News
researchers have only been able to use it twice. "We have not found the ultimate polymer yet," says Powell. "We need to increase its affinity for cAMP to make it more practical. It's a novel finding in that it is the first time that a ligand has actually been imprinted into a polymer that contains both recognition and fluorescence sensing elements." The approach may be a first step towards developing a biomimetic sensor for aqueous cAMP; however, there are still some areas that need improvement. "Once we come up with something that is a bit more sensitive to cAMP, then we can try the same techniques to look at other second messengers." Britt Erickson
Facile estimation of partitioning coefficients of drugs Drug design is big business, and in the quest for new bioactive compounds many synthetic advances have been made with combinatorial approaches. The large number of compounds consequently generated creates great demand for reliable characterization of their physicochemical properties. One of these properties is hydrophobicity (a measure of a compound's ability to partition through biological membranes), which is estimated by measurement of the thermodynamic octanol-water partition coefficient (log P). The octanol phase mimics the hydrophobic biomembrane. Until now, the standard method for accurate measurement of log P has been the time-consuming "shake-flask" technique. This method typically takes one day per compound a timescale unacceptable to drug discovery teams. Recent advances by Patrick Camilleri and co-workers at SmithKline Beecham Pharmaceuticals (U.K.) with collaborators Melissa Hanna and Andrew Hutt at King's College London could change all that. Camilleri considers that "log P is frequently the most significant physicochemical parameter routinely considered in drug design." He and his research team have focused on developing a means for its rapid and reliable estimation. Three years ago, these workers were the first to use micellar electrokinetic capillary chromatography (MECC) for the determination of partition coefficients for drugs, and in the May 15th issue of Analytical Chemistry (p. 2092) they extend that work by reporting a rapid method for the prediction of log P with
Buckyball
breath test A humidity sensor fast enough to follow human breathing has been developed by California chemists based on the ubiquitous buckyball. The tough new material is far more sensitive in the lowhumidity region than current solid-state sensors and could eventually be applied in several analytical environments. Galen Stucky and graduate student Andrew Saab at the University of California-Santa Barbara have found that they can mediate the conductivity of a derivative of the buckyball (properly known as [60]fullerene) by exposing it to water vapor. They have fabricated the compound into a durable thin film, which operates over the whole humidity range but is especially sensitive to the low levels of humidity required for opto-electronics fabrication, according to Stucky. Chemists have added all sorts of doping agents and groups to fullerenes in an effort to affect electrical properties, but practical applications are still limited. "Research by [our] group on the diffusion and transport properties of Cgo suggested that there might be some mileage in making an ionicaUy conducting material," says Stucky. "Subsequent efforts were directed toward controllably reproducing the water-sensitive films."
reversed-phase HPLC and MECC for a wide range of drugs (acidic, neutral, and basic). The new protocol "combines die best features of reversed-phase HPLC and MECC," says Camilleri. "The system can therefore provide a very reliable estimate of log P." The ability of this system to provide rapid screening of mixtures of potentially diverse compounds is of enormous benefit to those involved in drug discovery. Both the HPLC and MECC methods are based on die same fundamental principle as the shake-flask system, indeed they can be viewed as automated versions of the same. Each involves primarily the measurement of the extent to which the test compounds distribute between an aqueous and an hydrophobic phase. The more hydrophobic a compound, the greater the association with the hydrophobic phase, and hence the more it will be "retained". Retention parameters (such as the capacity factor, k') determined
372 A Analytical Chemistry News & Features, June 1, 1998
^he team beSan kv using water vapor and oxygen to slowly oxidize a previously described potassium-doped fullerene under an intense xenon light. The exact conditions were arrived at by trial and error, but once they had established a preparation method they set about testing the film's sensitivity to water vapor (Adv. Mater. 1998,10,462-65). To avoid polarization of the material, the researchers recorded AC conductivity in an atmosphere of pure water vapor covering the pressure range 0.03-25 mbar. This corresponds to a range of about 0.1-100% relative humidity. In the lowest region, 0-5 % relative humidity, ,he material is up to six times more sensitive than some conventional materials. Stucky says that although the UV-vis spectrum of the film is not very different from that of pure [60]fullerene, the near-IR photoacoustic response of the bulk material hints at the presence of highly functionalized species with hydrogen and oxygen atoms, and hydroxy groups. "The unique fullerene nature of the material could be mediating the conductivity," explains Stucky. He adds, "The material certainly has potential for humidity sensing applications, although it will require a further R&D effort aimed specifically at technical applications before the real usability of the material is known." David Bradley
by HPLC and MECC should therefore be correlated with log P values. A conceptual advance made in this work towards obtaining the best estimate of the in vivo behavior of potentially bioactive compounds is to design the hydrophobic phase to resemble as closely as possible a biomembrane. A possible means of achieving this goal is by use of a natural biomembrane component, such as phosphatidylcholine. Camilleri and co-workers prepare the stationary phase for HPLC by cycling a 1-mM solution of lecithin (phosphatidylcholine) in methanol-water through the column for 24 h. This method, Camilleri says, "may lead to die formation of multilayers" that allow biologically relevant partitioning of the test compounds. Columns made in this simple way are very stable and last for weeks without degradation. The MECC system incorporated phosphatidylcholine bile acid mixed micelles in the aqueous buffer.
