NMR prediction on ChemSpider

As Tony recently mentioned, there is a new button on ChemSpider to predict H NMR spectra based on the nmrdb.org 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.

Tag: InChIKey: PBZQTKRWYXTXIS-WLRTZDKTBU

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.

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.

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.

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:

http://tinyurl.com/4multu

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.

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.

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

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

Interview with Jean-Claude Bradley, Associate Professor of Chemistry and E-Learning Coordinator, College of Arts and Sciences, Drexel University

• Drexel CoAS E-Learning Blog
• Drexel CoAS E-Learning Podcast
• Drexel Island on Second Life

• Open Notebook Science using Blogs and Wikis
• Teaching Chemistry with Second Life
• Other topics and tools mentioned:
• Audacity - free audio editing tool
• Blogger - free blog service
• Camtasia Studio - screen recorder
• Creative Commons - licenses for authors, artists, and educators
• Feedburner - manage RSS feeds and track subscribers
• Second Life - a 3D virtual world
• SMILES - for describing chemical molecules
• WikiSpaces - free Wiki service

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!

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.

UsefulChem on ChemSpider

As Antony Williams mentions in his blog, UsefulChem molecules now have their own url on ChemSpider:
http://usefulchem.chemspider.com

This is important on so many levels. I've been talking about using ChemSpider as an integral part of our research for some time now and we've been steadily migrating content as new functionalities became available. We still have a lot to do to complete the process but the path is clear.

The ability to upload spectra of all types (IR, H NMR, C NMR, MS, etc) in JCAMP-DX format allows for anyone with a browser to drill down to any desired expansion using JSpecView. It just makes sense to upload the NMRs of our starting materials and our fully characterized products so that we can always be just a click away from the online lab notebook when discussing our chemistry.

The value of being able do substructure searching for our compounds is immense. Most organic chemistry students are not interested in learning how to run and maintain software on a lab server to keep track of their molecules. They also don't want to learn SMARTS. ChemSpider has a very familiar graphic interface for drawing molecule fragments to do substructure searching. For a free and hosted solution, the energy of activation for using ChemSpider has become very low indeed, especially for Open Notebook Science applications.

As we approach 200 experiments it is becoming clear that the ability to retrieve information is just as important as doing the experiments. Systematic tagging of experiment pages with InChIKeys and InChIs is a simple way to automatically allow for direct links from ChemSpider to UsefulChem pages via Google.

We've come a long way from using a blog to track our molecules :)

Scholar2Scholar Webcast and Report

The webcast from the Scholar2Scholar conference on April 16, 2008 is now available here. The general introductions start at 15:30, my intro by Jane Bryan starts at 19:08, my talk on "Enhancing Scientific Communication through Open Notebook Science" at 23:28 and the panel at 51:40 (after several minutes of dead audio unfortunately).

The panel consisted of Jean-Claude Bradley, Andre Brown, Nicole Engard, James Mitchell, Banu Onaral, Beth Ritter-Guth, and Scott Warnock.

Small round-table discussions followed and were diligently documented by the library folks. Their notes will be posted here on the wiki.

Overall it was a very well organized and productive event. I was impressed by the level of engagement by the participants at my round table and I expect future projects to evolve from these discussions.

I especially thank Jay Bhatt and Anita Chiodo for setting the process in motion a few months ago!

Cell Article on Open Drug Discovery

Seema Singh wrote a review "India Takes an Open Source Approach to Drug Discovery" which just appeared in Cell: Volume 133, Issue 2, 18 April 2008, Pages 201-203. (The doi doesn't work yet but try this link in the meantime). You'll need a subscription to view it, an increasingly familiar irony of much of the Open Science discussion these days.

UsefulChem and our collaborators got a nice mention:

A related initiative is UsefulChem (http://usefulchem.wikispaces.com/), set up by Drexel University chemist Jean-Claude Bradley. Bradley has pioneered Open Notebook Science in which lab notebooks and raw research data are posted on the web for anyone to see and respond to (http://usefulchem.wikispaces.com/All+Reactions). As for success, Bradley says, “Probably the best example of a positive outcome from UsefulChem is finding two compounds that are somewhat active against malaria [in vitro],” blocking the activity of falcipain-2, a Plasmodium falciparum cysteine protease. “This demonstrates that a team of researchers can work together in the open—Rajarshi Guha from Indiana University did the docking calculations, my group at Drexel did the syntheses and Phil Rosenthal's group at UCSF did the testing.”

