Ryan's Blog on NMR Software

Hope to See you at SMASH 2009

If you are attending SMASH in Chamonix next month please make sure to drop by and see my colleagues and I. We'll be happy to show you what is new in the software, and what we are thinking about moving forward.

In addition, on Sunday, Sept. 20th at noon, we will be holding our annual symposium where representatives from ACD/Labs as well as some of our guest speakers from industry and academia will share the latest developments and applications of our software.

We will be discussing primarily our work, and the work of others toward Computer Assisted Structure Elucidation (CASE), Advances in Automated Structure Verification, as well as the progress we've made on our new  ACD/NMR Workbook release.

I am delighted to welcome as guest speakers, Anna Codina from Pfizer Sandwich, Duncan Farrant from GSK, Stevenage, and Craig Butts from Bristol University.

To see the full agenda for our symposium, and to register online, please visit:

http://www.acdlabs.com/um/2009/smash/seminar.html

Please register and join us for a free lunch prior to the symposium.

I realize travel budgets are tight these days, but it's a great conference, a great program, great people, and a wonderful location.

I hope to see you there.

How do Medicinal and Synthetic Chemists use NMR Software?- Part 6

This is a continuation of a series of posts that began here.

In the previous post of this series, I discussed how chemists can extract multiplet reports in journal format on the fly using the same procedure to re-cut integrals in the spectrum. Well in addition to having this nice reporting tool, the software can make valuable use out of this multiplicity information.

The software has the ability to assist the chemist with the interpretation of their spectrum. It does this by using the NMR prediction algorithms embedded in the software. With the use of these algorithms structure interpretation and verification can be employed.

Essentially when a chemical structure is attached to a spectrum, the software will predict a spectrum in the background and automatically compare the predicted spectrum to the experimental spectrum. To do this automatic evaluation, the software will compare three properties between the spectra:

1) Chemical Shift
2) Integration
3) Multiplicity information

As a result, by re-cutting your integrals in the software (and hence defining multiplet patterns and coupling constants) the software will use this information to help a chemist interpret their spectrum. Specifically, it will use this information to provide the chemist with immediate feedback as to what atoms in the chemical structure a multiplet is consistent with. See the movie below:

How do Medicinal and Synthetic Chemists use NMR Software?- Part 5

This is a continuation of a series of posts that began here.

In my last post, I promised to address how, by simply spending 2 minutes re-cutting their integrals, a chemist can extract much more valuable information from their spectra.

The #1 thing in our NMR software that blows chemists away is the production of the following:

¹H NMR (DMSO-d6) Shift d: 7.90 - 7.95 (m, 2H), 7.79 (s, 1H), 7.45 (d, J = 8.6 Hz, 1H), 7.33 (dd, J = 8.6, 1.8 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 4.21 (q, J = 7.1 Hz, 2H), 2.53 (s, 1H), 1.25 (t, J = 7.0 Hz, 3H), 1.24 (t, J = 7.1 Hz, 3H)

To elucidate and format this information for experimental sections in patents, reports, and publications, this is a very time consuming process by hand.

Can software make it easier?

This capability has been available in our software for a long time. However, in older versions of our software, while it was much easier than doing it by hand, it was a little time-consuming and not obvious how to do this. For example you would have to first pick your peaks in peak picking mode, then you would have to integrate those peaks in integration mode, and finally you would enter Multiplet Mode and create those multiplets. 

As I've already mentioned, Chemists like to re-cut their integrals to make them look nice and normalized. Well now, when chemists do this procedure they are also peak picking and defining multiplet patterns and extracting coupling constant on the fly. Below is an 11 second video clip showing this capability in action. 

Prior to the implementation of this feature, using our software to create these reports was something that was done around patent-writing time. If a patent was being written and experimental sections were needed, the chemist would go back to find their old spectra, and create these reports then.

Now that this process is so quick, easy, and intuitive, I've talked to many chemists around the world who are creating multiplet reports for virtually every spectrum they acquire. They can then paste their multiplet information in a report or ELN, and it will save them time in the patent writing process down the road. And that's not the only benefit chemists can potentially get from extracting this information each time they acquire a spectrum. I'll talk about another, next time.

I wish all the Moms out there a Happy Mother's Day!

How do Medicinal and Synthetic Chemists use NMR Software?- Part 4

This is a continuation of a series of posts that began here.

Here's a short and sweet one.

In my last post, I talked about how having immediate access to the processed data is something that most chemists like. From there, for a lot of chemists the workflow is very simple. Let's just get the integrals looking nice.  Note: They don't generally look nice from automated processing off the instrument unless multiplets are really well resolved and separated.

So for some chemists, re-cutting their integrals and then printing off the spectrum, just might be the peak of their use of an NMR software package.

But what if this very simple process that generally takes no more than 2 minutes could also provide the chemist with much more valuable information about their spectrum beyond integrals?

I'll address that on my next post. 

How do Medicinal and Synthetic Chemists use NMR Software?- Part 3

This is a continuation of a series of posts that began here.

I learned an interesting lesson a few years ago when I was presenting our software on-site to a group of chemists. I began the demonstration by opening up an FID. The response from most of the room was a mix of confusion as well as horror! What is that squigly line you have up on the screen?

