NMR Overlay with JSpecView

Click here to start an applet with an example of spectral overlay using JSpecView.

Robert Lancashire updated the code for JSpecView to fix the problem of faulty peak offset for NMR spectra in overlay mode. I have updated our server so that the new applets will be downloaded for UsefulChem applications. The new JAR files are available from Sourceforge.

It is hard to explain in words just how powerful this is for monitoring reactions and providing useful minable data in an Open Chemistry environment. So I made a recording to show how it can be used to monitor the formation of the imine in EXP045, the first step of the Ugi reaction. By using enough superimposed spectra from key points in the reaction, it is possible to resolve an ambiguous interpretation of an NMR showing only the final result.



The merging of spectra is accomplished easily by creating a BLOCK file from individual JCAMP files:
1) Create at txt file using Notepad and rename it filename.jdx
2) Add this header
##TITLE=IMINE FORMATION
##JCAMP-DX= 5.01
##DATA TYPE= LINK
3) Add this footer
##END= $$end of BLOCKs
4) In between the header and footer insert single JDX files by opening them in Notepad then copying and pasting. It is ok to leave space between the file blocks for clarity.
5) The first parameter of each file block is ##TITLE=. Put something meaningful there because this will be used by the overlay key to identify each spectrum by color.
6) Download this html file by right clicking and saving. Modify the 3 places in the file that call the JDX file to link to the one you just created.
7) Upload the JDX and HTML files to a server with the new JSpecView JAR files in the same folder.
8) Link to the HTML file to use JSpecView in overlay mode. Firefox tends to crash when going back and forth between applets and needs to be reloaded to fix that.

It is important that all spectra be zeroed on TMS properly. If a spectrum is off, use JSpecView to calculate how far off in Hertz (ppm * MHz of the NMR, in our case 300). To shift the spectrum to the left (downfield) subtract this correction factor from the number under the parameter REFERENCE_POINT= in the JDX file.

1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3
5-methylfurfurylamine

Communicating Chemistry at ACS

I just got the schedule for the symposium on Communicating Chemistry at the Spring 2007 American Chemical Society meeting in Chicago. It is being run by the Chemical Education (CHED) and Chemical Information (CINF) divisions. My talk on Open Notebook Chemistry using Blogs and Wikis is at 9:45 on March 27. It looks like there will be lots of interesting presenters and talks. Here is the schedule:

Communicating Chemistry — Part I — Tuesday, March 27

Cosponsored with CINF

L. Fine, Organizer

J. C. Kotz, Organizer, Presiding

8:30 — Introductory Remarks.

8:35 —1604. Pod casting and general chemistry: what is my chemistry professor doing in my iPod? H. D. Bapat

8:55 —1605. Hybrid learning as the bridge between technology and pedagogy in the first and second year chemistry curriculum. T. Poon, T. Morkin

9:15 —1606. Chemistry breaks the Top 100: Podcasting quantum mechanics. M. M. Francl

9:35 — Intermission.

9:45 —1607. Open notebook chemistry using blogs and wikis. J -C. Bradley, K. Mirza, J. Giammarco, A. Holsey, D. Strumfels, S. Gardner, L. Chen

10:05 —1608. What role do grades play in communicating chemistry? W. J. Vining

10:25 —1609. Improving the communication and efficiency in grading of laboratory reports. M. Hadley, J. R. Pribyl, J. A. Kaliski

10:45 — Intermission.

10:55 —1610. Enhancing communication in chemistry courses using DyKnowTM. B. L. Gourley

11:15 —1611. Taking ownership of learning:Can adding technology to the traditional classroom increase the opportunity for students to be more responsible for their own learning? C. M. Turner

11:35 —1612. E-learning chemistry. J. Reeves, J. Tyrell

Communicating Chemistry — Part II — Tuesday, March 27

Cosponsored with CINF

J. C. Kotz, Organizer

L. Fine, Organizer, Presiding

1:30 — Introductory Remarks.

1:35 —1651. Visualizing acid/base chemistry: Using electostatic potential surfaces to teach acid/base strengths. R. W. Morrison, R. Hubbard IV, K. Soncha

1:55 —1652. Open access peer reviewed portal for communicating chemistry: Analytical Sciences Digital Library. H. A. Bullen

2:15 —1653. Comparison of student discourse in online and face-to-face environments. G. C. Weaver, K. F. Green

2:35 — Intermission.

2:45 —1654. Chemical Eye on ears tuned to public radio. P. J. MacDougall

3:05 —1655. Science Outreach in the City of Chicago. M. C. Lach, M. Davis

3:25 —1656. "Smart Cities": Summer science in the mean streets of France. G. P. Niccolai

3:45 — Intermission.

3:55 —1657. Collaborative efforts by Illinois local American Chemical Society sections to promote chemistry at the Illinois state fair. H. D. Bapat

4:15 —1658. Analysis of how scientists explain their research and parallels to how science teachers explain science. H. Sevian, L. Gonsalves

4:35 —1659. Service-learning with a general chemistry lab: Communicating chemistry through application. M. J. Harvey

Communicating Chemistry — Part III — Wednesday, March 28

Cosponsored with CINF

L. Fine, Organizer

J. C. Kotz, Organizer, Presiding

8:30 — Introductory Remarks.

