Open Combinatorial Chemistry in the Undergraduate Laboratory?

In a recent post with several valuable comments: Open Science in the Undergraduate Laboratory: Could this be the success story we’re looking for? Cameron Neylon brings together ideas on how undergraduates could do chemistry in parallel to explore a wide range of compounds which could be screened against biological targets relevant to malaria. I don’t know how many chemistry undergraduates there are worldwide – with India and China I’ll guess 1 million. Jean Claude has publicised a well known reaction – Ugi – which bolts together three different groups (call them X, Y, Z). You can buy 100 different variants of X (X1-> X100) and the same for Y (Y1-Y100) and Z (Z1-Z100). So you can in principle make 1 million compounds (100*100*100). Each undergraduate would do a slightly different reaction, purify the compound and record its spectra. The records would all be Open.
They have also suggested we can do theoretical calculations on these. With a modern machine this takes a few hours to get very good accuracy, and that could be run on the students’ own machines. We have developed CML-based technology as in CrystalEye which can represent this in semantic fashion. The whole material should take about a terabyte – not challenging by today’s standards.  And it could all be stored in Pubchem, or Chemspider or Amazon or even an institutional repository.
Of course not all reactions will work, and some of the undergraduates will make mistakes (that’s how education works!).  But it’s a great vision. The main problem is that most chemists are very conservative and undergraduates do the same experiment year after year. This would take some effort…
… but it would be worth it.

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5 Responses to Open Combinatorial Chemistry in the Undergraduate Laboratory?

  1. Yes for the person who runs the teaching lab this is definitely more work.
    That’s why I was thrilled that Brent was willing to put in the time and order the chemicals.
    The first lab starts tomorrow:
    In terms of purification, we’re sticking to isolation by filtration of a precipitate. Those reactions that don’t precipitate are discarded. That simplifies the protocol tremendously.
    For now, the best source to view all the pooled data for the CombiUgi project is this GoogleDoc – the Ugi Master Table:
    There are links to the original lab notebook pages with all the raw data for each entry
    Of the various libraries that we have been using:
    Library 3 has the list of Ugi products that we can make in my lab immediately (71K)
    Library 2 has the list of Ugi products that can be make from cheap starting materials available from Sigma-Aldrich marked as next-day shippable (500K)

  2. Daen de Leon says:

    I’ve developed a tool on top of OpenBabel which I’ve called a CombChem Engine (CCE). It reads pools of compounds, deprotection strategies and attachment chemistries and produces a bunch of compounds according to those rules. The tool itself was written for a biotech client of mine, so I can’t release it publicly. However, I modified some of the OB source in order to get it to work, and I will make those alterations publicly available.

  3. pm286 says:

    (2) Thanks, although I’d welcome clarification. Are you saying that you have modified OB to give the same functionality? If so I assume you have committed and the OB community is happy. Are you also saying that you have an Open set of attachment chemistries, deprotection strategies, etc.? Because if so, and it makes sense, I may well wish to integrate the functionality into CML (which itself does a simple sort of combinatorial molecule generation but without the additional bits you mention).

  4. Daen – let us know when you make it available. Rajarshi Guha has set up a web service to generate Ugi products from lists of starting materials:
    It would be great to have more such services available to the public

  5. Yes, that would be a great tool to have and if it can be set up as a webservice as well that would be brilliant. To me it is important that this is not just enabling a specific project but that the tools can enable other open projects to go forward as well.

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