NMR viewer in Second Life

Andrew Lang just finished coding this nifty little JCAMP-DX viewer in Second Life. The video shows that you can expand any area of the spectrum by typing zoom followed by the desired range in the chat box.

You can also type "back" and "reset" commands. It essentially functions like Robert Lancashire's JSpecView if it were running in Second Life (although integration is not yet implemented).

There are still a few kinks to iron out but it should work with any spectrum that can be represented in JCAMP-DX format: IR, CNMR, HNMR, UV-vis, MS, etc.

This should extend considerably the set of tools available to chemistry teachers who use Second Life to interact with students.

Give it a try on Second Nature island: SLURL. (You'll need the most recent version of Second Life to run this and click the link from within IE, not Firefox)

Scholar2Scholar Tomorrow

The Scholar2Scholar conference is upon us. Jay Bhatt and Anita Chiodo did an amazing job with organizing this from the start. I'll be giving the introductory talk on "Enhancing Scientific Communication through Open Notebook Science". Here are the slides - I'm starting with an introduction to Web2.0 using FriendFeed as an example.

| View | Upload your own

date: April 16, 2008 8:30-1:30
location: Drexel University Bossone Lobby

Join us to discuss how Web2.0 is changing scholarship. Dr. Jean-Claude Bradley will give a presentation, followed by a panel discussion featuring: Andre Brown, Nicole Engard, James Mitchell, Banu Onaral, Beth Ritter-Guth, and Scott Warnock. Small round-table discussions will follow. An optional Dutch-treat lunch concludes the day.

Back from Spring08 ACS

The American Chemical Society meeting in New Orleans proved to be as hectic as usual. I didn't get to spend as much time with everyone I was hoping to touch base with but I did get some useful things done:

1) I presented on the use of Cheminformatics in Open Notebook Science and Teaching Chemistry with Second Life. Since the ACS oral sessions are so short (15-20 mins before questions) this is a good opportunity to get our work recorded in a concise format. Speakers like to complain that they need a full hour to do justice to their elaborate projects but the shorter format seems to match the attention span of most attendees.

2) The Sci-Mix session on Monday was very hectic. I presented two posters related to my talks and helped out with the opening of the poster session on ACS island. We had 20 posters in Second Life and it was great to finally meet a few of the presenters and the organizer Kate Sellar (Finola Graves) in person. Kate was running Second Life on a large screen right at the poster entrance and giving out t-shirts. Andy Lang (Hiro Sheridan) was also helping out remotely from within Second Life. By all accounts it was well received. The posters will remain up on ACS island for the next few months and it will be possible to contact presenters via bells next to their posters.

3) I also finally met several people that I have known only virtually for some time: Rajarshi Guha, David Wild, Rich Apodaca, Noel O'Boyle and Warren DeLano. Rajarshi, Rich, Noel, Warren, Geoff Hutchison and I went out for the Blue Obelisk dinner on Tuesday night.

4) I had a good brainstorming session with Rajarshi about representing experimental workflows in XML. He suggested using Taverna to create "null" workflows - since our lab experiments are physical rather than executing code. Noel suggested using Knime. The idea is to represent experimental steps leading to a result in a standard machine readable (and thus minable) format. We're going to start very simply by limiting the workflow space to Ugi reactions.

