Tuesday, February 27, 2007

Chemistry Central Article on Open Chemistry

Matt Todd has another article on Open Science trends in chemistry. This one is in the Open Access journal Chemistry Central.

I found out about it from click-throughs to our UsefulChem wiki, which is listed as a reference. Nice to see the meshing of standard journal article and social software content. As we keep cross citing, it will become more and more difficult to distinguish and categorize knowledge sources.

Monday, February 26, 2007

The Semantic Chemist

I recently interviewed Robert Parker, Managing Director of RSC Publishing, you can read the interview in the February issue of chemistry news magazine Reactive Reports in which he discusses a new approach to the publication of scientific papers, RSC Prospect, and how it will benefit readers and the scientific community at large. It would be interesting to know what UsefulChem users think to the RSC's new approach to meta data and a semantic chemical web.

"We needed a meaningful way of identifying compounds uniquely and one that's machine readable—InChI fits the bill. Similarly, CML offers us a way of structuring lots of the science within a paper to both preserve the original science and do interesting things with it, and by demonstrating some of these applications, we hope to encourage wider adoption," Parker told me.

Tuesday, February 20, 2007

Crystalline Success

It looks like we have finally isolated one of the Ugi products we have been trying to make for a while. After analyzing the failed reactions and the kinetics of each step, we learned to stop using unstable aldehydes (like phenylacetaldehyde) and isonitriles (like 2-morpholinoethyl isonitrile).

It was then simply a question of mixing an amine (5-methylfurfurylamine) and aldehyde (piperonal) that we know cleanly form an imine in methanol then adding the carboxylic acid (boc-glycine) and isonitrile (t-butyl isonitrile) and waiting long enough to watch the crystals form.

Alicia was first (EXP052) to isolate and characterize her crystals by H NMR - see the assignment below. The tricky part was that one of the amide H's and the benzylic H were overlapping with the furan H's. Exchanging the amide H's with methanol-d4 made the assignment pretty clear.

Khalid is also getting crystals with another aldehyde and isonitrile and we should have an assignment for that Ugi product shortly as well. (EXP060)

On to boc deprotection and cyclization.....

Chemical Blogspace Tags




t-butyl isonitrile

Sunday, February 11, 2007

Molecules on Chemical Blogspace

Egon just alerted me to the new molecule displays on the Chemical Blogspace front page. Tagged molecules now show up in a special area and link back to the relevant blog posts and additional information about the substances.

This is a particularly elegant way to evolve a bit more towards a semantically aware chemical web because it requires so little from the author. Just add a few simple tags.

The UsefulChem group should recognize a few (all too) familiar molecules on the page, such as these:

2-morpholinoethyl isonitrile




Thursday, February 08, 2007

My Talks at Spring 07 ACS

The schedule for the American Chemical Society meeting in Chicago is finalized. There are some really great sessions on Web2.0 tools and chemistry.

Here are my talks - I hope to see some of you there!

PAPER TITLE; "Teaching organic chemistry with blogs and wikis" (final paper number: 25)
DIVISION: Division of Chemical Education
SESSION: Using Social Networking Tools to Teach Chemistry
DAY & TIME OF PRESENTATION: Sunday, 25 March 2007 from 11:15 AM to 11:35 AM
LOCATION: McCormick Place North, Room: Room N230B, Level 2

PAPER TITLE; "Open notebook chemistry using blogs and wikis" (final paper number: 1607)
DIVISION: Division of Chemical Education
SESSION: Communicating Chemistry
DAY & TIME OF PRESENTATION: Tuesday, 27 March 2007 from 9:45 AM to 10:05 AM
LOCATION: McCormick Place North, Room: Room N227B, Level 2

Tuesday, February 06, 2007

Making Anti-Malarials: Feb 2007 Update

In the spirit of Just Science Week, this might be a good time to take stock of where we are in the synthesis of our anti-malarial agents.

We are still attempting to make a series of diketopiperazines, predicted to inhibit enoyl reductase, an enzyme that the malaria parasite requires to build its cell wall. The synthesis should be straightforward, involving a Ugi condensation of an aldehyde, an amine, a boc-protected amino acid and an isonitrile, followed by simultaneous deprotection and cyclization in trifluoroacetic acid. (See here for a collection of relevant papers)

Most of the starting materials are commercially available. One of the key aldehydes, DOPAL (3,4-dihydroxyphenylacetaldehyde) was not available but we were able to make it in one step from adrenaline.

