science/
technology ^^233Miiicli^^^ Embraced by a foldamer Foldamers are oligomers with a strong tendency to adopt specific, compact conformations in solution. They are being investigated for various activities (see page 14). Chemistry professor Jeffrey S. Moore and coworkers at the University of Illinois, Urbana-Champaign, have
the researchers have used carbon isotope ratios in a sediment core taken from the ocean floor off the California coast to provide the first direct evidence that huge releases of methane from hydrates have reached the atmosphere at least four times during the past 60,000 years. The times of the releases correspond to periods of rapid global warming. Carbon in the hydrates has a distinctive isotope ratio, so the researchers can trace its incorporation into marine microorganisms whose remains eventually became part of the sediment core. Huge amounts of methane are currently contained in subocean hydrates, and models suggest that ocean warming of only a few degrees could trigger its release in some places.^
Monolayers assemble selectively on gold now found that when the phenylacetylene oligomer shown here [R = C0 2 (CH 2 CH 2 0) 3 CH 3 ] folds in a helical conformation, it can wrap around small molecules such as monoterpenes [J. Am. Chem. Soc, 1 2 2 , 2758 (2000)]. The binding occurs in a strict 1:1 stoichiometry with an association constant of about 60,000 M"1. This is greater than what is typically observed for 1:1 small-molecule/cyclodextrin complexes, Moore says. When the space in the foldamer cavity is reduced by adding methyl groups to the backbone, the association constant drops by two orders of magnitude, indicating that the binding occurs inside the cavity. And the binding is diastereoselective— that is, chiral terpenes preferentially bind to the left- or the right-handed form of the foldamer's helical conformation.^
Methane can escape from subocean hydrates Massive releases of methane from metastable cagelike structures of water molecules (methane hydrates) on the ocean floor have occurred in geologic history at the same time that the climate grew warmer, according to marine geology professor James P. Kennett at the University of California, Santa Barbara, and his colleagues [Science, 2 8 8 , 128 (2000)]. Earlier studies have shown elevated levels of methane in the atmosphere during the warm period of climate cycles, and release of methane from subocean hydrates had been proposed as one source for the greenhouse gas. In the new work, 48
APRIL 10, 2000 C&EN
Electrochemical oxidation of alkyl thiosulfates on gold electrodes can be manipulated to drive self-assembly of thiolate monolayers that selectively deposit on specific electrodes [Angew. Chem. Int. Ed., 3 9 , 1228 (2000)1. Gregory S. Ferguson and Michael S. Freund, associate and assistant professors of chemistry at Lehigh University, Bethlehem, Pa, and coworkers fashion the monolayers by pulsing anodic potential to a gold electrode immersed in a solution of an alkyl thiosulfate. The extent of the thiolate monolayer formed can be controlled by varying the applied potential and the number of pulses. The key advantage of the electrochemical approach over conventional strategies for monolayer assembly is that it can determine where the monolayer will form: Only electrodes at potentials high enough to oxidize the thiosulfate precursor can propel self-assembly, the team has shown. As a result, the electrochemical method could be used to prepare microelectrode arrays differentiated by monolayer composition and surface chemistry—a feat that could lead to the development of sophisticated sensor arrays, the researchers say.^
Swelling hydrogels act as microvalves "Smart" hydrogels that swell and contract in response to changes in their environment can serve as valves that regulate flow in microfluidic channels without any external control mechanisms [Nature, 4 0 4 , 588 (2000)]. David J. Beebe, assistant professor of biomedical engineering
at the University of Wisconsin, Madison, and chemistry professor Jeffrey S. Moore and colleagues at the Beckman Institute for Advanced Science & Technology at the University of Illinois, Urbana-Champaign, fashion tiny pillars of pH-sensitive hydrogels within transparent microchannels by photopolymerizing the precursors through masks, then washing away unreacted monomer. To create a device that sorts a fluid stream by its pH, they place pillars made from different hydrogels at the entrance to each branch of a T-shaped channel. The hydrogel gate at one branch expands at acidic pHs, blocking flow, whereas the hydrogel at the entrance to the other arm of the T swells when exposed to basic solution. The researchers also have designed a device that senses the chemical environment in one channel and regulates flow in another. This approach could be extended to antigen-responsive hydrogels that could serve as devices in self-regulated drug delivery or in biosensors, they write.^
Agent may be more selective than Viagra A research group at Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, N.J., has synthesized a potential drug that hits the same target as Pfizer's erectile dysfunction drug Viagra (sildenafil), but with higher potency and enhanced selectivity, according to an in vitro assay [J. Med. Chem., 4 3 , 1257 (2000)]. The compound (shown) inhibits phosphodiesterase type 5 (PDE5), the primary target of Viagra, but has much less tendency than Viagra to inhibit the
related enzymes PDE1 and PDE6, suggesting it might have fewer side effects. Viagra's adverse side effects include nausea, headache, facial flushing, and visual disturbances. Biochemistry professor Abdulmaged M. Traish of Boston University School of Medicine commends the skillful synthetic strategy used, but notes that the paper includes no preclinical data on the compound, making it impossible to comment on its potential. Several other companies are also pursuing drugs that could compete with Viagra.
