science/technology dustry," Taylor says. 'The industry was experiencing problems with the measurement of noble metals in car exhaust catalysts. This is a real international cross-border issue involving the people who supply the metals, the people who produce the catalytic converters, the people who do the recycling, and the contract laboratories who carry out the measurements for these parties." Most results for all four metals measured were within the band from 20% above to 20% below the certified range midpoint. And, as with other rounds, there was little difference in the spreads of results between self-declared accredited laboratories and selfdeclared nonaccredited laboratories.
As usual, a few results were way off scale. For example, one accredited laboratory reported a result about 1,000 times higher than the certified value for platinum. The largest variability in results has occurred in the three rounds that focused on the determination of trace elements in water. The spreads of results in IMEP-9 were generally very similar to those for IMEP-3, published in 1996, and IMEP-6 results published last year. In all three water rounds, about 90% of the laboratories reported values within 50% of the certified midpoint value but relatively few within the certified range. In a few cases, the reported values deviated from the
The Beat Goes On Rhythmic stereochemical inversion observed in supramolecular system
T
he chirality of a supramolecular system that incorporates rigid oligomers flip-flops rhythmically as a chiral ligand is added. This novel phenomenon was discovered by the group of Stefan Matile, assistant professor of chemistry at Georgetown University, Washington, D.C. The behavior is unusual because it is due to ligand-receptor binding only. "Normally, you have to break and reassemble chemical bonds to flip one enantiomer to the other," says Matile, who by June will have moved to the University of Geneva, Switzerland, as an associate professor of chemistry. "In this case, just adding something flips the whole apparent stereochemistry." The complex system displaying this unique property consists of stiff oligomers embedded in a bilayer composed of egg yolk phosphatidylcholine. The oligomer spans the length of the bilayer and terminates in a ligandbinding group. This group, an iminodiacetate, sits on one surface of the bilayer, alongside the phosphatidylcholine "heads." When added, copper ions bind to the iminodiacetate, forming a Cu (II)-receptor complex. Titration of this complex with L-histi32
MAY 31, 1999 C&EN
dine—but not the opposite enantiomer— produces rhythmic stereochemical inversion, as revealed by circular dichroism (CD) spectra [Enantiomer, 4, 127 and 139(1999)]. The work is "pioneering," says Nina
certified value by several hundred percent. The results indicate a general need to improve the reliability and comparability of chemical measurements, particularly for trace elements in water, and for further rounds of evaluation using certified test samples. "The IMEP rounds that have been completed so far have been very well received," Moody says. "The only criticism is that there has not been enough of them." Further IMEP rounds under consideration include lead in wine; 1 0 B/ n B isotope ratios in water; boron in biological matrices; cadmium in rice; sulfur in oil; and cadmium, mercury, and iodine in urine.^ Berova, senior research scientist at Columbia University and an expert in the use of CD spectroscopy for structural determination. She and Matile collaborated on structural studies of natural products when he was a postdoctoral researcher in the lab of Columbia chemistry professor Koji Nakanishi, and she has followed Matile's work closely. "Chiroptical rhythmicity, as Matile calls the behavior, is really a new phenomenon," Berova says. It surely will stimulate the use of CD spectroscopy to reveal molecular chirality, especially at the supramolecular level, she adds. Matile does not understand exactly what is happening. He thinks that formation of tight ion pairs between the ligand-receptor complex and the membrane surface triggers events that lead to the peculiar stereochemical rhythms. At the pH used in the experiments, histidine and choline both exist as zwitterions. Matile has evidence that they form two ion pairs, and he speculates that succeeding events hinge on the stereochemistry of the oligomer and the bilayer. The oligomer is a rigid-rod septi(/>-phenylene). Rigid-rod molecules have minimal flexibility, because few of their bonds can rotate freely. 'Their molar entropy is very low," Matile says. 'They make very nice Clockwise from top left: Matile, Tedesco, Ghebremariam, and Sakai