Attila Csordas writing his thesis on a blog

Attila is writing his thesis openly and is welcoming comments:

From now on I start every “thesis live” post with the standard introduction: In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential

I am not aiming any perfection, my focus is clearly on getting things (the PhD) done here. Anyway, I found the idea of “writing” a complete, lengthy and formal thesis outdated and inefficient (after all, scientists should conduct nice experiments and publish their results in short, inforich and accessible research papers in order to share it ASAP with the research community, not in book-length, otherwise unaccessible PDFs) and so I try to keep myself motivated by

- doing this “thesis live” series as an open science experiment and getting useful feedback from my fellow scientists and readers

- trying to include as many systemic, whole body level material into it that could be relevant for systemic regmed approaches

- reminding myself every day that without a PhD it is hard to move further in science officially (that’s the least motivating factor though as it is official)

Data-Centric eScience Workshop Call for Papers

General Info: Call for Papers for the UK e-Science AHM2008

=================================================

'Crossing Boundaries: Computational Science, E-Science and Global

E-Infrastructures'

8th - 11th September 2008 in Edinburgh, Scotland

Call for workshop papers for the workshop on

The Global Data Centric View of e-Science or “Data in Science, Arts and Medicine: getting it, testing it, using it, keeping it, and sharing it!”

Abstract Submission (Abstracts due 1 May)

========================================================

Further details about the workshops and important information about the submission and review process, including guidelines for authors can be found at: http://www.allhands.org.uk/2008/programme/call.cfm

Submission Deadline: 1st May 2008

Enquiries: Please address any enquiries about abstract submission to

admin@allhands.org.uk

=======================================================

General Information:

This is the principal e-Science meeting in the UK and brings together researchers from all disciplines, computer scientists and developers to meet and exchange ideas. The meeting is in its seventh year and normally attracts between 500 and 600 participants. The theme for this year's meeting is 'Crossing Boundaries: Computational Science, E-Science and Global E-Infrastructures'. The appointment of Professor Peter Coveney (UCL) as Programme Chair, heralds a new approach. This year, for the first time, key papers will be published in two back to back editions of Philosophical Transactions of the Royal Society A in the early part of 2009, with the title 'Crossing Boundaries: Computational Science, E-Science and Global E-Infrastructures'. One of the central aims of this year's meeting is to promote the domain specific applications aspects of e-Science, as well as building bridges between the three communities of the theme title.

The general format of the meeting will include cross-community symposia (kicked off by invited key speakers) and workshops. The workshops are being championed by Programme Committee members in what are considered to be key areas of e-Science that need to be addressed, rather than by a call for workshops as has been done in the past. There will also be opportunities to present 20 minute talks.

Call for workshop papers for the workshop on

The Global Data Centric View of e-Science or “Data in Science, Arts and Medicine: getting it, testing it, using it, keeping it, and sharing it!”

Organisers:

Workshop Organizer - Jeremy Frey, School of Chemistry, University of Southampton

Workshop Programme Committee

Roger Barga, Microsoft Research, Redmond, USA

Colin Bird, IBM Labs, Hursley, UK

Jean-Claude Bradley, Department of Chemistry, Drexel University, USA

Simon Coles, University of Southampton, UK

Peter Dew, School of Computer Science, Leeds, UK

Lee Dirks, Microsoft Research, Redmond, USA

Jon Essex, University of Southampton, UK

Geoffrey Fox, Indiana, USA

Lee Giles, Penn State, USA

Jane Hunter, University of Queensland, Australia

Charles Laughton, Nottingham, UK

Liz Lyon, UKOLN, Bath,

Peter Murray-Rust, Unilever Centre, Cambridge, UK

Jim Myers, NSCA, Illinois, USA

Cameron Neylon, RAL, STFC, UK

Mike Pilling, School of Chemistry, Leeds, UK

Peter Turner, University of Sydney, Australia

Andrew Woolf, RAL, STFC, UK

Invited talks: TBA

Description of workshop:

The WWW highlights the globally distributed nature of production and use of research data. This global nature may arise from the intrinsic nature of the data (i.e. global environmental data) or the global scope of the production (e.g. the existence of small-scale laboratory data producing data in almost all countries), or the dissemination of data collected centrally to the worldwide community (e.g. Central Facilities, LHC). The idea of ‘Follow the Data’ is one way to look at and unify the impact of e-Science, Cyber-infrastructure and the Grid on research in the Sciences, Arts and Medicine.

