SCIENCE & TECHNOLOGY CONCENTRATES
It’s one of those quirks of the periodic table: Molecular oxygen, O2, is stable, ubiquitous in Earth’s atmosphere, and often used as an oxidant in chemical reactions. But sulfur monoxide, SO, just one element removed, is unstable and has a fleeting existence. Chemists have long been searching for ways to stabilize SO to make it useful as a small molecule for organic synthesis, such as complexing it with transition metals, but to little avail. Douglas W. Stephan, Lauren E. Longobardi, and Vanessa Wolter at the University of Toronto have now used frustrated Lewis pairs to tame SO (Angew. + – R2P B(C6F5)2 Chem. Int. Ed. 2014, DOI: 10.1002/anie.201409969). N O S Frustrated Lewis pairs are R´ acid-base pairs dressed R = mesityl, R´= p-tolyl with bulky substituents that prevent them from coming close enough together to completely form a neutral adduct. The resulting reactive species can function like a metal catalyst to activate small molecules such as H2, CO2, CO, and N2O. The Toronto chemists show that the combination of a bulky phosphine and bulky borane can capture N-sulfinylamines to form an unusual seven-membered heterocycle containing six different elements, including an SO unit (shown). In a set of test reactions, the researchers used the new chemical to transfer SO to a phosphine, rhodium complex, or N-heterocyclic carbene, a first step in using SO as a reagent.—SR
SHU TTERSTOCK
SNIFFING OUT ANXIETY IN RATTLED RATS Plenty of critters use chemicals to communicate. These chemicals, O known as pheromones, can signal everything from raising Hexanal an alarm to a readiness for romance. Now, for the first time, scientists have identified pheromones in rats (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/ pnas.1414710112). By Stressed-out rats produce aldehydes that make other rats anxious.
MODIFIED BASE LOOSENS UP DNA Researchers have discovered how a modified DNA base may regulate cellular function. 5-Formylcytosine (5fC), a modified cytosine, is believed to help control demethylation and gene expression, but how it functions has been unknown. NH2 Shankar BalasuN bramanian and coworkers at N O the University of Cambridge now Cytosine find that 5fC’s presence causes localized conforNH2 O mational changH N es in duplex DNA (Nat. Struct. O N Mol. Biol. 2014, DOI: 10.1038/ 5-Formylcytosine nsmb.2936). DNA sequences with conventional bases adopt the classic Their X-ray struc- double-helical conformation (top), whereas the modified base ture of double5-formylcytosine causes the helix to bulge and loosen (bottom). This conformation, called F-DNA, may help control gene expression. stranded DNA containing a 5fC cluster shows that it adopts a unique conformation, which they call F-DNA. This bulge is wound less tightly than normal DNA, which might ease intervention by a demethylation enzyme or transcription factors. But chemical biologist Chuan He of the University of Chicago comments that “the formation of clusters of 5fC and potential impacts on DNA conformation in vivo still need to be further studied and confirmed.”—SB NAT. STRUCT. MOL. BIOL.
LEWIS PAIR GETS A HANDLE JUST SO ON SULFUR MONOXIDE
studying the chemicals produced by rats when they are stressed-out, Japanese researchers identified two key compounds: 4-methylpentanal and hexanal. The team, led by the University of Tokyo’s Yukari Takeuchi, found that exposing rats to these two chemicals in combination prompted the rodents to display increasingly anxious behavior. Neither aldehyde increased anxiety on its own, the researchers note—they had to be present in a mixture. Hexanal is a common alarm H O pheromone produced by many insects, H such as weaver ants and leaf-footed bugs, 4-Methylpentanal but little is known about 4-methylpentanal, the researchers say. It’s possible, they reason, that 4-methylpentanal transmits species-specific information whereas hexanal indicates the accuracy of that information. The finding, they add, enhances our understanding of chemical communication in mammals.—BH CEN.ACS.ORG
12
DECEMBER 22, 2014
ELECTRIC FIELD SPEEDS UP ENZYME REACTIONS Electrostatic fields in enzymes play a leading role not just in getting substrates to bind, but in the rate of the catalytic process itself, report Stephen D. Fried, Sayan Bagchi, and Steven G. Boxer of Stanford University (Science 2014, DOI: 10.1126/science.1259802). Whether or how such electric fields directly influence reactions has been controversial. Fried, Bagchi, and Boxer studied ketosteroid isomerase, which participates in steroid biosynthesis and degradation by relocating a C=C bond. The enzyme has one of the highest known unimolecular rate constants in biochemistry. The researchers used vibrational Stark effect spectroscopy to measure changes in an inhibitor’s vibrational energy levels induced by the enzyme’s electric field. They found that the enzyme exerts a strong electric field on a key C=O group involved in the enzyme’s rate-determining step and that the magnitude of the field correlates with the catalytic rate enhancement. The team
A
SCIENCE & TECHNOLOGY CONCENTRATES O Tyr
O Tyr OH
•••
•••
OH
Asp
CO2H
O
•••
•••
O
H H –
O
O
Asp
CO2H
O
Asp
In ketosteroid isomerase, the electric field induced by tyrosine and aspartic acid residues on a C=O group helps to speed up isomerization of substrates.