that the results are real, Matile building blocks for higher or says. dered structures." Chiral rhythms The peculiar phenomenon is Six of the seven benzene rings only the latest outcome of Matile's in the oligomer are substituted engagement with rigid-rod mole with methyl or ethoxy groups at cules based on oligophenylenes. positions ortho or meta to the In addition to oligomers that mod bond connecting adjacent ben el potassium channels, he has pro zenes. The substitution creates duced molecules that facilitate ion five chiral axes, and the rotations transport across bilayers, act as around these axes make the ste membrane-spanning proton wires, reochemistry 'Very confusing," and form barrels with ionophoric Matile says. But the population of oligomers in the bilayer should properties. be enriched in the most stable The focus on asymmetric rigidpair of enantiomers, he says. rod scaffolds is part of a wild idea to create a synthetic amoeba— Matile thinks L-histidine ste that is, a supramolecular structure reoselective^ induces aggrega that can engulf an object outside of tion of one enantiomer, causing an it by folding a membrane and cre excess in unaggregated units of ating a small vesicle to incorporate the mirror image. As more ligands the "extracellular" foreign object. are added, "sooner or later you reach a critical value, and the ag "What we want to do—mimicking gregation shifts," yielding an ex receptor-mediated endocytosis— cess of the other enantiomer, he is something that nobody believes explains. Flip-flopping of absorp can be done," Matile says. tion peaks in the CD spectra re Matile thought he could do it flects the back-and-forth shifting. with oligophenylenes with a ligand-binding site on one end and That only L-histidine induces bulky groups at the opposite end. the rhythmic behavior of this par ticular system also is notable, The idea was that when such rigid Berova says. Whereas chiral sur rods are embedded into a bilayer, faces are well recognized in en the inner layer, where the bulky abling chromatographic resolu substituents would be, will expand. tions of racemic mixtures, the The increase in volume would cre importance of the chirality of bioate a curvature that would envelop membranes for biological activity the ligand-binding site. 10 15 20 25 is not well understood. Progress in "So far the idea hasn't worked," Ligand concentration, μΜ understanding enantiodiscriminaMatile says. "When we make the tion by biomembranes is expected substituents more bulky, they Rhythmic stereochemical inversion of the su to come from multidisciplinary pramolecular system shown at the top is reflect don't go into the membrane any ed in theflip-floppingof peaks in the circular studies at the interface of chemis more but form vesicles and mi dichroism (CD) spectrum (bottom). Formation try and biology, such as those be celles by themselves instead." of tight ion pairs between zwitterions in the ing done by Matile, she adds. For now, Matile hopes that the phosphatidylcholine of the lipid bilayer (gray) Because D-histidine, the mir system displaying chiral rhythmic and those in L-histidine (red) induce stereose ror-image of the chiral inducer Lity "can be used to do more inter lective aggregation of therigid-rodoligomer (en histidine, is totally inactive, the esting things." What he dreams of closed in green). L-Histidine is bound to the olig omer through copper(II) in the iminodiacetate Georgetown work suggests that is a chiral clock, with chirality flipreceptor of the oligomer (enclosed in purple). bilayer membranes can act as flopping with time. When asked stereoselective chiral transduc what such a clock would do, he ers. Thus, D-histidine would in blurts out, "I don't care." The fasci duce the rhythmicity only in the pres channels [Angew. Chem. Int. Ed., 3 8 , nation, he explains, lies in how such a ence of the mirror image of the bilayer. 540(1999)]. clock would reflect life. The rhythmic chiral inversion of the To prove that the multivalence of "Biology is rhythmical," he says. supramolecular system was totally un polyhistidine is required for potassium "For example, why we go to sleep and expected, says Matile. He and gradu transport, Matile and Ghebremariam then wake up is explained in part by a ate student Bereket Ghebremariam tried the experiment with the univalent receptor in the brain that is shut down were experimenting with it as a nega L-histidine. "That's when Bereket by a ligand at night and turned on by the tive control of a similar system in which brought these strange CD curves," Ma same ligand during the day." A chiral the ligand is polyhistidine. This other tile recalls. "I sent him back to find out clock would be something very natural, system, they have shown—with under what he did wrong. I was sure it was an he adds, except that "I don't know of graduate student Maureen M. Tedesco experimental error." natural rhythms expressed as stereo and research chemist Naomi Sakai— After about 20 repetitions of the exper chemical changes." models the selectivity of potassium iment, "reproducibility convinced me" Maureen Rouhi MAY 31, 1999 C&EN
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