Friday, May 30, 2008

MiniMapper in Lab

As I mentioned previously, Mettler-Toledo is giving us a trial with their MiniMapper/MiniBlock system. Tom Osborne was in my lab yesterday to set it up. We got as far as setting up the software to recognize the positions of bottles and racks and pumping through some methanol.

Once we're set up it looks like we'll be able to come pretty close to just copying columns from the Google spreadsheet of planned experiments to the MiniMapper software. This will make it very convenient for crowdsourcing Ugi experiments.

Actually the worksheet for trial #3 is already set up to accept suggested experiments from anyone - no login required. Just note your name in the contributor column and put in a little explanation for your reasoning. For example, after looking at the master table of Ugi reactions, you may have a hypothesis that aromatic aldehydes lead to Ugi product precipitates at 0.5 M concentration in methanol. Just set up a dozen experiments probing that question. See the MettlerTrial wiki page for more info. I'll explain more about this later but if anyone wants to discuss collaboration contact me.

We have the capacity of doing 96 experiments in parallel but Khalid will probably start with a dry run with pure methanol or a small section from Trial #1.

Tom made a good point about how organic chemists need to think differently when designing experiments in parallel with automation. We have done parallel runs in vials but it gets tricky for people to keep track of everything. Machines are much better at this type of thing. You have to ask different questions when faced with 96 reaction tubes vs. a round-bottomed flask.

And it looks like the MiniMapper software keeps a log in XML format - obviously more on that after our first trial...

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Friday, May 23, 2008

NMR prediction on ChemSpider

As Tony recently mentioned, there is a new button on ChemSpider to predict H NMR spectra based on the web service:

To give it a spin I am posting the experimental spectrum of Ugi product UC-150D underneath the predicted one.

This is going to be extremely helpful and yet another reason for using ChemSpider in active chemistry research. However, this tool does not replace the need for understanding how to interpret NMR spectra.

First, two of the predicted peaks - the phenanthrene H at 8.5 ppm and the benzylic H at 5.7 ppm - are off by almost half a ppm. Second, the algorithm does not take into account the diastereotopic nature of the methylene group centered at 4.8 ppm. This is predicted to be a singlet but appears, as expected, as a pair of doublets.

With this new tool there is a danger that students might think that they don't need to learn the finer details of NMR analysis since the predicted spectrum just pops up so conveniently. I hope people will report on what they find to be most and least reliable as they work on real problems.

The beauty of ChemSpider is that both the theoretical and experimental spectra can be stored in the same record. Yet another reason to continue to routinely upload our spectra.


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Tuesday, May 20, 2008

Not a Ugi Product

As I mentioned previously, one of the objectives of our research is to determine the conditions required for precipitation of pure Ugi products. Until recently, every precipitate we obtained could be characterized as the expected product.

It looks like the situation is not so simple.

For example consider Khalid's attempt (EXP171) to make Ugi product 171 H:

A nice precipitate was obtained...

But it does not correspond to the expected product. For one thing the tosyl group is missing - no non-exchangeable protons past 7.0 ppm. It clearly has the 3,5-dimethoxybenzaldehyde and possibly the methylamine and 2,4,6-trihydroxybenzoic acid components. It is insoluble in all common solvents except for DMSO. Although I'm not completely satisfied with the integration of the H NMR, the MS seems to match an iminium salt:

If this is the case it may be because of the significantly increased acidity of ortho-hydroxybenzoic acids. 2,6-dihydroxybenzoic acid has a pKa of about 1.5 (Papadopoulos 1991), compared with benzoic acid's 4.2 value.

The problem may be with the isonitrile component TOSMIC. However, according to Chris Hulme, it should participate in Ugi reactions, even if it gives lower yields.

We'll just have to do more examples and see if a pattern emerges.

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Internet-based tools for communication and collaboration in chemistry

Antony Williams just published an article in Drug Discovery Today:
Internet-based tools for communication and collaboration in chemistry

Web-based technologies, coupled with a drive for improved communication between scientists, have resulted in the proliferation of scientific opinion, data and knowledge at an ever-increasing rate. The availability of tools to host wikis and blogs has provided the necessary building blocks for scientists with only a rudimentary understanding of computer software science to communicate to the masses. This newfound freedom has the ability to speed up research and sharing of results, develop extensive collaborations, conduct science in public, and in near-real time. The technologies supporting chemistry, while immature, are fast developing to support chemical structures and reactions, analytical data support and integration to related data sources via supporting software technologies. Communication in chemistry is already witnessing a new revolution.
There is a detailed description of UsefulChem with a screenshot of EXP148 on Figure 2, where one of our Ugi products is characterized. This is another fine example of extensive interlinking between the worlds of peer-reviewed literature and Web2.0 content, including making use of Nature Precedings in the references.