Before using DOPAL routinely, we sought to understand the reaction using cheap commercially available aldehydes. DOPAL bears phenolic groups and is a benzylic aldehyde. To simplify analysis of these factors we used phenylacetaldehyde, piperonal, 3,4-dihydroxybenzaldehyde and similar compounds.

Recently, we started using H and C NMR to monitor these reactions closely by carrying them out in NMR tubes. By exporting the NMR files in JCAMP format we were able to present these spectra in an interactive format on the web using JSpecView, giving anyone the ability to expand and overlay spectra at will. Handling all spectroscopic data in electronic format offered the further advantage of being able to apply automation to the analysis, such as the generation of kinetic data using VBA in Excel.

Although we have not yet isolated and fully characterized a Ugi product or diketopiperazine, we have reported all of our attempts in Open Notebook Science format. Some of the information from these experiments should be useful to other chemists attempting similar reactions.

The list of experiments carried out by my group related to the Ugi reaction can be found here.

Here are some of our key findings so far:

1) The formation of an imine with phenylacetaldehyde is very fast (at least 10/(M*min)) but is accompanied by side reactions that dominate the reaction. This suggests that similar problems may plague the benzylic aldehyde DOPAL.

2) Aromatic aldehydes such as piperonal and veratraldehyde react much more slowly than phenylacetaldehyde in the formation of an imine.

3) Imine formation is 14 times slower with t-butylamine compared with 5-methylfurfurylamine.

4) Imine formation is about 10 times faster in methanol compared with chloroform.

5) 2-morpholinoethylisocyanide is not a suitable component for a Ugi reaction because it decomposes in the presence of the carboxylic acid boc-glycine. This is unfortunate because, unlike most isocyanides, this one does not stink. We had to return to the commercially available benzyl isonitrile.

6) In the absence of the carboxylic acid component, the imine and benzyl isocyanide do not react.

These are the issues that we would like to resolve:

1) Sometimes, the imine reverts back to the aldehyde upon addition of the carboxylic acid boc-glycine. This can range from nearly complete reversal to just a small extent. James and Alicia are looking into this, including using molecular sieves to trap the water during imine formation.

2) Of course the key issue is: does the Ugi product form under optimal conditions using an aromatic aldehyde and benzyl isonitrile. We'll find out soon enough from Khalid's run with veratraldehyde, 5-methylfurfurylamine and boc-glycine. He got a precipitate after an overnight run...

3) Is a phenol compatible with the Ugi reaction? Sean is showing that the imine formation is accelerated using 3,4-dihydroxybenzaldehyde. It remains to be seen how it behaves with the rest of the components but we have reason to believe that it might be tolerated.

4) Will the Ugi product cyclize? The cyclization approach we are using is based on work using cyclohexenyl isocyanide, which is not commercially available at a reasonable price. It remains to be seen if this will work with benzyl or t-butyl isocyanide.


2-morpholinoethyl isonitrile






Friday, February 02, 2007

Batch Decompression of JCAMP files

I have developed a Java package to decompress NMR data taken from our Varian instrument and stored in JCAMP format. This software was adapted from Robert Lancashire's jspecview program, specifically the JDXCompressor.java and Coordinate.java classes. It reads a set of compressed JCAMP NMR files according to a configuration file with the following format:

<?xml version="1.0" encoding="utf-8" ?>

The program's output is a BLOCK JCAMP file, in this case output.jdx, containing the decompressed data from the input files. Right now only a few of the header fields are retained, those needed for reaction kinetics analysis using Excel VBA software (work in progress!).

In order to use, place all compressed jdx files in the same folder where all these files are located. Modify the configuration.xml file using Notepad to list the compressed files then double click on the run.bat file. The BLOCK file with the name output.jdx will be created. Note that this program just copies the titles in the original jdx files so make sure to put something meaningful in the TITLE parameter of the compressed files to keep track of them when using the Excel tool to calculate kinetics or JSpecView to visualize.

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