Noteworthy Chemistry

April 1, 2013

How does alkyl chain length affect the luminescence behavior of fluorogen aggregates? Understanding structure–property relationships is important because this information can be used to guide the molecular design of new materials with desirable properties. W. Yang and co-workers at Qingdao University of Science & Technology (China) synthesized a series of 9,10-bis[(9,9-dialkyl-2-fluorenyl)vinyl]anthracene fluorogens (13) and investigated the effect of alkyl chain length (n) on the light-emitting behavior of their aggregates.

The emission color of the fluorogen in the solid state is blue-shifted as the alkyl chain is lengthened. The aggregates of 1, 2, and 3 emit yellow, yellowish-green, and green light, respectively. Pressing or grinding the aggregates causes their emissions to red-shift as a result of the mechanically induced crystalline-to-amorphous phase transition. Fluorogens with longer alkyl chains exhibit greater color changes (i.e., larger mechanochromic effects).

The color change can be reversed by annealing or fuming. The emission color of ground aggregates of 3 recovers spontaneously because its long alkyl chains lower its cold-crystallization temperature to below room temperature. (J. Mater. Chem. C 2013, 1, 2028–2035; Ben Zhong Tang)

Light irradiation unleashes copper to kill cancer cells. Copper is an important bioactive element, but it requires delicate regulation. Its bioactivity depends on its coordination environment. Well-designed copper complexes can be used to modulate copper-sensitive biological activity.

K. J. Franz and coauthors at Duke University (Durham, NC), the University of Pune (India), and Howard University (Washington, DC) designed a Cu(II) “cage” that releases Cu(II) upon photoirradiation to induce nonapoptotic cancer cell death.

Ligand 1 is a tetra-coordinating chelator with a photolabile nitrophenyl group. Its copper complex (2) can be photocleaved to release Cu(II) along with fragments 3 and 4.

Complex 2 is stable under simulated physiological conditions even in the presence of strong reducing agents. It is only slightly cytotoxic to MCF-7, HeLa, and HL-60 human cancer cells below the concentration of 100 μM.

When 2 is irradiated with 350-nm UV light for 90 s, the viability of all three types of cancer cells becomes negligible within 24 h. Cytoplasmic vacuolization indicates that the cell deaths occur through a nonapoptotic pathway.

The cytotoxicity of 2 can be enhanced by adding a nontoxic dose of H2O2. This procedure lowers the IC50 of UV-irradiated 2 from 75 to 30 μM. (Chem. Commun. 2013, 49, 2460–2462; Xin Su)

Tweak a classical alcohol chlorination reaction to retain configuration. Alcohols are typically chlorinated by heating them to reflux in neat SOCl2. With chiral alcohol substrates, however, the harsh reaction conditions often produce racemic chlorides. L. Bellucci, S. D. Lepore, and coauthors at Florida Atlantic University (Boca Raton), the CNR Institute of Nanoscience (Modena, Italy), and IBM Zurich Research Laboratory developed a mild chlorination of cyclic alcohols that uses TiCl4 as an additive to SOCl2.

The researchers treated their model substrate,L-(–)-menthol, with 1.5 equiv SOCl2 in CH2Cl2 at 0 °C for 1 h to form a chlorosulfite, which they then subjected to 0.1 equiv TiCl4 at 0 °C for 15 min. The yield of the chlorinated product is 91%–93% with complete retention of configuration.

The authors expanded their method to other cyclic alcohols such as 1-admantanol and cholestanol. When the substrates are cis- and trans-3- and 4-methylcyclohexanols, a hydride-shift side reaction occurs, and in some cases the products are cis–trans mixtures of 3- and 4-methylcycloxexyl chlorides. In only one case, the chlorination of cis-3-methylcyclohexanol at –78 °C, does the reaction proceed with complete retention.

The authors used density functional theory to develop a proposed mechanism (see figure). After the chlorosulfite forms, it complexes with TiCl4 at the sulfoxide oxygen atom. The nonplanar carbocation is stabilized by hyperconjugation. Chloride attacks from the front side to complete the reaction.

Preliminary data show that the method can be extended to bromination reactions with the reagents SOBr2 and TiBr4. (J. Org. Chem. 2013, 78, 2118–2127; José C. Barros)

Make a photoresponsive silk–elastin copolymer. Biocompatible silk–elastin-like protein polymers (SELPs) have potential applications in drug delivery and tissue engineering. D. L. Kaplan and co-workers at Tufts University (Medford, MA) incorporated biocompatible retinal (a form of vitamin A) as a photoactive element in SELPs. They added a lysine unit to the sequence to form a new ≈45-kDa SELP that they call PS2E8K. PS2E8K has a 2.8:1 silk/elastin ratio and exhibits several conformational states.

The authors used the Schiff base reaction to incorporate retinal into the PS2E8K copolymer. The retinal-modified SELP has less β-sheet structure and more random-coil conformations than unmodified PS2E8K.

Optical polarization was used to induce an anisotropic response in the modified PS2E8K that is caused by trans–cis isomerization of the retinal component. The complicated isomerization profile of retinal (e.g., multiple cis states) creates future pathways for investigating the relationship of structure, optical behavior, and responsiveness. (J. Am. Chem. Soc. 2013, 135, 3675–3679; LaShanda Korley)

Protect anthracene-based fluorophores with “straps”. 9, 10-Diphenylanthracene (DPA), like its parent compound anthracene, is strongly fluorescent and widely studied for use in optoelectronics and organic semiconductors. Anthracene-based fluorophores, however, often are photochemically damaged in solution and subject to aggregation-induced self-quenching.

K. Kobayashi and colleagues at Shizuoka University, Hamamatsu Photonics, and Bruker AXS (Yokohama, all in Japan) developed a protecting strategy that uses alkylene “straps” to shield the anthracene core from photochemical reactions and aggregation.

The authors converted anthraquinone to tetramethoxy compound 1 in two steps in 93% yield. After demethylation of 1 with BBr3 followed by hydrolysis, tetraol 2 was treated with 1,n-dibromoalkanes to give the corresponding doubly-strapped diphenylanthracenes (3a3b) in moderate yields (26%−66%).

The electronic transitions of compounds 3a3c are similar to those of DPA, although the HOMO and LUMO energies increase. These compounds, especially 3b, exhibit excellent photostability compared with DPA. Sterically protected tetrakis(silyl ether) 4 is similarly stable. Under irradiation with an 18-W fluorescent light bulb in air, the 1H NMR spectrum of 3c changed little in ≥10 days, whereas DPA was completely consumed by photoreactions within 2 days.

In the solid state (cast films, powders, and crystals), the quantum yields of the strapped fluorophores increase in the order 3c < 3a < 3b. The authors attribute this sequence to the length of the straps: In 3a and 3c, the straps (C6 and C8) are too short or too long, leading to a higher probability of nonemissive deactivation pathways. (J. Org. Chem. 2013, 78, 2206–2212; Xin Su)

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