It was then I learned that most chemists don't need fancy processing, nor go through the manual steps of FT, baseline correction, phasing, etc. Provided that the sample was prepared and acquired well, the chemist generally doesn't need to do anything fancy to make their ¹H NMR spectrum look reasonable.

This is why in many open access environments that I have visited, chemists are not required to process their data at all. No need to FT their data, nor baseline correct it, nor phase it.

This can be accomplished in a couple of different ways.

You can supply the chemists with processed data from the instrument. In Bruker-speak that's the 1r file. In Varian-speak, it's a phasefile. This is really useful for a chemist because it saves them the additional mouse-clicks for processing data every single time. The only drawback of this approach is that the integrals are usually not all that nice. So a standard workflow for this, is deleting the integrals and re-cutting them a small price to pay, in my opinion.  And of course there are always going to be some cases where the phasing is off, or the spectrum will need some additional baseline correction.

Some other ways, for example, in our software, is to use macros to automatically process the data with one button click. Essentially, you need only create a macro with all the steps set to your liking. Once complete, you can use this macro on all your data. Simply import the FID and click the button. Of course you can also import processed Bruker or Varian files and work with them straightaway in the software. Finally, one of the things we added in the software back in version 10 was Shortcut Mode. With this mode, when you import or drop an FID into the software, it will auto-execute a set of pre-defined processing steps. For example FT, phasing, baseline correction, weighting functions, etc.

All in all, there are a variety of ways to greatly simplify the software interaction for a chemist. I recommend if you are a chemist, or the NMR person responsible for setting up the instrument, that you investigate the possibility of getting direct access to processed data. From there, it's just a matter of cutting integrals, and you're away!

How do Medicinal and Synthetic Chemists Use NMR Software?- Part 2

This is the continuation of a series of posts that began here.

Have you ever worked in an environment where there was a walk-up NMR lab?

If yes, were you fortunate enough to have software in your office or lab where you could view, process, and print out your own plots at your convenience?

If no, then you can relate to having to walk down to the NMR lab to get your print-out only to realize that all you really need is a zoomed in plot from 6.4 ppm -7.3 ppm. Or the processing done off the instrument didn't do the integrals the way you like them.

But John the Chemist, is ahead of you in the queue at the only workstation that has NMR software that allows you to do this. So you have to wait around until he's done his analysis, and he just happens to be one of those chemists who loves to use all the bells and whistles in the software :) Did I mention it was 6:30 PM on Friday?

Having software on the computer in your office or lab (or on your laptop) can result in a huge productivity boost. You may not think it, but I have had many NMR people in companies tell me that this where they get most of their ROI from a deployment of software.

The simple fact that chemists don't have to walk down to the lab for every spectrum, or wait in line to use the software, can save a lot of time and grief!

 

How do Medicinal and Synthetic Chemists Use NMR Software?- Part 1

This post will mark the beginning of a series of several posts.

Please note that for this particular series I am talking mostly about medicinal or synthetic chemists who acquire their own NMR data in an open access environment.

Many chemists in the industry use our software, and when we were doing market research and testing to try and develop the best tool for chemists, I came away with several generalizations. I will post these over the next couple of weeks.

I am going to start off this series by talking about what chemists generally DON'T use NMR Software for.

While there are some chemists who will apply sophisticated processing, accurately integrate, peak pick and characterize all multiplets, assign multiplets in the software to an electronic structure, work with a series, write macros, etc. my observations are that these are few and far between. Most chemists are not going to play with all of the bells and whistles within an NMR software package.

After all, it's not their job to do all of that in most cases. Their job is to make compounds and make sure they made what they thought they made oftentimes using a variety of techniques, not just NMR.

J-Coupler Redux

One of the really nice things that has been available in our software for many years has been the ability to characterize multiplet patterns and coupling constants and to quickly generate a multiplet report like this one:

1H NMR (400 MHz, DMSO-d6)  ppm 0.96 (t, J=7.30 Hz, 3 H) 1.27 (t, J=7.18 Hz, 6 H) 1.41 - 1.54 (m, 2 H) 1.71 - 1.83 (m, 2 H) 3.20 (q, J=7.05 Hz, 4 H) 3.26 - 3.31 (m, 2 H) 3.73 (q, J=6.29 Hz, 2 H) 4.45 (t, J=6.55 Hz, 2 H) 7.20 (s, 1 H) 7.47 (ddd, J=8.31, 7.05, 1.26 Hz, 1 H) 7.70 (ddd, J=8.37, 6.99, 1.51 Hz, 1 H) 7.81 (dd, J=8.31, 0.76 Hz, 1 H) 8.09 (dd, J=8.31, 1.01 Hz, 1 H) 9.12 (t, J=5.67 Hz, 1 H) 10.63 (br. s., 1 H)

Now while the generation of this report in this format is as simply as one button click, characterizing the multiplets can be more labor intensive.

