Olympic molecule gets its picture snapped This year's Olympic Games and Interna tional Chemistry Olympiad are over, but Olympic feats continue to be performed in the laboratory. The latest example concerns—appropriately enough—a molecule called olympiadane, so named because it consists of five macrocycles interlocked in a chainlike fashion, remi niscent of the emblem of the Olympic Games. After much effort, British re searchers finally have succeeded in ob taining an X-ray crystal structure of this unusual pentacatenane. "If s a very appealing structure," re marks chemistry professor J. Fraser Stoddart of the University of Birming ham, England, who spearheaded the effort. "And just to see five interlocked rings is fascinating in itself." Olympiadane was first prepared and isolated in very low yield in 1993 by David B. Amabilino, then a postdoctor al fellow working in Stoddarf s lab [Angew. Chem. Int. Ed. Engl, 33, 1286 (1994); C&EN, Aug. 29,1994, page 28]. Amabilino and Stoddart used a self-as sembly process in which a cyclophane (shown here in black) containing π-electron-accepting bipyridinium units is clipped around two macrocyclic polyethers (yellow and green) contain ing π-electron-donating 1,5-disubstituted naphthalene rings. This intermediate, a [3]catenane, is elaborated into the final [5]catenane by clipping a smaller cyclo phane (blue or red) containing bipyri dinium units onto each of the two poly ether rings. Once the synthetic route was worked out, the Birmingham group faced an even bigger challenge: making enough olympiadane to crystallize it and obtain a single crystal suitable for X-ray struc ture analysis. That goal was achieved only recently by Ju Young Lee, a post doctoral fellow in Stoddarf s lab. Lee figured out how to make the [5]catenane in yields as high as 37%, based on the precursor [3]catenane. The secret to his success was running the reaction at a pressure of 12 kilobars in dimethylformamide solution for six days. The X-ray crystal structure of the [5]catenane then was unraveled by Stoddarf s long-time collaborator, Da vid J. Williams, professor of structural chemistry at Imperial College of Sci
ence, Technology & Medicine, London, and postdoctoral fellow Stephan Menzer. A full paper on the structure deter mination will soon be submitted for publication. "One of the most striking features of the structure, as revealed by the X-ray analysis," Stoddart and Williams point out in a press release, "is the intimate relationship between the π-electron do nors and acceptors" in the interlocked rings. "When you get a crystal structure [like this], you see the reason why you're able to put [the molecule] to gether," Stoddart tells C&EN. "You see these weak interactions—π-π stacking interactions, edge-to-face interactions, the CH"O hydrogen bonds—which presumably are used during the selfassembly process" as segments of rings
that are in the process of forming inter act with rings that are already formed. "That's why, essentially, you get it to assemble the way you do." In addition to the [5]catenane, the synthesis also provides the [6]catenane and [7]catenane, each in about 27% yield; these result from clipping an ad ditional cyclophane onto one or both of the polyether rings, respectively. The Birmingham and London groups are now working to get a crystal structure of the [7]catenane. Says Stoddart, "Both David and I will be even more intrigued when we see the [7]catenane structure because one has to wonder: How do you squeeze another couple of rings through the yellow and green rings? It doesn't look all that easy. Yet it does happen." Ron Dagani
Chocolate may mimic marijuana in brain Chocolate lovers won't find this news too much of a surprise: The rich, sensu ous confection contains compounds that turn on the same receptor in the brain as marijuana. Biochemist Daniele Piomelli and co workers at the Neurosciences Insti tute, San Diego, have isolated small quantities of anandamide—the ethanolamide of arachidonic acid—from chocolate and cocoa powder [Nature, 382, 677 (1996)]. The compound is thought to be the natural ligand for the cannabinoid receptor, the receptor that binds tetrahydrocannabinol (THC) and
Anandamide
is responsible for the high induced by marijuana. "The discovery of anandamide in chocolate is totally unexpected and may be relevant to the well-known 'chocolate craving,' " comments Ra phael Mechoulam, professor of medici nal chemistry at Hebrew University, Jerusalem. Mechoulam first discovered anandamide in pig brain in 1992, nam ing it from the Sanskrit word "ananda," meaning bliss. The chocolate research is something of a side trip for the researchers at the Neu rosciences Institute, which is actually lo cated at Scripps Research Institute but is independent and funded by a grant from Sandoz. Piomelli's group has been studying the formation and inactivation of anandamide, looking for leads for drugs to relieve pain and depression. SEPTEMBER 2,1996 C&EN 3 1
