Ryan's Blog on NMR Software

Looking for a Great Weekend Read?

In fact, to borrow a phrase from a colleague, this might be the defacto article on Computer Assisted Structure Elucidation (CASE) for the next decade!

This article written by Mikhail Elyashberg, Antony Williams, and Gary Martin spans across two issues of the review journal, Progress in Nuclear Magnetic Resonance Spectroscopy. 

This article entitled, entitled, "Computer-Assisted Structure Verification and Elucidation Tools in NMR-based Structure Elucidation" is available online and you can review a preview of the content at:

http://dx.doi.org/10.1016/j.pnmrs.2007.04.003

This is a very important and comprehensive review of modern expert CASE systems over many years. It includes specific examples of complex natural product structures that have been automatically elucidated using such systems.

I thank the authors of this publication for their contributions in this area, and the efforts they have now put forth to communicate this story to the scientific community.

Please obtain a copy for yourself, I can promise that it is a very informational and intriguing read for those of you who do NMR regularly.

Automated Structure Verification by 1H NMR Only

I've blogged several times about the progress and applications of automated structure verification with the help of ACD/Labs software.

There are really two main approaches right now:

1. Combined verification which includes automatically verifying the correspondence between a proposed chemical structure and the 1D ¹H and 2D HSQC spectra. I've blogged about the publications and applications of this method previously.
2. ¹H only verification. Of course the first approach is preferable from an accuracy standpoint as the additional information gained from the HSQC spectrum increases the selectivity and specificity of the results.

However, I always get questions on how well we perform on ¹H NMR only because in some organizations and environments it is simply not feasible to always run an HSQC in tandem with a routine ¹H NMR analysis.

As mentioned in previous posts, we've already conducted a validation study on this approach and it was published in a 2006 article in MRC. We've continued to investigate and validate this approach and we recently presented our latest results using 1D ¹H NMR data only at ENC 2008.

The poster highlighted a study on the automatic evaluation of over 15,000 Aldrich compounds and spectra from Aldrich NMR Spectra Database.

The results of this study revealed that the software was able to confirm 88%of all spectra as consistent and flagged less than 5% as inconsistent.

One of the more interesting discoveries in this study was that it revealed some truly wrong structures in the Aldrich NMR database.

More information on these as well as shortcomings in prediction, processing, and analysis are provided in the poster that can be downloaded:

http://www.acdlabs.com/download/publ/2008/enc08_aldrich.pdf

Using NMR for Quantitative Analysis

Do you currently use NMR for quantitative analysis?

At the University of Ottawa NMR Facility Blog, Glenn Facey provides some acquisition tips for ¹H NMR spectra.

If you perform quantitative analysis on your spectra, how do you do it? Do you do it manually by hand, or do you use some software to help?

I am not sure how many of you are aware of Quanalyst, a quantitation tool available in ACD/1D and 2D NMR Processor that can measure different spectral attributes and automatically measure the result.

For example, some common applications of the tool are to:

• Calculate the ratio of components in a sample mixture. ( I think this application is especially useful for those in the chemical industry)

• Reaction Monitoring

• Finding and quantifying a multiplet for a specific atom

• Quantifying coupling constant changes in a specific multiplet across a series of spectrum

Here are a couple of application notes available that describe a few of the different applications of Quanalyst:

Reaction Monitoring with Quanalyst (PDF)

Optimizing the Process of Quantifying: From Manual to High-Throughput (PDF)

I will also provide you with a link to an old movie on Quanalyst from an older version of ACD/1D NMR Processor that I still think will give you an idea of how Quanlyst works. Note, if you can't view the movie, you can download it here.

Perhaps it's time for a new version of this movie!...I'll try to get to that and share it with you.

In the meantime, if you are currently doing quantitative analysis, I invite you to share your thoughts, insights, workflows, etc. in the comments section.

Download a Trial of ACD/1D NMR Assistant!-Expired

This offer is now expired.

