HOW ASPIRIN REDUCES COLON CANCER RISK
EARTHWORM’S GLOW UNEARTHED
A variety of studies have suggested that taking aspirin can decrease the risk of colon cancer. But the mechanism by which the common painkiller exerts its protective effect has eluded researchers. A team led by Andrew T. Chan of Massachusetts General Hospital and Sanford D. Markowitz of Case Western Reserve University now reports that aspirin’s colon cancer protection is linked to levels of an enzyme called 15PGDH (Sci. Transl. Med. 2014, DOI: 10.1126/ scitranslmed.3008481). The researchers note that the enzyme plays a role in the degradation of prostaglandins, which are important lipid messenger molecules that can also be involved in O OH certain colon cancers. Aspirin appears to reduce O prostaglandin levels by O inhibiting the activity of another enzyme involved Aspirin in prostaglandin synthesis. The researchers examined tissue samples from 270 cases of colon cancer stemming from two studies that tracked aspirin use of 128,000 people for three decades. They found that people who consumed at least two 325-mg aspirin tablets per week lowered their risk of colon cancer by 50%— but only if their 15-PGDH levels were higher than average. The finding could help identify people who can reduce their colon cancer risk with aspirin. Likewise, identifying individuals who won’t benefit from aspirin’s protection could help them avoid the drug’s side effects, which include gastrointestinal bleeding and ulcers.—SE
In the forest soils of Siberia, there is a tiny worm that will emit blue light if given a little tickle. The critter, known scientifically as Fridericia heliota, gets its glow via the oxidation of a previously unknown O HO luciferin compound facilitated by a luciferase enOH zyme. This is the same mechanism that many N H bioluminescent creatures, including fireflies and O certain jellyfish, use to produce so-called cold CH3O light. To date, only a handful of luciferin analogs have been chemically charO O HN acterized. Researchers led by O HO Ilia V. Yampolsky of the RusN H sian Academy of Sciences’ InHO O stitute of Bioorganic Chemistry wanted to know precisely which chemical made F. heliota glow. The team collected approximately 60,000 of the little worms, each of which is only about 15 mm long, and This Siberian earthworm then extracted their bioluminescent components (Anglows blue when gew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201400529). mechanically The researchers were able to isolate only 0.005 mg of the stimulated, thanks to its unique luciferin. color-giving chemical from which they could do limited NMR and mass spectral analyses. Using these studies, they narrowed down the structural possibilities to four isomeric peptides and then synthesized them. One of the synthesized compounds (shown) turned out to be a match with the natural Siberian worm luciferin and produced light when mixed with crude Fridericia luciferase.—BH
DIAZOALKANE EXPANDS FLUORINE FOCUS ON ETHYL GROUPS
are relatively scarce. The approaches tend to be direct additions of perfluoroalkyl groups using organometallic transfer reagents and don’t use perfluoroalkyl-containing building blocks. Pavel K. Mykhailiuk of Enamine, a global supplier of research chemicals based in Kiev, Ukraine, has now developed a new building block for introducing C2F5 into organic molecules (Chem. Eur. J. 2014, DOI: 10.1002/chem.201304840). Mykhailiuk safely generates the fluorinated diazoalkane, C2F5CH=N2, in situ from C2F5CH2NH2•HCl and NaNO2. He demonstrated the utility of the reagent by using it in [3 + 2] cycloadditions with alkenes to prepare perfluoroethylated O
Developing new methods for introducing fluorine into complex organic molecules O C2F5 has been all the N Ph N Ph rage during the C2F5 C2F5 NaNO2 O past few years. N N NH2•HCl N2 Researchers O H preparing drug Diazofluoroalkane Pyrazoline Ph = phenyl candidates and crop protection chemicals typically seek to pyrazolines (one example shown) with betadd a single fluorine atom or trifluoromethter than 95% conversion rates. Mykhailiuk yl group and now have myriad ways to do so. believes the diazofluoroalkane will also But methods for adding longer, more lipobe as useful as other diazoalkanes for cyphilic perfluoroalkyl groups such as pentaclopropanations, carbene insertions, and fluoroethyl, –C2F5, to complex molecules alkyne cycloadditions.—SR CEN.ACS.ORG
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APRIL 28, 2014
SOLID CONTRAST AGENT ENABLES LONG-TERM MRI An injectable contrast agent for magnetic resonance imaging that coalesces into a solid now enables long-term monitoring of oxygen levels in tissues without the need for an invasive procedure, which is required to implant standard oxygen electrodes or a solid MRI contrast agent (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/pnas.1400015111). The new material maintains the concentration of the contrast agent in the tissue of interest for extended periods of time, permitting repeated quantitative measurements. Michael J. Cima and coworkers at Massachusetts Institute of Technology make the sensors from a saline suspension of oxygen-responsive dodecamethylpentasiloxane embedded in a support matrix of polydimethylsiloxane (PDMS). In rats, the injected PDMS particles coalesced into a solid sensor “depot” in muscle tissue, and there were no signs of an adverse tissue reaction. By using the right combination of MRI pulse sequences, the signal from PDMS is eliminated and the oxygen-responsive signal is preserved. The researchers used the sensors to measure partial pressure of oxy-
ANGEW. CHEM. INT. ED.