estimates that about 70% of the enzyme’s ability to speed up isomerization ultimately comes from the electric field effect, whereas the remainder comes from positioning a basic protein residue to abstract a substrate proton. “The electric field could be a useful design criterion in the ongoing efforts to engineer enzymes with unnatural or enhanced functions,” the researchers write.—JK
O sine
SCIENC E
ROCK ON, PROTEIN DESIGNERS Richard P. Feynman, the often-quoted physicist, once wrote: “What I cannot create, I do not understand.” Researchers putting that maxim into practice are now a step closer to understanding membrane-spanning ion-transporter proteins: They’ve created a simple version from scratch (Science 2014, DOI: 10.1126/science.1261172). Scientists have designed numerous proteins to bind metal ions or catalyze simple reactions in the name of understanding protein folding and function. Designing an ion transporter is more difficult because the design must account for multiple stable protein conformations that interconvert. William F. DeGrado took on the challenge with fellow University of California, San Francisco, researcher Michael Grabe, MIT’s Mei Hong, Dartmouth College’s Gevorg Grigoryan, and others. Their designed transporter, called Rocker, contains two interacting pairs of helices that rock between two forms—one
To design an ion-transporter protein, chemists had to consider how a protein might alternate between conformations that facilitate movement of zinc ions (red balls).
open to the inside of a membrane, the other to the outside. H H Biophysical tests show the transO– porter shuttles zinc and cobalt ions, but not calcium ions, across a Asp membrane. Rocker’s activity falls short of natural proteins. But that’s a minor point to Gaetano T. Montelione of Rutgers University, who comments that considering protein dynamics “is an important innovation, essential for creating a functional iontransporting membrane protein.”—CD
RECEPTOR TRIGGERS PSEUDOALLERGIC RESPONSE TO DRUGS
in the martian atmosphere (Science 2014, DOI: 10.1126/science.1261713). Organic compounds, particularly methane, are generally produced by living organisms, although these compounds can be synthesized by abiotic reactions of soil, water, and solar radiation. Right now, scientists say they have no way of determining their source on Mars. But the rover did detect the presence of chlorobenzene, dichloroethane, dichloropropane, and dichlorobutane. The molecules are likely the products of precursor organics and formed during heating of the perchlorate-rich martian soil. Methane plumes have been detected on Mars previously, but the new measurements are the first from a craft on the martian surface. Over a period of 20 months, Curiosity recorded background atmospheric levels of methane of about 0.7 ppb. But then suddenly methane levels climbed to 9 ppb over several months. Scientists suggest the gas is periodically escaping from clathrates beneath the ground.—EKW
Mast cells—the immune cells involved in allergic reactions—are usually activated by antibodies. But mast cells can also respond to cationic substances, including drugs, in what are called pseudoallergic reactions. A team of researchers led by Xinzhong Dong of Johns Hopkins University School of Medicine has identified the receptor MICROSCOPIC INSIGHTS protein on mast cells that’s responsible for these pseudoallergic drug reactions (Nature INTO ROMAN MORTAR 2014, DOI: 10.1038/nature14022). In mice, a receptor called Mrgprb2 is responsible for The ancient Roman office and shopping histamine release, inflammation, and airway complex known as Trajan’s Markets is a contraction. The team noted that mutant monument to resilient architecture. More mice without the receptor had none of these than 1,900 years old, this structure has withresponses. The mouse receptor is an analog stood moderate earthquakes and floods. of the human receptor MRGPRX2. The reOne secret to its staying power, scientists searchers discovered that many small-molsay, is the mechanical resilience of the ecule drugs conmortar that binds together cobbletaining a tetrahysized pieces of brick and porous rock N droisoquinoline that make up the market buildings. O unit target the Researchers led by Marie D. Jackson receptor. Drugs of the University of California, BerkeTetrahydroisoquinoline motif with this motif ley, used computed tomography and include neuromuscular blocking drugs and synchrotron X-ray microdiffraction to study the fluoroquinolone class of antibiotics. a reproduction of the Roman mortar as it Dong and coworkers suggest the new inforcured (Proc. Natl. Acad. Sci. USA 2014, DOI: mation can be used during drug discovery to 10.1073/pnas.1417456111). Over the course screen out compounds that are likely to trigof 180 days, the mortar made from a simple ger pseudoallergic reactions.—CHA recipe of hydrated lime and volcanic ash developed platelike crystals of strätlingite, a durable calcium-aluminosilicate mineral. CURIOSITY CONFIRMS These mineral plates provide reinforcement and prevent cracks from propagating ORGANICS ON MARS through the mortar. The researchers obNASA’s Mars rover Curiosity has discovered served these same plates of strätlingite in that organic compounds are present in the samples of the mortar taken from Trajan’s soil of the Red Planet, scientists announced Markets. The Roman mortar suggests routes on Dec. 16 at the American Geophysical to making sturdy concrete via a process that Union meeting in San Francisco. Curiosity releases less carbon dioxide than the stanalso recently detected a localized but dradard process for making modern Portland matic surge of methane of unknown origin cement.—BH CEN.ACS.ORG
13
DECEMBER 22, 2014
