Reaction Attempts on ChemSpider

Just as we have done with the Open Notebook Science Solubility Challenge, we are adding more structure to the UsefulChem project.

This is a little bit more difficult because the UC notebook represents mainly chemical reactions, while the ONSC data are simply solubility measurements. Since most of the UC reactions are Ugi reactions, we have been keeping summary data in the CombiUgi Google Spreadsheet, which is completely specialized for this reaction and variations in our reaction conditions. This lets us search or sort by reactant, concentration, solvent, etc. However, we cannot do substructure searching directly using the CombiUgi sheet and we cannot add other types of reactions.

In order to enable substructure searching and add other reactions, Antony Williams has created 2 new data sources in ChemSpider: Attempted Reactions - Reactants and Attempted Reactions - Products. The data represented in the CombiUgi sheet has been restructured into 2 new Google Spreadsheets: RXIDs Reaction Attempts and Reaction Attempts.

Both of these sheets use a common Reaction ID to tie together an unlimited number of reactants and products (Reaction Attempts) and other pertinent reaction conditions (RXIDs Reaction Attempts), such as the concentration of the limiting reagent, the solvent, yield, notes, etc.

Currently only the data in the Reaction Attempts sheet has been imported into ChemSpider. But this alone gives us new functionality: we can perform substructure searches for either reactants or products.

For example lets say we want to search for all reaction attempts using aromatic carboxylic acids. First we simply do a substructure search on ChemSpider drawing benzoic acid and selecting Attempted Reactions - Reactants as the Data Source.


This pulls up 8 compounds that were used as a reactant at least once.


Clicking on one of these hits brings us to the ChemSpider entry. Selecting the Syntheses tab in the Data Sources shows links to the lab notebook pages where this compound was used.


The system is configured to accept reactions with fully characterized products to reactions where products were not isolated or even reactions in progress. I'm not using the term "failed reaction" because the term has no meaning without the context of the objective of the reaction. In our Ugi reactions we are typically looking for the product to precipitate out. By our criteria, reactions where no precipitate was observed after a few days would be classified as "failed". However it may well be that product was formed but did not precipitate. Even when product is obtained, some might consider 30% isolated yields to be failures, while others would not. Context is everything in qualifying success.

But even with a clear definition of success, many reactions are simply neither successful or failures. Reactions in progress fall into that category. The student may have even completed the reaction but not yet analyzed the results. But that doesn't matter so much if the raw monitoring data has been provided.

The general structure of this database means that we can add not only our reactions but those of anybody. Even in cases where someone does not have an Open Notebook, just providing a link to contact information of the researcher could be very useful to start a conversation. In that case the system would function more as a social networking platform - connecting researchers who work on similar molecules.

I don't think people are willing to do extensive write-ups for what they consider to be "failed experiments". However, if all that is requested is the list of reactants and target products that may not be such a burden if it potentially means connecting up with another researcher who can help or even start a new collaboration.

Currently ChemSpider does not take into account the information in the RXIDs Reaction Attempts sheet but we hope to be able to make use of that at some point. That would let us do more sophisticated searches like - search for any reaction attempt where an aromatic carboxylic acid was reacted with an aliphatic amine in methanol.

Andrew Lang has also provided the information of the 2 spreadsheets as XML:
http://showme.physics.drexel.edu/onsc/Services/OData.svc/Reactions/
http://showme.physics.drexel.edu/onsc/Services/OData.svc/ReactionCompounds/
[Note: if viewing on FireFox select View Source to see all the XML]

We will likely use these live feeds for performing more sophisticated queries and we welcome others to use them for any purpose.

Ugi Reaction on MiniMapper - Trial 1 Preliminary Results

After receiving the MiniMapper two weeks ago we now have some numbers to look at from Trial 1.

The idea here was to repeat a Ugi reaction known to work in methanol at 0.5M concentration (EXP099) and explore the experimental space varying solvent, concentration and an excess of some of the reagents.

All 48 reactions gave precipitate (EXP189). We still have to optimize the lighting and camera angle to see this clearly for all tubes:

In reviewing the results I noticed an inconsistency between the experimental design and the information in the GoogleDoc used to plan the details of the experiment. But because the MiniMapper stores the log of its actions in an XML log file, Khalid was able to make corrections to the worksheet.

Based on the weight of product and the limiting reagent, a yield for each reaction was calculated (column AC).

The best 4 yields (48-61%) were found for 4:1 acetonitrile/methanol solutions at the lowest concentration (0.1 M). It is counterintuitive that a multi-component reaction should work better at lower concentration but this is an effect that I noted previously.

Ironically, the absolute lowest yield (1.4%) was found for the 0.5M methanol reaction that was supposed to be the positive control!

This may be due to a malfunction in the delivery of one of the reagents. However, the other reactions carried out at this concentration in methanol were all low yielding (10-15%), compared to when it was run manually in EXP099 (37%).

I must stress that these results are very preliminary since we have not yet shown that the isolated materials are all pure Ugi products. As the NMRs come in I'll update the status.

But I think that this was a good first trial to demonstrate what kind of questions can be asked with the power of automation and the importance of reporting automated logs in Open Notebook Science.