Call for papers:

In this workshop we request papers (abstracts) contributing to the consistent or integrated treatment of data derived from laboratory processes, computational simulations, analyses, legacy systems and human annotation and that address one or more of the following:

• Distributed Data Acquisition & Generation
• Data Management, Migration and Curation
• Data Models, Representations,
• Metadata and Annotation
• Data Flows & Access Services
• Data Translation, Normalization and Integration
• Data Evaluation, Error correction and Attribution of confidence
• Data transparency: Approaches and Policies
• Data Search, Open Data

We are particularly interested in papers that highlight and demonstrate the ways in which the data centric view provides a unifying approach to the handling and processing of information in multi- and interdisciplinary environments in ways that can satisfy the needs of small, medium and large-scale generators and consumers of data and for example the role of Web 2.0 and the “Cloud” in dealing with the topics listed.

Workshop Discussions

We are planning a blog/wiki/forum operation at the workshop so that the questions & discussion can be captured and 'published' along with the papers (a bit like Faraday Discussions for those who know the Royal Society Chemistry system). We should be able to do this in an efficient way making use of the fact that most people in the w/s will have a laptop open and be typing anyway!

Further details about the workshops and important information about the submission and review process, including guidelines for authors can be found at: http://www.allhands.org.uk/2008/programme/call.cfm

Submission Deadline: 1st May 2008

Ugi Precipitation Predictions

Following a recent discussion about the Ugi Master Table, things got sorted out enough that Rajarshi has built a model to predict which of the top 100 molecules from his docking run against falcipain-2 (V2 receptor) are most likely to precipitate the Ugi product. He get 6 hits, 3 of which are part of the training set and 3 have not yet been attempted yet. The new ones are here:

Hit 87

Hit 83

Hit 72

As we get more information in the table, we can start formulating new hypotheses. One of the factors that I have suspected for a while is that the products that precipitated tended to come from less concentrated solutions. Now we are starting to get results from the same Ugi reactions at different concentrations, where this effect should be more obvious.

For example this compound precipitated from a 1 mmol scale reaction with 4 ml of methanol but remained in solution at a 0.25 mmol scale with 0.25 ml of methanol.

This seems counterintuitive because one would expect increasing the concentration should make it easier to precipitate. But I think those solutions are so concentrated that the reagents compete as role of solvent with methanol.

Rajarshi has not yet taken into account the role of concentration but we have discussed it and can more easily do so as we accumulate more results.

ACS Island Party Tonight

As I mentioned previously, the American Chemical Society is gearing up for a poster session in Second Life on April 7, 2008 immediately following the New Orleans ACS meeting Sci-Mix session at 20:00 EDT. There are currently 16 presenters from diverse chemical fields.

In anticipation of this event there will be a little party on ACS island tonight (April 2) at 18:00 EDT. Everyone is welcome to attend.

Just type "ACS" in the Second Life map search function to find the island.

We're Gonna Ugi All Night!

Thus begins the CHEM254 lab manual for the week of April 7, 2008 at Dominican University:

“Ugi to the left, Ugi to the right. This is so fun, we’re gonna Ugi all night.”

As I discussed a few days ago, Brent has followed through in a big way in incorporating the UsefulChem project into his teaching lab:

This experiment represents the beginning of collaboration with the UsefulChem Bradley open notebook science group of graduate and undergraduate research at Drexel University. The goal of the UsefulChem project is to use the Ugi 4 component reaction to synthesize possible anti-malarial compounds. Open notebook science allows immediate dissemination of experimental results that invites advice and suggestions as well as complementary experiments that enhance and advance the project. We are going to reproduce some of the Drexel results as well as perform two complementary reactions that have not been done at Drexel.

The procedure is derived from our lab notebook with one interesting vortexing modification :)

Part I.
Add 0.33 g of your aldehyde to 8 mL methanol in a 20 mL scintillation vial.
Screw on a Teflon (green) cap on the vial. Vortex to mix and dissolve the aldehyde.
Add 1 mL of methylamine solution to the vial.
Vortex to mix. Sing the “Ugi song” while vortexing.
Obtain 0.34 g of the carboxylic acid. Add the carboxylic acid to the vial.
Vortex to mix.
Obtain 0.39 g of tosylmethylisocyanide. Add the tosylmethylisocyanide to the vial.
Vortex to mix.
Take a photo of your reaction mixture.
Label the vial and let the reaction mixture sit in the sealed vial.

