Sunday, March 23, 2008

Expanding the UsefulChem Collaboration to Teaching Labs

A few weeks ago I received a very interesting email from Brent Friesen at Dominican University. He mused:
I am trying to put together a bridge between the type of opensource research you are instigating and the traditional Sophomore Organic Chemistry lab. There are over 4,000 college and universities in the United States - all of them teach Sophomore Organic Chemistry lab. How can we harness this resource? .....

SOC labs must fulfill 4 criteria:
1) inexpensive reagents and equipment
2) fit into the time constraints of 1 3-hour period per week.
3) Must be a robust reaction with fairly stable products. It doesn’t have to be “foolproof” but that helps.
4) Compatible with equipment, glassware, procedures that student know how to use and do.

Bottom Line: I am definitely interested in developing collaborative projects, especially if they can be performed as part of a Sophomore Organic Chemistry laboratory curriculum.
This is extremely encouraging news for open scientific collaborations and I am very impressed with Brent's initiative! It certainly is more work for him compared to maintaining the status quo.

Kevin Owens and I have discussed this possibility for some time now and he is willing to contribute by carrying out mass spectrometry if required.

Brent and I further discussed the applicability of the Ugi reaction that we perform in my lab because of its simplicity - 4 components are mixed together in methanol at room temperature and a Ugi product often precipitates within days, requiring only filtering to isolate. (see EXP150 for a good example)

However, one major limitation of the Ugi reaction for a teaching lab is the terrible stench of most isonitriles, one of the four key components. One way around this is to use isonitriles that don't stink, such as TOSMIC.

So as a starting point, we would like to start with a Ugi reaction which involves TOSMIC and has lead to a precipitate in our lab. There is only one example so far: 171H.

According to the lab notebook, all starting materials dissolved easily and a precipitate appeared after 2 days. The precipitate has not yet been isolated and characterized. Hopefully it will prove to be pure Ugi product, as other similar Ugi reactions have done.

It turns out that many of the top ranking compounds from Rajarshi's falcipain-2 docking run (V2) contain TOSMIC as the isonitrile. Phil Rosenthal at UCSF is still up for testing compounds for anti-malarial activity. Wouldn't it be a testament to the power of open collaborative science if a decent anti-malarial lead was uncovered through the routine teaching of undergraduate organic chemistry labs?

At the very least I'll bet it would be rewarding for the students involved.

Brent has placed the orders from Sigma-Aldrich and is moving full steam ahead. He recently wrote to me:
You know, I'm ready to dance and you are the only dance partner who seems to be ready and willing. Let's figure out a way to adapt the Ugi reaction to Sophomore Organic Chemistry laboratory and give it a try!

I would like to plan it for the week of April 7 and the following week...
Does not give us much time, but it can be done.
Keep track of Brent's activities on his blog.

TOSMIC InChIKey CFOAUYCPAUGDFF-UHFFFAOYAC InChI=1/C9H9NO2S/c1-8-3-5-9(6-4-8)13(11,12)7-10-2/h3-6H,7H2,1H3

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At 11:14 AM, Blogger Cameron Neylon said...

This is very very cool. Will be great to see how this works out because one could easily see it spreading out internationally. For instance at Southampton there is a synthetic chemistry summer school where students spend four weeks on 3-4 different projects usually lead by pharma companies, but you could see this fitting in.

It will be great for the students to see their compounds being screened - this is something the students at Southampton really appreciate from the summer school (I think they even got a hit against a kinase screen once). But even just the information on what products precipitate or not would be great.

Look forward to seeing more on this (and have added Brent's blog to my list).

At 11:53 AM, Blogger ChemSpiderMan said...

I started a conversation up with Brent about a week ago (offline). Are you intending to put the analytical data up on ChemSpider? We've added the ability to load images etc so you could put up reaction details there etc and annotate. I think we need to add a "Add to Report" section and allow people to edit the report etc. (Anyone to read and only the depositor and approved collaborators to edit..what do you think?)

At 1:06 PM, Blogger Jean-Claude Bradley said...

I assume you mean Jeremy Frey's project with the summer students? That is definitely a nice example. One difference here is to try to keep everything open. If I recall correctly Jeremy was limited by the pharma companies as to how much he could disclose.

At 1:56 PM, Blogger Cameron Neylon said...

Actually not quite, what I had in mind is a summer school where a select group of around 20 or our best organic chemistry students each year go into the teaching labs to do synthesis for three to four weeks. The students are selected from the cohort and do usually one week of induction on slightly more advanced synthetic technique than they have seen before. Then they move on to one week projects that are usually driven by pharma companies who donate the time of the demonstrators and some of the reagents. Usually this involves very old projects which are in the public domain for obvious reasons. Essentially they tend to be established routes from existing med chem programmes where there is some value in genearting some additional diveristy in their in house libraries by adding on a bunch of things at the last step.

What I was thinking was that the comb-ugi plus some screening of some description could be a nice week for these students. There wouldn't be a problem with making it open per se and one could imagine setting up a UsefulChem style WIki to record the results. There is a computer lab nearby with plenty of terminals. The catch would be funding it - the summer school works on the basis that the pharma companies can supply the personnel support and chemicals from inventory - it is soft money for them. To do this we would need to find the money to cover demonstrators time and chemicals as well as the costs of analysis and screening.

Nonetheless one could imagine rolling it out as an organised programme and inviting in chemistry schools anywhere to take part. Kind of 'drug development@home' kind of thing. The deal being that the methodology is provided and reasonably worked out, the compounds made and the analysis data go into an open library of compounds and data, and then the students get feedback on the screening results. If there were enough people about prepared to screen the compounds (which I suspect is the expensive bit in the end) then it could be a really interesting programme (maybe Gates FOundation or Google might fund it?). In my lab we would screen e.g. for HIV protease and Sortase (S. aureus target) inhibition, possibly a few others. If there was some funding available to support it I would imagine a lot of people would be interested in getting access to the library and might not be too concerned about openness being a condition.

I guess see how it works out with Brent in the first instnace anyway. See what the potential problems are in actually makin it work on the ground. We could possibly look at doing a week at the Soton summer school next year and try to get some UK funding for it?

At 3:05 PM, Blogger Jean-Claude Bradley said...

Actually the screening for now is free for falcipain-2, general anti-malarial activity and NCI's anti-tumor activity testing. I would not expect the numbers you are proposing to be too onerous. The libraries that we screened were chosen with the cost of starting materials in mind so that cost should be on the low side.

But certainly funding helps with everything. It is certainly worth investigating.

At 10:03 AM, Blogger Jean-Claude Bradley said...

I would like to encourage Brent's students to upload spectra and images for isolated pure compounds. The policy in my lab is that we'll upload all clean spectra onto ChemSpider. But the majority of spectra taken are not uploaded because they have some problem - not pure enough, phasing issues, concentration problems, etc. All those spectra are still uploaded to the UsefulChem server of course. If there is a mechanism to upload these to ChemSpider lets talk.

At 1:35 PM, Blogger anna croft said...

Does anyone know if screening against TB targets is also free?

At 5:16 PM, Blogger Jean-Claude Bradley said...

I have not found anyone to do TB testing yet.


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