SCIENCE & TECHNOLOGY CONCENTRATES
SCIENCE & TECHNOLOGY CONCENTRATES
SQUEEZING MORE OUT OF CORN LEFTOVERS There’s a lot more to corn than the sugar used as a sweetener and to make ethanol. A characterization study on one of the byproducts of corn processing, a condensed liquid known as defatted corn syrup (DCS), suggests that it has been O overlooked as a potential NaO S valuable source of biobased O chemicals (ACS Sustainable Chem. Eng. 2014, DOI: 10.1021/ sc400508p). When corn is milled and processed, a major part of the starting material is drawn off to ferment into ethanol. Most of the leftover solids, called dried distillers grains, are repurposed as animal feed. David R. Shonnard and coworkers at Michigan Technological University decided to take a closer look at DCS, which is often added to the dried distillers grains, by carrying out a detailed compositional analysis. The researchers found that the waste liquid is rich in fiber, carbohydrates, protein, and more. They then calculated the potential yields of various chemicals that could be made via fermentation processes using the roughly 700,000 metric tons of the material produced annually in the U.S. Although DCS doesn’t appear useful for making fuels, it could be used to meet current U.S. demand for succinic acid (about 25,000 metric tons) or global demand for histidine (360 metric tons). Biobased chemical manufacturer Working Bugs, which was involved in the study, is considering options for capitalizing on the findings.—SR
INFRARED SPECTROSCOPY GETS A RESONANCE RAMAN ANALOG In resonance Raman spectroscopy, matching the excitation frequency to an absorption frequency in the sample boosts the re-
N
sulting Raman signal. But not all molecular vibrational modes are Raman active, and there has been no infrared version of resonance Raman. John C. Wright and coworkers at the University of Wisconsin, Madison, now report that a spectroscopic technique called triply resonant sum frequency (TRSF) spectroscopy provides that missing IR analog (J. Phys. Chem. A 2014, DOI: 10.1021/jp5018554). In TRSF spectroscopy, excitation pulses from three lasers interact with sample molecules to generate signals involving two vibrational states and an electronic state. When the laser pulses are in resonance with those coupled vibrational and electronic states, the signal from IR-active vibrational modes is enhanced. Wright and coworkers demonstrated the method ONa with copper phthalocyanine tetrasulfonate in O S O deuterated water. The symmetry of the copper N complex means that its N N vibrational modes are either N Cu Raman active or IR active, but N
N
N O S O
O S
ONa
ONa
O
This region of the resonance IR spectrum of a copper complex (shown) differs from both the resonance Raman and the FTIR spectra.
not both. The researchers observed features in the resonance IR spectrum that were not observable in either the FTIR spectrum or the resonance Raman spectrum, making the technique potentially useful for studying biomolecules such as hemes, as well as synthetic transition-metal complexes.—CHA
NEW ORGANIC DESIGNS FOR FERROELECTRICS Using a newly developed computational technique to predict structural and electronic properties of as-yet-unsynthesized materials, chemists have designed a group of ferroelectric organic crystals that promise to outperform current state-ofCEN.ACS.ORG
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the-art materials (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja5017393). Ferroelectric materials have a knack for flipping electrical polarization when triggered by an electric field. That property makes them useful in random access memory devices, capacitors, and transistors. Common ferroelectrics such as barium titanate are inorganic. Because the range of applications could be broadened by lighter, more flexible, and less expensive materials, scientists have been searching for organic versions. Motivated by a 2012 study reporting success in synthesizing ferroelectrics based on tetrathiafulvalene (TTF), an electron donor, and pyromellitic diimide (PMDI), an electron acceptor, Shuang Chen and Xiao Cheng Zeng of the University of Nebraska, Lincoln, computationally screened tens of thousands of crystal structures based on TTF and PMDI motifs. The search turned up three highly stable compounds with predicted polarization values up to twice as large as today’s top performers.—MJ J. PHYS. CHEM. A
gen in the tissue of the rats as they breathed gas streams containing different amounts of oxygen or as they experienced restricted blood flow to a limb. The sensors remained functional for at least a month after injection. By using different contrast agents and support materials, the same strategy could be used to make sensors optimized for other analytes, the researchers suggest.—CHA
APRIL 28, 2014
ZIPPING UP WOUNDS WITH NANOPARTICLES Aqueous solutions of nanoparticles could one day replace sutures for healing cuts in skin and for certain surgical procedures, such as liver surgery, where stitches can be traumatic to soft tissues. Using aqueous solutions of silica or iron oxide nanoparticles, researchers in France led by Didier Letourneur of INSERM Paris and Ludwik Leibler of CNRS-ESPCI ParisTech found they were able to control bleeding and heal deep wounds in the skin and livers of rats (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/ anie.201401043). The wound closure occurs through a process known as nanobridging, wherein the nanoparticles adsorb to the tissue and biomacromolecules attach to the nanoparticles, ensuring that the wound surfaces adhere to one another. In addition to wound healing, the researchers used the nanoparticle solutions to fix medical devices and tissue-engineering constructs to organs, such as a rat’s beating heart. They note that for skin and liver treatment, the procedure is fairly simple: Just dab the solution on the wound, push the wound edges into contact, and watch the wound seal in a matter of minutes. “Translation to clinical practice will require careful safety and toxicity investigations,” the team notes.—BH