By taking pictures his students can directly compare the progress of the reaction with our group. The questions for this lab are also excellent and may result in some useful ideas for my students to ponder (this may end up being a realistic way to foster chemistry crowdsourcing):

What could you do to isolate your product if after 7 days if there are no spontaneously formed crystals?

Refer to UsefulChem Experiment 171 . Which reaction most closely corresponds to our experiment? What were the results?

Consider the IR spectrum may reveal that there is unreacted isocyanide in your product mixture. Where does the isonitrile group appear in an IR spectrum? (Refer to appendix 2B in your textbook.)

Consider the possible 1H spectrum of your Ugi product. How many aromatic Hydrogens are there? How many methyl groups are there? Where would you expect to observe the methyl groups?

Consider the possible 13C spectrum of your Ugi product. How many aromatic Carbons are there? How many carbonyl carbons are there? How many methyl carbons are there? Where would you expect to observe the methyl carbons?

If you were given four different compounds for each type of Ugi reactant (16 compounds in all), how many different Ugi products could you attempt to make?

Safety Question: What is the safest way to transfer 1 mL of 2.0 M methamine in methanol from the stock bottle to your reaction vial? Give a reasonable explanation of your choice.

I also really like that he is exposing his students to some handy cheminformatics tools:

Look up “tosylmethyl isocyanide” in chemspider. What is the InChI code? What is an InChI code?

Since Brent and I started the discussion we have a few more precipitates involving the non-stinky tosylmethylisocyanide that may be suitable for his lab. Khalid has been doing some tedious but very necessary data checking and recording and the updated results are available on the Master Table of Ugi reactions.

There are currently 65 reactions, with 20 giving precipitates - and we are now including reactions where the starting materials fail to dissolve. Not all the precipitates have been characterized but they will be over time. In fact the Ugi product that Brent is trying to make in his lab for next week has not yet been fully characterized - all those phenolic groups seem to give rise to solubility issues in CDCl3.

That is a risk associated with using Open Notebook Science for a teaching lab. But it is also one that could pay off because his students could be contributing valuable results to an ongoing research project focussed on making anti-malarial compounds.

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.

Tags
171H InChIKey XRHVBZVCUGMHPN-UHFFFAOYAR
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

NFAIS 2008 Sunday afternoon

Yesterday afternoon I attended the NFAIS conference in downtown Philadelphia. The talks were actually very engaging.

First up was David Weinburger, who co-wrote the "Cluetrain Manifesto", an enjoyable book that I caught on audio book a few years back. His talk was mainly about his new book "Everything is Miscellaneous", which looks interesting based on his talk. His main point was that hierarchical classification systems are not as useful for many systems compared with spontaneous tagging by online communities. He also indicated that information overload was not as big of a problem as many people suggest, something that I definitely think is the case in science.

Lee Rainie's presentation was also well done. He presented the results of the Pew Internet & American Life project. I thought the most interesting portion was at the end, where he described the 10 different types of people, classified according to their attitude towards technology. Hopefully his report will be available shortly along with the rest. (In the meantime, Bryan Alexander took some good notes on this session.)

I presented at the next session on "The Emerging Culture of the New Information Order" on Open Notebook Science, which was a good fit, giving a laboratory researcher's perspective of Web 2.0.

My co-panelists included Chris Willis from Footnote.com and Bryan Alexander from NITLE. Chris gave many good examples of the power of community tagging, including a new project bringing relatives of Vietnam veterans together on a massive digital "wall". Bryan also gave a stimulating talk but he was so addicted to his social software that he was recording video blog posts as we were waiting to speak :)

Scholar 2 Scholar Meeting at Drexel

I am co-organizing the Scholar 2 Scholar conference with Jay Bhatt and Anita Chiodo on the morning of April 16, 2008 at Drexel University in Philadelphia. Anyone wishing to attend add your name to the participant list on the wiki.

