions. The nanostructures also have substantial radiolabeling capabilities for theranostic applications . (J. Am. Chem. Soc. 2012, 142, 17362–17365; LaShanda Korley)

How do proteins discriminate between phosphate and arsenate? Phosphate and arsenate are similar anions: Both are triply charged, their pKa values are almost identical, and their thermochemical radii differ by only 4%. They have very distinct physiological properties, however: Arsenate is toxic, whereas phosphate is a necessary ingredient for life.

Because both anions are abundant in nature, life forms must discriminate between them. M. Elias, A. Wellner, and coauthors at the Weizmann Institute of Science (Rehovot, Israel), CNRS–University of the Mediterranean (Marseille, France), and ETH Zurich showed that phosphate-binding proteins (PBPs) in bacterial cells exhibit high selectivity toward phosphate over arsenate and identified them as the key factor for molecular-level discrimination.

The authors studied five proteins from various sources, including a highly arsenate-resistant bacterium (Halomonas strain GFAJ-1). Four of the PBPs had phosphate/arsenate selectivities of 500−850-fold, but the phosphate selectivity of PBP-2 from Halomonas GFAJ-1 was >4500-fold.

The researchers then compared the sub-£ngström–resolution structures of arsenate- and phosphate-bound Pseudomonas fluorescens PBP (PfluDING). The two structures can be superimposed almost perfectly, but there is a significant difference between the strong hydrogen bonds between the carbonate group of Asp 62 and the anions’ protonated O2 atoms. These low-barrier hydrogen bonds have the same donor–acceptor distance (2.50 Å) in both structures. The three hydrogen-bonding angles, however, are optimal in phosphate-bound PfluDING; all three are distorted in the arsenate structure.

The authors conclude that this hydrogen bond is the interaction that determines selectivity to phosphate over arsenate. This study also provides evidence for the theory that PBPs evolved to accommodate high arsenate levels. (Nature 2012, 491, 134–137; Xin Su)

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