Noteworthy Chemistry

March 16, 2015


A β-diketone luminogen shows multiple chromic effects. Organic luminogens, especially those with sensitive, reversible responses to stimuli, are promising materials for high-tech applications in optics and optoelectronics. C. L. Fraser and fellow researchers at the University of Virginia (Charlottesville) synthesized an organic luminogen (1) with light emission that is tunable by solvent polarity, chromophore aggregation, and mechanical force.

Thus compound 1, shown as its enol tautomer in the figure, exhibits a unique combination of solvato-, aggregato-, and mechanochromism.

β-Diketone (in its enol form) with multiple chromic effects

The luminescence of 1 in solution red-shifts and intensifies when the solvent polarity is increased. Its emission in tetrahydrofuran increases by >5-fold when its molecules aggregate in a 30:70 THF/water mixture. When the powder of 1 is mechanically smeared, its emission intensifies, with a contrast ratio as high as ≈23:1.

The authors believe that these multiple chromic effects may make it possible to use 1 in fluorescent sensors, security inks, shape memory materials, and light-emitting diodes. (Chem. Commun. DOI: 10.1039/C4CC09439E; Ben Zhong Tang)

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Simplify cofactor regeneration during biocatalytic reduction. Biocatalytic ketone reduction has become a powerful synthetic tool, but it normally requires additional reagents or enzymes to regenerate the cofactor, typically NADH or NADPH*. S. Kara and coauthors at CHIRACON GmbH (Luckenwalde, Germany), Evocatal GmbH (Monheim am Rhein, Germany), Delft University of Technology (The Netherlands), and the Technical University of Dresden (Germany) describe the scale-up of a “smart cosubstrate” enzymatic reduction on which cofactor regeneration is significantly simpler.

The authors used a half-molar equivalent of the cosubstrate, 1,4-butane diol. This allows the cofactor to regenerate when the alcohol dehydrogenase enzyme is used for reducing the substrate (ethyl 4,4,4-trifluoroacetoacetate in this case).

The system produces a high enantiomeric excess (>99%) of the (S)-alcohol with good purity (94%), but the reaction takes 5 days to go to completion. An added complication is the need for fractional distillation to separate the product from the γ-butyrolactone byproduct. (Org. Process Res. Dev. DOI: 10.1021/op500374x; Will Watson)

*Nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate, respectively.

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Are adrenaline and noradrenaline protectors or targets? The answer is “both”, according to R. Álvarez-Diduk and A. Galano* of the Metropolitan Autonomous University–Iztapalapa (Mexico City). They used density functional theory calculations to investigate the roles of these catecholamine neurotransmitters (also known as epinephrine and norepinephrine) in organisms under oxidative stress, a condition associated with numerous human health and development disorders.

Adrenaline’s role as a radical scavenger and metal chelator makes it an efficient antioxidant. Noradrenaline has been reported to provide short-term protection against β-amyloid–induced neurotoxicity associated with Alzheimer’s disease; it also reduces the amounts of reactive oxygen species within cells, which might be useful for treating Parkinson’s disease. Accumulations of the reaction products in the body, however, could pose a health risk.

The computational study predicts that adrenaline and noradrenaline can be efficient free-radical scavengers in lipids and aqueous media. The two compounds react with peroxyl radicals (•OOH) faster than the reference compound trolox (a water-soluble analogue of vitamin E), but they only partially inhibit oxidative stress induced by hydroxyl radicals (•OH) produced by the copper-catalyzed reaction of hydrogen peroxide with oxygen radicals (O2•–). Their ability to sequester copper(II) ions by forming chelation complexes makes them efficient against Cu(II)–ascorbate mixtures.

The figure shows the mechanism of the free-radical–scavenging activity and regeneration of adrenaline (1, R = Me) and noradrenaline (1, R = H).

Mechanism of free-radical–scavenging activity and regeneration of adrenaline and noradrenaline

Under highly oxidative conditions, both compounds may lose their functionality as a result of their antioxidant activities, making them molecular targets. Under physiological conditions, both can be regenerated spontaneously and resume their activity unless the intermediates are consumed in reactions with other species.