8:35 —1698. Teaching chemical information: Tips and techniques from the Division of Chemical Information Education Committee. S. Cardinal, S. Yu

8:55 —1699. Communicating the chemistry behind issues. B. Venkataraman

9:15 —1700. Teaching chemistry majors to write like chemists. M. S. Robinson, F. L. Stoller

9:35 — Intermission.

9:45 —1701. Investigational writing exercises to complement undergraduate biochemistry experiments. P. J. Higgins

10:05 —1702. Readability levels of college chemistry textbooks from introductory chemistry to physical chemistry. E. A. Drommerhausen, J. R. Pribyl

10:25 —1703. Student opinions of writing assignments in organic chemistry courses for majors. D. P. Cartrette

10:45 — Intermission.

10:55 —1704. How to think logically about organic chemistry. E. T. Papish

11:15 —1705. Communicating the concepts of resonance and conjugation. J. J. Mullins

11:35 —1706. Use of humor and illustrations in organic chemistry lectures. V. Dragojlovic

Imine Understanding

As can be seen from most of the recent changes on the UsefulChem wiki, Khalid, Alicia and James have been uploading a lot of NMRs in JCAMP format. These have mainly been variations of the basic experimental design of closely monitoring the course of the Ugi reaction by stepwise addition of reagents.

There are many advantages to carrying out Open Chemistry in this format. First, any observations and conclusions that we make can be verified in detail by anyone. Second, many unstated assumptions generally part of the traditional publication process in organic chemistry, such as the purity of the starting materials or the ability of a researcher to read a spectrum without error, can be interrogated independently. Third, there is a wealth of information available to be mined for other investigations beyond the scope of our project. For example, the presence and kinetics of side reactions can be explored by other researchers without having to repeat the experiment. This philosophy or re-purposing and mining experimental results is common in bioinformatics but has not yet caught on in chemistry, especially organic chemistry.

Although our analysis is not complete, we have uncovered some important information relating to the formation of the imine, which is the first step of the Ugi reaction:

1) Phenylacetaldehyde does not react cleanly with a primary amine, such as t-butylamine in CDCl3 and presumably methanol as well. This suggest that other benzylic aldehydes, such as DOPAL, may not react cleanly either and this has important consequences for our synthetic strategy. There have been published attempts of the creating of an imine between phenylacetaldehyde and t-butylamine (Verhe 1980) in CCl4. However, closer inspection of that article reveals that the imine was not characterized and used as a crude product in a subsequent step. If NMR monitoring of this reaction had been made available to the community, it would have saved us (and many others working on other projects I am sure) a lot of time.

2) Aromatic aldehydes such as piperonal and veratraldehyde react cleanly, although more slowly, with the primary amine 5-methylfurfurylamine. Furthermore the equilibrium (at least in CDCl3) appears to be shifted sufficiently towards the imine, making removal of the water a non-issue in optimizing this reaction. Thus we will use aromatic aldehydes to complete the characterization of a Ugi reaction by NMR monitoring before attempting to modify conditions for benzylic aldehydes (needed for many of our targets). We also have enough data to report second order kinetic rates, which we will report on shortly in the relevant experiments.

Although the use of JSpecView is considerably more convenient than paper (e.g. unlimited peak magnifications), there are still some issues. Firefox tends to crash after intensive use going back and forth between spectra, usually after about 20 times. This is always easily corrected by killing and restarting the browser. Also, it is possible to superimpose spectra using BLOCK files in JSpecView and I will post on this as soon as a final glitch has been worked out (the reference position is ignored and spectra appear about 1.6 ppm off). Robert Lancashire has told me he will try to fix this in the coming week and I appreciate his help so far, especially on Christmas day :)

Remote Controlled Labs

An interesting story on Chemistry World caught my attention this morning:

A remote-controlled chemical laboratory that can be operated through the internet was unveiled on 8 December at Cambridge University, UK.

Part of the unique educational ‘Weblabs’ project, already trialled at the universities of Cambridge, Birmingham and Imperial College, UK, and the Massachusetts Institute of Technology (MIT), US, the system allows chemical engineering students anywhere in the world to operate a real-life laboratory without costly equipment.

As best as I can tell from the website, this is reserved for enrolled students and only for doing pre-defined experiments.

But at some point I view our UsefulChem project and other Open Science initiatives to evolve to include a physical component, where anyone (or any intelligent system) can carry out novel experiments to extend knowledge.

There is actually a mechanism to (sort of) do this now on the UsefulChem wiki: the Experimental Plans page. Anyone is welcome to propose a detailed experimental plan to advance our research objectives, now primarily on the synthesis of anti-malarial agents. If it makes sense, I'll discuss it with my research group and allocate resources to execute it. I don't care if it comes from a Nobel laureate, a precocious 14 year old or a bot.


Taken from Weblabs page.

Flu Target

We have not talked much about the flu on UsefulChem but this article might be of interest since there is a real target to think about. A next step would be to obtain the pdb file and start to look at docking. From Chemistry World:

Structure of key influenza A protein revealed

06 December 2006

The crystal structure of a molecule important for the replication of the influenza A virus has been solved, report US researchers. Now that scientists know what the protein looks like they can design drugs that block its action and prevent viral spread through the body.