Drexel University Libraries’ Scholarly Communication Symposium
Scholar 2 Scholar: How Web 2.0 is Changing Scholarly Communication as We Know It
Web 2.0 technologies are more than just web-based games and social networks; these virtual environments are building communities of thought and practice which have very real implications for education and research in academia. How do educators, administrators, and librarians use or repurpose these tools to their advantage? What are the implications for teaching and research? Is the return on our investment of time and energy worth the engagement? How well do students learn through these collaborative avenues? What are the true benefits for scientific research? What are the potential conflicts or roadblocks? We will explore these questions and many more.

Open Medicine Editorial on Open Science

The Journal "Open Medicine" has published a very thoughtful editorial on "Open science, open access and open source software at Open Medicine" by Sally Murray, Stephen Choi, John Hoey, Claire Kendall, James Maskalyk and Anita Palepu.

Not only are they writing about it but they want to get their hands dirty as well:

Open Medicine is an open access journal because we believe that free and timely access to research results allows scientific knowledge to be used by all those who need it, not just those who can afford expensive journal subscriptions or user fees for individual articles. But is access to the final polished version of research enough? Could we do more to en­courage the collaborative reuse and reanalysis of existing data, or the verification of analyses? Could we move from open access to open science?

ACS Island on Second Life

The American Chemical Society will be offering a virtual poster session in Second Life from selected posters at the Sci-Mix session taking place April 6, 2008 at the next national meeting in New Orleans.

I'm helping out with that effort and I'm pleased to say that we have our first submission from Jodye Selco, Mary Bruno and Sue Chan: "Safe and economical chemistry inquiry for the K-12 classroom".


ACS island has the same shape as its logo of a phoenix, thanks to the skilled hand of Eloise Pasteur who carved out the Drexel island's dragon shape. The posters will be placed on the right wing, next to a "chemistry museum" area, also under development.


ACS island is currently open to everyone - feel free to stop by and explore as we develop the area (Andrew Lang, Hiro Sheridan in SL is also on the project). Gus Rosania has been a very active "resident scientist" - you can see his activities on drug transport near the middle.

Kate Sellar (Finola Graves in SL), who spearheaded this initiative at ACS, has just started a blog where she will chronicle activities on the island.

The easiest way to find the island is to type ACS in the Map search box in Second Life.

Open Notebook Science News - Barton and Rosania

Michael Barton has posted a brief essay on Open Notebook Science on his research web site:

As you might expect from the name, Open Notebook Science (ONS) has similarities with Open Source Software. The clearest likeness between the two, is the belief that by sharing and collaborating, more can be achieved than through secrecy and competition. An open approach to software development is proven to be successful: the greatest achievement is the development, and increasing adoption of the Linux operating system. On this foundation other applications like the Apache web server, MySQL database, and the PHP scripting language have been built, and the combination of the four is the engine running many websites, including this one. If ONS can enjoy a fraction of the success open software does, then science can only benefit.

He also discusses ONS on the February 2008 edition of Bio::Blogs.

In terms of an amazing example of recent ONS implementation, take a look at Gus Rosania's 1CellPK wiki. He currently has 9 of his group members with notebooks and he is trying to make the activities in his lab as transparent as possible. Obviously this involves experiments but also group meetings and his meetings with colleagues. He has also been providing detailed descriptions, including background and literature reviews, of his group's projects.

Of particular interest to my group is the description of our collaboration on new anti-malarial agents. Since we can track their activities and they can track ours in close to real time, it will be interesting to see if we can crack open all the black boxes of collaboration.

I have heard the objection many times that there is not enough time for researchers to read each other's lab notebooks. That's absolutely true but that is not an effective way to use these resources. The point is to spend little time skimming content and as much time as required drilling down to details when a relevant post is discovered. With Wikispaces one can also just subscribe by email or RSS feed to edits of a particular page. I would expect the UsefulChem group members to at least subscribe to the malaria project page I mentioned above.

Gus is also looking at displaying experimental results in Second Life and has been doing actual experiments on the physics of Second Life. See his blog for the chronicles of that adventure.