More on Indirect Covariance

Gary Martin has added a comment to an earlier post I wrote on Indirect Covariance and was kind enough to post an updated publication list on this topic. I have simply copy and pasted his comments in this post to provide more exposure to his list:

Ryan, it has been a while since you updated the publication list on indirect covariance methods, so I thought it appropriate to do that with a post:

F. Zhang and R. Bruschweiler, J. Am. Chem. Soc., 126, 13180 (2004).

K. A. Blinov, N. I. Larin, M. P. Kvasha, A. Moser, A. J. Williams, and G. E. Martin, Magn. Reson. Chem., 43, 999 (2005).

K. A. Blinov, N. I. Larin, A. J. Williams, M. Zell, and G. E. Martin, Magn. Reson. Chem., 44, 107 (2006).

K. A. Blinov, N. I. Larin, A. J. Williams, K. A. Mills, and G. E. Martin, J. Heterocyclic Chem., 43, 163 (2006).

K. A. Blinov, A. J. Williams, B. D. Hilton, P. A. Irish, and G. E. Martin, Magn. Reson. Chem., 45 544 (2007).

W. Schoefberger, V. Smrečki, D. Vikić-Topić, and N. Müller, Magn. Reson. Chem., 45, 583 (2007).

G.E. Martin, P. A. Irish, B. D. Hilton, K. A. Blinov, and A. J. Williams, Magn. Reson. Chem., 45, 624 (2007).

G.E. Martin, B.D. Hilton, P.A. Irish, K.A. Blinov, and A.J. Williams, J. Heterocyclic Chem., 44, 1219 (2007).

G.E. Martin, B.D. Hilton, P.A. Irish, K.A. Blinov, and A.J. Williams, J. Nat. Prod., 70, 1393 (2007).

G.E. Martin, P. A. Irish, B. D. Hilton, K. A. Blinov, and A. J. Williams, Magn. Reson. Chem., 45, 883 (2007).

B. Hu, J.-P. Amourex, and J. Trebose, Solid State Nuclear Magnetic Resonance, 31, 163 (2007).

G.E. Martin, B.D. Hilton, P.A. Irish, K.A. Blinov, and A.J. Williams, J. Nat. Prod., 70, 1966 (2007).

D. A. Snyder, Y. Xu, D. Yang, and R. Bruschweiler, J. Am. Chem. Soc., 129, 14126 (2007).

G.E. Martin, B. D. Hilton, K. A. Blinov, and A. J. Williams, Magn. Reson. Chem., 46, 138 (2008).

G.E. Martin, B.D. Hilton, K. A. Blinov, and A. J. Williams, J. Heterocyclic Chem., 45, in press (2008).

This is the list I currently have. Note that this list does not contain additional papers that pertain to homonuclear covariance processing methods. I don't have that list of publications handy that I can cut and paste into this post.

Thanks Gary!

Manuals, Technical Notes, Movies, Doh!

What kind of supporting documentation do you prefer to follow when you attempt to learn a new piece of software?

The inspiration for my last post on Ease of Use came from a discussion I had with my colleague Arvin Moser. Arvin has spent many years with ACD/Labs as a Technical Support Specialist for ACD/Labs and is now an Application Scientist. Arvin knows the learning curve of ACD/Labs software very well.

Following my post last week Arvin and I continued an interesting discussion about user manuals and their usefulness. Arvin was kind enough to summarize our conversation for me and here it is:

Ask anyone who buys a piece of software for their computer whether they feel better that software comes with a manual and chances are everyone will say YES. The thought of having a manual is like a security blanket in case things go bad.

http://en.wikipedia.org/wiki/Instruction_manual_%28computer_and_video_games%29

Since there are so many variations of manuals, let me list what I deem to be a manual, or at least what I’ve seen that comes with a piece of software. There are the instruction manuals, the tutorials, the guides, and reference manuals. They can be stored on a DVD, online and/or in hardcopy form. Online manuals are a convenient way for those users who cannot seem to find older or lost manuals. Electronic manuals have the advantage of allowing key word searching and thus narrow done the bit of information you really need.

Taking it a step further, how many people actually spend the time to read the manual? I doubt that number would be very high especially if it spans more than 20 pages. Most people like to install software and run with it. How many people do you know that have read the manuals that come with Microsoft Excel 2000, 2002, 2003 and 2007? Not a very exciting read, I'm sure.

To simplify matters, many pieces of software come with a quick guide sheet that holds the crucial instructions on a single piece of paper. Not bad and probably the easiest thing a computer company can do to help out its users.

How about those people who do not like to read or can’t read? Then what? Movies are a great way to teach visually what sometimes cannot be easily explained with words and diagrams. Interactive movies add the benefit of enabling viewers to test what they learn without messing up the software directly. Other things that come to mind are word of mouth from an expert user (i.e. Live Help http://www.skype.com/intl/en/share/buttons/), technical support, user forums, and on-site or online training sessions. In a society built on diversity, the key seems to be to provide venues to satisfy as many people as possible.

