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May 3, 2004 | APPEARED IN VOLUME 82, ISSUE 18

Chlorine catches cagey C50

A fullerene with the elusive C50 cage structure has been prepared in milligram amounts by a group of researchers in China [Science, 304, 699 (2004)]. Smaller fullerenes, such as C50, break the isolated pentagon rule that is thought to contribute to the stability of C60 and C70 fullerenes and larger homologs. Because of its adjacent pentagons and high curvature, C50 is highly labile, and, until now, scientists have been able to study the molecule only in the gas phase. Xiamen University's Su-Yuan Xie, Lan-Sun Zheng, and coworkers modified the graphite arc-discharge process for making C50-containing soot by adding gaseous CCl4 to the reaction mixture in order to trap the reactive fullerene as C50Cl10 (shown, chlorine atoms in green). Xie and Zheng 's group isolated and characterized 2 mg of C50Cl10 and found that chlorination occurred at the molecule's most reactive sites--the pentagon-pentagon junctions.


DNA computer diagnoses

A "molecular computer" made of DNA can diagnose disease and dispense drug molecules, Israeli scientists report. The molecular computer described by Ehud Shapiro, a professor in the departments of computer science and applied mathematics and of biological chemistry, and his coworkers at the Weizmann Institute of Science, Rehovot, Israel, measures the levels of messenger RNA indicator molecules to diagnose cancer in an in vitro synthetic system and responds by releasing an antisense DNA drug with anticancer properties [Nature, published online April 28,]. To make the diagnosis, the computer sequentially determines whether particular indicator molecules are present. If the computation ends up in the positive state, the drug molecule is released. A negative result in the computation results in the release of a drug suppressor, also a single-stranded DNA molecule. The drug and drug suppressor are contained in single-stranded loops and are protected by double-stranded stems from interacting with one another or the target mRNA. They are cleaved off and released depending on the results of the calculations. The team demonstrated the technique using simplified synthetic models of genes from prostate cancer and small-cell lung cancer.


'Chicken feet' run hydrogenations

Credit: SCIENCE © 2004
Credit: SCIENCE © 2004

A team at Pfizer Global R&D, Ann Arbor, has designed and tested the ligand shown for asymmetric rhodium-catalyzed hydrogenation. Most chiral phosphine ligands for the same purpose are C2 symmetrical. The new ligand, dubbed trichickenfootphos, has C1 symmetry. Garrett Hoge and coworkers have used the rhodium complex of the ligand to prepare tert-butylammonium (S)-3-cyano-5-methylhexanoate from tert-butylammonium 3-cyano-5-methylhex-3-enoate at the 100-g scale [J. Am. Chem. Soc., 126, 5966 (2004)]. The chiral compound is a key intermediate in the route to pregabalin, a drug candidate for treating anxiety and epilepsy that is being reviewed for approval by FDA. For this application, the new ligand forms a catalyst that is superior in enantioselectivity and catalyst loading to the previous best, which uses Me-DuPhos, a ligand that is now proprietary to Dow Chemical. Hoge says that the ligand is relatively easy to prepare and handle and that the reaction should be readily scalable. Pharmaceutical industry watchers say that, if approved, pregabalin could realize annual sales of up to $1 billion.


Discerning chiral-catalyst selectivity

Screening chiral catalysts based on catalytic intermediates avoids the pitfalls of methods based on product analysis. Enantiomeric ratios of products do not truly reflect catalyst selectivity because of interference from background reactions or catalyst impurities. A better picture can be gleaned from directly monitoring positively charged catalyst-reactant complexes by electrospray ionization mass spectrometry. Christian Markert and Andreas Pfaltz at the University of Basel, in Switzerland, demonstrate the concept with palladium-catalyzed kinetic resolution of allylic esters [Angew. Chem. Int. Ed., 43, 2498 (2004)]. With use of a 1:1 mixture of pseudoenantiomeric substrates (enantiomers labeled with substituents of different masses), the catalyst-reactant complexes formed from the pseudoenantiomers can be observed as separate peaks in the mass spectrum. Relative selectivities of catalysts then are established from the ratios of peak heights. Markert and Pfaltz further show that simultaneous screening of multiple catalysts in the same homogeneous solution is possible. The method also will work with reactions of meso compounds but cannot be applied directly to asymmetric transformations of prochiral substrates.


RNA's H-bonds are stronger than DNA's

The strengths of the hydrogen bonds that hold pairs of nucleotide bases together in RNA and DNA have always been assumed to be roughly equivalent. But in fact, RNA's hydrogen bonds are stronger than DNA's, according to a new study by assistant professor Andy C. LiWang and graduate student Ioannis Vakonakis of Texas A&M University's department of biochemistry and biophysics [J. Am. Chem. Soc., published online April 21,]. The pair first substituted a deuterium for the imino hydrogen (red) of uridine in an adenine-uridine base pair (shown) in a RNA duplex. They probed the effect that this deuterium substitution has on the NMR chemical shift of the starred carbon atom in the adenine, then compared it to the isotope effect observed in an adenine-thymine base pair in a homologous DNA duplex. Despite the structural similarity between RNA and DNA, the isotope effect--which can be used to quantitatively gauge the relative strength of hydrogen bonds--is significantly larger in RNA, LiWang says. His lab is now using nucleotide analogs and computational methods to figure out why.



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