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Saturday, May 17, 2008

UsefulChem Automation Trial with Mettler Toledo

Kevin Owens and I have been looking into equipment to automate some UsefulChem experiments.

This is something that I feel strongly will become important in Open Science applications, especially as it relates to Open Notebook Science. I think it is one of the paths of least resistance for the automation of the scientific process.

Industry is automated to the gills but it will probably be easier to convince academic practitioners of Open Science to automate their procedures rather than to get industry to open their data. Can you imagine a company allowing crowds to design and analyze experiments run on their machines? That is what we've been proposing and it would be difficult to reconcile that with a business model based on IP protection.

In that NSF proposal, we planned to use ChemSpeed's technology. Kevin and I recently visited ChemSpeed at their Princeton location and we were impressed with the capabilities of their reactors. We're in the process of planning a trial run of the Ugi reaction on their system and we'll post on the progress of that on this UC wiki page. The idea is to couple a digital camera within the robot's workflow to be able to generate results comparable to those manually generated by my students.

ChemSpeed's systems are quite powerful but also expensive (200-400K). In order to take advantage of more funding opportunities, we've also been looking at Mettler-Toledo's MiniMapper/MiniBlock solutions. We're planning this out openly on this wiki page - any feedback is welcome.

I've had a good discussion with Frank Schoenen at the University of Kansas, where they run both systems as part of servicing the NIH Roadmap Program. Based on his feedback I think this trial run should be successful.

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Thursday, May 15, 2008

Google Custom Search for Open Notebook Science

There has been a discussion recently on Michael Nielsen's blog about using a Google Custom Search for Open Notebook Science. Starting with UsefulChem, ChemTools (Cameron Neylon), OpenWetWare and Gus Rosania's 1CellPK, I created a search:

More sites can be added by volunteers. It will only work for sites that are accessible by a simple url (without a login).

Give it a spin by searching "malaria" or "protein".

We've already been using the Google Custom search for UsefulChem and it really works well - see the search box at the top of the UC wiki main page. It is also useful for teaching - for example to aggregate high level content about organic chemistry.

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Friday, May 09, 2008

SciFoo 2008

Just got my invite for SciFoo 08 (August 8-10) - I look forward to another intense meeting and catching up with friends and collaborators!
Last year was truly enlightening.

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Wednesday, May 07, 2008

Rod's Pulse Podcast on Better Chemistry through E-Learning

Rodney B. Murray interviewed me last week for his educational podcast:

Monday, May 05, 2008

X2 Project

I was asked by the Institute for the Future to highlight a dozen "Signals" that may point to new trends in science as part of the X2 Project:
Today, science is entering another period of accelerated change, thanks to the growth of the Internet and dawn of pervasive computing; the explosive growth of new sciences like genetic engineering, nanotechnology, biotechnology, and simulation; the rise of new scientific powers in the developing world, the revival of amateur scientists, and the growth of citizen science movements in the United States and Europe; the growth of new institutions supporting scientific research and innovation, and changes in the structure and funding of universities, government, and corporate R&D labs. Science in 2025 and 2050 is going to look very different than it does today.

To map and make sense of all these changes, the Institute for the Future (IFTF) launched the X2 Project in late 2007. The purpose of X2 is to identify future disruptions, opportunities, and competitive landscapes related to the content and dynamics of global science and technology innovation; to develop a new platform for understanding global innovation trends; and to present this information to policy- and decision-makers, as well as the general public, in a useful form. The project conducts its research online, through an innovative experiment in open forecasting; in workshops with young scientists and engineers around the world; and in online games.
Here are the 12 that I came up with:
  1. Open Collaborative Research Proposals
  2. Communicating Science with Blogs
  3. Spontaneous Publication of Raw Research Data
  4. Routine Virtual Meetings in Second Life
  5. Empirical Investigation of Virtual World Properties
  6. Uploading of Spectra on ChemSpider
  7. Open Source Drug Discovery
  8. Automation of Crystallization by an Academic Group
  9. Robot Scientist Creates and Evaluates Microbiology Hypotheses
  10. Data Vizualization Group in Second Life
  11. InChIKey Web Services Facilitates Indexing of Molecules
  12. The X2 Project!

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Friday, May 02, 2008

Chemical Heritage Foundation Talk on Second Life

Earlier this week, I attended the LISE08 conference at the Chemical Heritage Foundation in Philadelphia. The theme this year was New Media and Technology in Science Education and I talked about using Second Life in the chemistry classroom.

David Shaffer gave a very entertaining and thoughtful presentation on epistemic games. These are games simulating complex systems like urban planning.

Tom Tritton reviewed the conference for CHF.

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