There are so many possibilities. Let me pose this question:

Should a company that produces software offer all these facets?

What facet do you prefer?

Feel free to add your comments on the blog. 

ACD/1D NMR Assistant Part 1-Processing

So here is my first attempt at showing you some of the features available in ACD/1D NMR Assistant.

The first video will highlight how easy it is to process an NMR spectrum in 1D NMR Assistant.

Make sure to check back early next week and I will post another video showing how the software can help you assign your data.

Enjoy!

If you can't get the above video to work, or if you want a bigger version , click here to watch the demonstration.

A note to people who receive this post via email or RSS feed. If you would like to watch the video, you may need to come to the blog to check it out if you can't see it in your reader:

New Product Time! Introducing ACD/1D NMR Assistant

I apologize for not posting much lately, but things have been pretty busy in the ACD/Labs NMR world.

I have alluded to this moment in some previous posts for awhile now and I am now happy to unveil a new NMR product to be offered by ACD/Labs.

ACD/1D NMR Assistant.

So first and foremost, what is it?

I have talked a lot about how synthetic chemists currently use ACD/Labs software and blogged about the benefits and key features in the software.

The bottom line for us, was that while we have been successful in selling
ACD/1D and 2D NMR Processor to chemists and students in industry and academic institutions, we believe that there was still quite a bit of work to be done to design a tool for the chemist.

The truth is, ACD/1D NMR Processor has been around for quite some time. From the very beginning, we were developing a product with the NMR Spectroscopist in mind. Naturally, during the evolution of this product many sophisticated and advanced features have been added and as a result the software can sometimes be viewed as bloated, and overly complex for a novice or non-expert user.

In recent years we have worked hard on continuing to add advanced features but to also try and simplify things. At the end of the day, we made the decision to go in a different direction and create a separate product. This way we can continue to develop ACD/1D NMR Processor with the Spectroscopist in mind, and build ACD/1D NMR Assistant with the synthetic chemist in mind.

So as a result, we developed ACD/1D NMR Assistant and it is now finished and available.

How is ACD/1D NMR Assistant different than ACD/1D NMR Processor?

1. Ease of Use- ACD/1D NMR Assistant includes all of the features available in ACD/1D NMR Processor, we have just de-emphasized some of those features in the software in an effort to greatly simplify the toolbars and interface. I believe that we reduced the learning curve significantly. One example is that upon file import an FID will automatically get FT'ed, phase corrected, and baseline corrected. In addition, the software will look for solvent and water signal automatically and darken them out. Because it includes Shortcut Mode from NMR Processor, users can peak pick, integrate, and characterize multiplets with one simple click and drag over each multiplet.
2. Assignment Assistance- The big improvement added to ACD/1D NMR Assistant is that the software can now provide the user with feedback on potential assignments. When a structure is proposed users can hover over a multiplet of interest and the software will provide real-time feedback as to what the best assignments are. It does so by highlighting atoms in a structure with a green, yellow, and red color scheme.
3. Structure Verification- Whether a user simply wants to check their own assignments, or ask the software to provide feedback on the consistency between a proposed structure and an experimental spectrum, the software provides this capability via one simple button click. If the software deems a spectrum-structure pair as inconsistent, it provides direct feedback on which part (or parts) of the spectra should be looked at closer and what the specific problem is.
   

The ultimate motivation behind this product was the simple idea that, "an NMR spectrum is a means to an end"

While there are several software packages that can process NMR data and print out spectra for evaluation, there is nothing available that really helps users evaluate and interpret an NMR spectrum  and it's relationship with a chemical structure.

That is until now, IMHO.

I think the development of ACD/1D NMR Assistant changes all that.

One more thing...

This product wasn't just built by a few software-oriented people within ACD/Labs. We have been speaking with current customers and chemists for years on how we can improve our offering. I personally have spent a very considerable portion of the last 2 years speaking with chemists, students, and spectroscopists who support chemists, discussing what was lacking in our current offerings and how we can improve our software for these users. Further, I spoke with people who have never used ACD/Labs software and discussed their desires and expectations for an NMR package that would suit their needs.