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"We got to wondering about chocolate," he tells C&EN. "The pharmacology of chocolate is still very much unknown. It's difficult to say if it's a food or drug or something in between. Anandamide is a fatty acid derivative and chocolate is very rich in fats. We wondered if perhaps what makes chocolate so special is tied to the cannabinoid system." Once they looked, the researchers found anandamide in concentrations of micrograms per gram of chocolate. They also found much higher amounts of two related compounds: the ethanolamides of oleic and linoleic acid. "We were intrigued," says Piomelli. "These compounds do not act on the cannabinoid receptor. But they are both fairly potent reversible inhibitors of the enzyme that inactivates anandamide by cleaving off the amide group." Thus these constituents of chocolate may prolong the lifetime of anandamide by inhibiting its inactivation. Piomelli is quick to point out that his group's in vitro experiments do not ad-
Students use rocket to study ozone A rocket-borne experiment to study stratospheric ozone and other atmospheric constituents has been performed by some 50 students from Colorado universities. The High-Altitude Ozone Measuring & Educational Rocket (HOMER) was launched Aug. 12 by the National Aeronautics & Space Administration from its Wallops Island, Va., flight facility. After being carried to an altitude of 60 miles by a Nike-Orion sounding rocket, HOMER's payload was recovered in the Atlantic Ocean. Science data gathered during the flight were also transmitted by radio. The experiment was part of NASA's Student Launch Program, which provides students hands-on experience in developing scientific suborbital payloads and analyzing data from them. Students from Colorado State University, Fort Collins, and the Boulder, University of Colorado, Boulder, students Sean Dougherty (from left), Linda Cuplin, and Patnck Adam prepare HOMER payload for subsequent launch on suborbital sounding rocket (far right). 32
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dress the question of whether anandamide ingested as part of a chocolate bar actually has an effect on the brain. Dale G. Deutsch, associate professor of biochemistry and cell biology at the State University of New York, Stony Brook, is skeptical. "Can that chemical get from the stomach to the brain?" he asks. Deutsch, who first described the amidase that inactivates anandamide, points out the enzyme in the liver most likely would break the compound down first. Piomelli says there's a lesson to be learned whether or not the fatty acid amides turn out to be behind the pleasant sensations from chocolate that cause some people to say they are addicted to the stuff. "If you can tinker with the endogenous cannabinoid system by inhibiting the inactivation of anandamide, you might be able to design drugs that retain the valuable properties of marijuana like analgesia and euphoria, while eliminating undesirable effects like loss of motor control." Pamela Zurer
Denver, and Colorado Springs campuses of the University of Colorado worked on the project starting in March 1995 under the Colorado Space Grant Consortium. HOMER was the consortium's third sounding rocket mission, following successful ozone-measuring flights in 1992 and 1994. "We learned a lot about preparing missions from the last mission," says Ellen Riddle, a graduate student at Boulder and coproject manager. "This payload is more sophisticated, with more advanced science instruments and data support systems." The payload included an ultraviolet spectrometer and three photometers to measure local ozone abundance at various altitudes. Unlike the previous missions, it also sought to measure nitric oxide and atomic and molecular oxygen, which affect ozone levels. HOMER aimed to demonstrate use of low-cost, high-performance UV imaging charge-coupled device (CCD) technology—which has never flown before—to enable measurement of the additional atmospheric constituents. The CCD detector, developed at the Jet Propulsion Laboratory in Pasadena, Calif., shows enhanced responsivity in the UV region, allowing measurements from 210 to 260 nm. The previous two missions bore UV and visible light photometers, which permitted stratospheric measurements at altitudes of 20 to 50 km. HOMER carried visible, infrared, and UV photometers. The IR instrument extended the range to the mésosphère, allowing measurements between 25 and 95 km. Consortium officials say the instruments all performed as planned. Analysis of the data will be completed later this month. Richard Seltzer
