Editorial
Analytical chemistry in parallel
T
his August's Gordon Conference on Analytical Chemistry, ably chaired by Tim Harris of SEQ Ltd., focused on the analytical chemistry challenges offered by combinatorial chemistry. There was a vigorous exchange of ideas and information between an excellent group of guest speakers from die combinatorial chemistry field and the attendees from the analytical chemistry community. I thought the exposure of analytical challenges and needs was well accomplished, and I was impressed by some differences in their character from traditional approaches to analytical problems. One prominent example goes by die acronym "HTS" for high-throughput screening. Combinatorial chemistry is a style of synthesis (there are actually several styles, such as split-and-pool and parallel) in which selected building blocks are combined in different ways so as to produce large numbers, or libraries, of new molecular variants much more efficiently than is possible by traditional synthetic approaches. (Chem. Rev.. March 1997, ,povides sn excellent background.. The synthetic reactions used are not "elegant", but the conceptual dunking in combinatorial chemistry is. It has given drug discovery units in pharmaceutical companies a crank with a very long handle, producing in a few days a 50,00Ocompound library of new molecular structures. Having accomplished that, how does one determine which compounds show activity of die kind sought (the assay problem), and then what are die specific structures of diose diat do? Complicating that question, most combinatorial methodologies yield 0.1 to micromole quantities of product, which are localized on polymer beads, plastic "pins", or in microtiter plate wells. Thus, the problem demands respectable analytical sensitivities. An analytical bottleneck instantly looms; solutions to the HTS problem invite parallel thinking. Analytical chemists are accustomed to serial tiiinking, that is, instrumental methods that measure one sample at a time. The Human Genome project has produced some forward thinking about parallel analysis (multiple samples at atime);the HTS problem will surely push that concept further and expand the com-
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petent methodologies. Simultaneous separation of multiple (10-100) samples is known for gel, slab, and capillary electrophoresis, as is multiple detection by electrochemistry and optical fibers. However, I am not aware of analogous experiments for UV-vis or IR spectroscopy, gas chromatography, mass spectrometry, or NMR spectroscopy. And it is not clear that such pioneer analytical chemistry is presently part of the drug discovery effort. It seems to me that a more substantial and generic level of drinking about parallel analysis in analytical chemistry needs to be developed. In terms of concepts, microfabrication and multiple transduction along with comparisons to alternative fast serial analyses also nee(j to be developed We must also educate our students in these concepts This is the analytical frontier that I wish to bring out in this editorial The present intensive pharmaceutical drug discovery effort will continue as long as ii delivees on its sromise eo accelerated discovery of drug leads. Maybe, at some point, a period of satiation or a new type of effort wiil let in. However, I suspecttiiatdie future of combinatorial chemistry and its parallel analysis needs is not solely confined to drug discovery and associated phases of syntiiesis optimization. Combinatorial chemistry has die obvious promise for discovery of new reaction catalysts, solidstate materials (see Science e997,277,474-75)) biocides, and the development of selective binding or reaction chemistry for chemical sensors. I believe tiiere are and will be many opportunities for creative thinking about parallel analysis springing from combinatorial experiments I hope that more analytical chemists begin to tiiink about turning suchtilingsas imaging techniaues for multiple spectra acquisition; electrochemical piezoelectric element and surface olasmon resonance arrays; nested ion traps and NMR mirrnrnils; and parallel mirrn-
into more fact tiian
Analytical Chemistry News & Features, October 1, 1997 5 7 5 A
