ChemNews.Com VOL 9 NO 3

Combinatorial chemistry is quickly changing from the new frontier of chemistry research to a widely practiced methodology. In the field's early days, chemists and IT staff spoke of the "combinatorial explosion" that could easily result in vast libraries that would overwhelm any software yet developed; a five-step synthesis with 20 reagents at each step would result in 3.2 x 106 products. However, researchers quickly realized that the synthesis of such huge libraries caused stress in other areas of the synthesis process such as the problems relating to the deconvolution of huge mixtures.

Taking a step back from the initial confusion created by the contemplation of enormous libraries, many researchers realized that the automation of traditional synthesis techniques could still result in dramatic productivity increases. Whereas a chemist synthesizing one molecule at a time might synthesize three or four molecules in a week, that same chemist utilizing parallel synthesis techniques could synthesize 100 to 2000 pure compounds in the same time. This in itself represents a massive productivity enhancement. As this realization has become more widespread and as equipment and methods have matured, more and more research projects have begun utilizing parallel synthesis techniques.

Success breeds success. While combinatorial chemistry was once the preserve of specialty software, a huge number of ChemDraw users began to ask for combinatorial chemistry functionality within the ChemOffice suite. CambridgeSoft is pleased to announce support for combinatorial chemists with an extension to the ChemOffice suite. The combinatorial extension to ChemOffice is designed for the increasing number of chemists who seek to utilize combinatorial techniques to build libraries of reasonable size on a weekly basis. Since most of these chemists manage their combinatorial experiments with spreadsheets such as Microsoft Excel, the ChemOffice solution integrates ChemDraw with Excel and thereby provides combinatorial chemists with the chemistry functions they require inside the software they prefer to use.

Synthesis Based Approach

Nothing is more natural than drawing a reaction or synthesis scheme inside ChemDraw. ChemDraw has the chemical intelligence to understand which molecules are products and which are reagents in a given synthesis step, and the ChemFinder component of ChemOffice has the smarts to search through lists of reagents, automatically clip off R-groups and put them back on product molecules. ChemFinder's chemistry awareness extends to stereochemistry allowing for the support of stereoselective reactions and syntheses, ring/chain topology and other sophisticated representations of different kinds of reactions and molecules.

The representation of combinatorial libraries in terms of their underlying chemistry offers many advantages when compared with other approaches. Cyclizations and rearrangements are represented with ease with a reaction approach even though this kind of chemistry is badly handled by systems relying on generic representation of reaction products.

Using Excel to Manage Components

ChemDraw supplies the drawing capability. ChemFinder, behind the scenes, supplies the chemistry smarts. Excel is the software that holds everything together. Excel is an excellent place to manage lists of reagents, prepare files for synthesizers and analyze columns of results. If only it had the chemistry smarts to enumerate molecules, display, search structures, etc. ChemOffice provides exactly this kind of functionality.

The main organizational unit for library synthesis is an Excel workbook. The first page of the workbook contains the ChemDraw generic reaction scheme. ChemDraw interprets this scheme and makes worksheets for each generic reagent. Users load reagents into the appropriate sheet directly from ChemFinder and ChemACX, a database of 250,000 reagents available from vendors around the world. From here, users perform calculations on the selected reagents and edit the list in various ways. To enumerate the library, all that is required is to indicate which reagent is used for which run. ChemOffice does the rest of the work. It creates a runset summary sheet that shows the specific reagents selected for a given run of the synthesis as well as a product page for the runset with all the molecules synthesized in the given run. The pictures displayed are real chemistry objects stored in Excel that can be searched by substructure.

Reagent Selection

The ChemACX database of over 250,000 compounds available from over 200 suppliers, which is included in ChemOffice, is an ideal application for reagent selection. ChemFinder's search engine provides a powerful way for users to search through this database of reagents and ultimately decide which ones they would like to incorporate in combinatorial experiments. ChemFinder also provides ways to conveniently manage other reagent databases, such as browsing or merging vendor files. Once users have isolated the reagents they would like to use, they simply load the current ChemFinder list directly into Excel in a fast and smooth operation.

Summary

ChemOffice provides the most comprehensive set of combinatorial chemistry software available today. Draw reactions in ChemDraw, find reagents with ChemFinder and design experiments in Excel. ChemOffice's unsurpassed level of integration between products and the smart and natural reaction-based approach to synthesis set the new standard for usability and effectiveness for combinatorial chemistry software.