Cyclic 3-hydroxymelatonin, a melatonin metabolite, forms particularly strong complexes with Cu(II), which may allow it to remove copper from adrenaline and noradrenaline complexes and allow the two catecholamines to resume their antioxidant activities. (J. Phys. Chem. B DOI: 10.1021/acs.jpcb.5b00052; Nancy McGuire)

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The elusive fluorenyl cation is isolated and identified. The 9-fluorenyl cation, a conjugated species with a four π-electron system in its five-membered ring, appears as a typical example of antiaromaticity in many organic chemistry textbooks. There is evidence, however, that shows that the two neighboring benzene groups may be able to compensate for the antiaromaticity. It is difficult to validate this argument without isolating the cation, but preparing it has been elusive until now.

E. Sanchez-Garcia, W. Sander, and colleagues at Ruhr University Bochum and the Max Planck-Institute for Coal Research (Mŭlheim an der Ruhr, both in Germany) generated and isolated the 9-fluorenyl cation (3 in the figure) in an amorphous water ice matrix at very low temperatures. 

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Preparation of the fluorenyl cation

The authors first photolyzed diazofluorene (1) at 365 nm in argon matrices doped with 0.5% water at temperatures between 3 and 10 K. Using ultraviolet–visible (UV–vis) spectroscopy at 25 K, they observed that the triplet signal of the fluorenylidene carbene (2) converts in several minutes to its singlet form via intersystem crossing. They obtained similar results when the photolysis of 1 was carried out in low-density amorphous (LDA) ice at 9 K.

Singlet carbene 2 forms hydrogen bonds with water, which protonates it to form the 9-fluorenyl cation. The UV–vis spectra of 3 isolated in LDA ice matched well with spectra previously obtained with ultrafast absorption spectroscopy. The authors also recorded the infrared spectrum of 3. Its unusual stability is consistent with computational predictions.

The isolation and kinetic stabilization of 3 in a condensed phase shows that LDA ice, a low-polarity, weakly interacting medium, may be used to isolate and study other highly reactive cations that are difficult to observe. (Angew. Chem., Int. Ed. DOI: 10.1002/anie.201411234; Xin Su)

[Although the authors’ introduction discusses the (anti)aromaticity of the 9-fluorenyl cation, they make no mention of it later in the article.—Ed.]

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Computer-aided synthesis design . . . again! H.-J. Federsel, M. G. Hutchings, and coauthors at AstraZeneca (Macclesfield, UK), Chemnotia AB (Södertälje, Sweden), and InfoChem GmbH (Munich) evaluated InfoChem’s retrosynthesis design tool ICSYNTH. The main part of the article describes five case studies in which ICSYNTH was used alongside conventional retrosynthetic analysis and synthetic route design.

The cage hydrocarbon twistane and four key pharmaceutical intermediates required by AstraZeneca were considered. The intermediates include an oxaspiroketone, a pyrimidine-based chiral amine, a furan intramolecular Diels–Alder reaction precursor, and 5-chloropyrazine-2-carboxylic acid.

In all cases, ICSYNTH produced original suggestions that had not been considered by the chemists, but which had some precedents in the literature. In some cases, chemists had to modify the suggestions to avoid potential side reactions. In one case, the suggestion was modified and improved by the chemists. (Org. Process Res. Dev. DOI: 10.1021/op500373e; Will Watson)

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Vary fluorophores’ emission behavior via structural design. Emission colors of inorganic nanoparticles such as semiconductor quantum dots can be manipulated by varying their particle sizes. K. Matsuda and co-workers at Kyoto University (Japan) tuned the fluorescence properties of a series of organic molecules (13 in the figure) by changing the topology of their structures.

Fluorescence of these structures depends on their topology

Fluorophores 1, 2, and 3 have linear, V-shaped, and rectangular topologies, respectively. From 1 to 3, light emission from their solutions increases from weak to strong (fluorescence quantum yields of <0.01. 0.12, and 0.55).

When the solutions are cooled, the emissions intensify to different degrees; from 1 to 3, the intensities vary from great to small. The authors attribute these changes in fluorescence behavior to the structures’ degree of conformational rigidity. (Chem.—Eur. J. DOI: 10.1002/chem.201404745; Ben Zhong Tang)

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