Finally, after the first stage of new development we sent the software to groups of chemists in 5 different pharmaceutical organizations in the US and had them evaluate the software. These groups ranged from chemists who currently used our 1D NMR Processor, to chemists who had never used it. In doing this we hoped we would be able to appropriately gauge the acceptance and learning curve of the new software. This wasn't beta testing...this was MARKET testing. We are very grateful to these chemists who provided valuable feedback that was implemented in the final version of the software. They were able to point out some very obvious things that our software-focused minds simply overlooked for years.

Following these evaluations, we took the feedback we received and performed another round of development + evaluation to optimize our offering.

And through those exercises, we reach today. A finished product in hand that I am very excited about.

Over the next few weeks, I will be highlighting different features and workflows in the software to educate you on how it works and what it does.

For those of you who want a sneak peek right now, go over to the ACD/Labs website and view the movie that shows the software in action. If you like what you see, just fill out the form at the bottom of the page and you can get a free evaluation copy to try yourself.

Click here to go to the 1D NMR Assistant page.

I hope you like it!

Fringe Benefits and Knowledge Management

Last week I blogged about Phil Keyes' and Anthony Macherone's applications of NMR software towards automated structure confirmation.

A few months back, I pointed you to Steve Coombes' workflow when working with ACD/Structure Elucidator.

Phil had a very nice section in his presentation about the "fringe benefits" he was able to derive outside of the main goal of the project, "Automated Structure Verification".

Specifically, Phil pointed to a couple of fringe benefits:

1) A spectral database is grown as a result of the automated structure confirmation. This database is heavily searchable and can be used as a resource within the company. Building the database is part of the workflow. No extra work needs to be done.

2) The software provides an assignment starting point. In running the verification algorithm, the software automatically attempts to assign multiplets in the 1D and 2D spectra, provides feedback of the quality of those assignments, along with the ability to easily edit them:

Anthony Macherone also mentioned automatically storing data in a searchable database as an additional benefit to conducting automated structure confirmation in his presentation.

On a different application, Steve Coombes spoke a lot about the additional benefits he receives out of ACD/Structure Elucidator.

In this presentation Steve really stresses the knowledge management angle from Structure Elucidator. Sure, the software can help elucidate the chemical structure of unknowns, but it also supports the ability to store the knowledge you gain from working on your data.

In Steve's opinion this is what separates ACD/Labs software from many other packages out there. The "ability to extract the information and knowledge for further use"

It's not just the ability to build databases with structures and spectra. The key is the ability to assign that data electronically and store it in a searchable database. That's knowledge.

And of course by retaining that knowledge through electronic assignments, you can share that knowledge with the software by training the predictions and improving elucidation and verification performance. 

I'd like to thanks these guys for teaching me a nice "marketing" lesson. It's not always about the main application of the software. Always be on the lookout for "fringe benefits"

Meet Quindolinocryptotackiene

Tony over at ChemSpider takes us on a trip down memory lane to one of the most successful stories surrounding Computer Assisted Structure Elucidation (CASE).

It is also the best example of achieving symbiosis between a spectroscopist (in this case Gary Martin) and software (ACD/Structure Elucidator) I have ever seen.

He is referring to "Solving a structure computationally after 10 years of human effort" that was presented by Gary and Tony at the ASP Meeting in 2003 (It's a long presentation but skip to slide 44 to get to the meat of the presentation).

There is also a publication on this story. 

Tony's purpose for resurrecting this story is as follows:

Now, we THINK we have it elucidated correctly. However, we would like to confirm it. Synthesis of the molecule in question, further NMR data generation and a crystal structure would help finish this work fully. This is a call to organic chemists to participate in a hobby project. Anybody want to help? We guarantee a publication etc. The structure is shown below. Contact me at antonyDOTwilliamsATChemspiderDOTcom. Thanks!

Hopefully someone is willing to step up to the plate.

I'd also like to take this opportunity to, once again, point out that CASE is not simply about piling a bunch of data in a piece of software and getting the answer out the other end. Sure this is possible, but it usually benefits when an experienced spectroscopist works with it and shares their knowledge of the existing chemistry. I think Gary's story is a perfect example of that.

That being said, in Gary's case, along with comments I have received from Dr. Shaun Tennant (another elucidator user) in the past, the software is an unbiased approach that will propose some things that the spectroscopist simply might not think about. Knowledge can sometimes be your enemy.