In our software you can characterize a multiplet in one of two ways, automatically, or manually. In the automatic mode, with one button click, you can generate multiplet patterns and coupling constants for all of the multiplets in your spectrum. In the manual way, you can generate the peak picking, integrals, multiplet pattern, and coupling constants, by simply left-clicking and dragging over a multiplet of interest. I prefer the latter method (although a close second is to generate them all automatically and then simply go back and check each individual multiplet for errors).

During the development process of Version 12 of our software, based on customer feedback primarily, we took a look at our multiplet analysis routine, specifically at how a user must interact with the software in the case that the algorithm incorrectly characterized a multiplet (due to missed peaks, severe overlap, significant roofing or tenting, etc.)

Let’s consider an example.  I have a multiplet that the software has incorrectly characterized as a doublet of triplets. Instead I want to make this two overlapping triplets. How would you do it pre- Version 12?:

Now in Version 12:

My hope is that, the method to create 2 triplets is MUCH clearer in Version 12.
To come to the decision of how the New Multiplet Analysis Tool should look, we polled a group of people from different backgrounds: Current users, non-users, expert users of our software, novices, spectroscopists, chemists, students, etc.

We provided an example like this one with 5 different prototypes of the J-Coupler dialog box to see which one was the most clear. The new one we implemented in version 12 was obviously first place by a landslide compared to the others. The implementation from version 11 finished dead last in usability testing.

Here’s hoping that you agree!

If you are interested in future usability testing with our software, please drop me a line.

How Do you Report a Proof of Structure by NMR?

For several years many customers have shown me different ways in which they like to report the interpretation of an NMR dataset. While there have certainly been a variety of different approaches, the most common way I have across looks similar to this:

You’ll also find a similar reporting style in journal articles such as the Journal of Natural Products.
When I introduced NMR Workbook on this blog a while back, if you watched the movie, you will likely have found that the NMRSync functionality was the really neat piece: to simultaneously peak pick and assign all multiplets and correlations in a sample dataset.  Certainly, many spectroscopists are already commenting that this is a huge time-saver.

However, the purpose of this post is to also highlight that while saving all that time with synchronous peak picking and assignment, you are also, on the fly, creating a table just like the one above,  that is organizing and reporting all of those assignments you are making in your head and applying to spectrum within the software. We call it the Common Assignment Table, or C.A.T.

What we’ve tried to do with NMR Workbook is mimic the NMR Spectroscopists manual workflow with working with a number of different experiments associated with one sample. However, in addition to doing that, we hope to save you time in the reporting and bookkeeping process. The on-the-fly creation of a Common Assignment Table, along with the already available functionality of multiplet reporting in patent and journal formats, correlation arrows and chemical shift values on the structure, I hope that we have made this reporting process much less tedious and just another reason to embrace spectrum analysis and interpretation in an electronic medium.

How do you report your NMR and proof of structure data?

The Little Things Count

As I mentioned in my last post, with the release of Version 12 out of the door, there are many new and exciting things to explore in our latest release outside of the NMR Workbook.

For me, one of the things that I continue to be amazed about are how much the little things matter to end-users. We spend so much effort and hours to add significant and game-changing functionality like NMRSync, but oftentimes, it is the simplest implementations that make a big difference to the customer's workflow.

Here are a few things that we implemented in Version 12 that have our end-users breathing a sigh of relief:

1) Zoom undo button

The addition of one button can make a big difference. Due to popular demand, we added a toolbar button for the zoom undo feature. Very useful, specifically when you are peak picking a 2D NMR spectrum.Clicking it, allows you to backtrack your zooming.

2) J-Coupler Pop up

In previous version, every time you created a multiplet in the software, the J-Coupler dialog box would pop up. This was a bit of an annoyance for some people, because the only time you need to launch this box, is when your multiplet was characterized incorrectly by the software. Now, whenever you create a multiplet, you get an enhanced label over the multiplet outlining the chemical shift, multiplet pattern, coupling constants, and integral:

 

If the characterization of the multiplet is incorrect, the user simply needs to click on the label to launch J-Coupler and edit their multiplet.

3) Easily Increase or Decrease Multiplet Ranges

Sometimes a user would like to increase or decrease a range for a multiplet of interest. This is especially useful in the case of overlapping multiplets where one multiplet was created originally instead of several. In previous version, users could adjust this range, but only by typing the range in J-Coupler.

In Version 12, we've added an easier way to quickly adjust this range by simply left-clicking and dragging the borders of the multiplet range:

 

4) Spectral Preview Pane

It is now possible to get a quick preview of other spectra without having to make them active by simply hovering your cursor over the respective tabs.

4) MAP in Shortcut Mode

Multiplet Assignment Preview (MAP) was a feature we released in version 11 that helps provide the end-user with assignment assistance. In version 11, when a user entered assignment mode, the software would run a calculation in the background comparing the predicted chemical shift, integration, and multiplicity information with the properties from the experimental spectrum in question. With this information, the software can then suggest the best possible assignments for distinct multiplets in an experimental ¹H NMR spectrum. Unfortunately, this feature went largely undiscovered for many users because it was hidden in assignment mode.

In verison 12, this calculation is automatically run when a structure is attached to a spectrum, and the MAP will appear on the structure as soon as multiplets are created in Shortcut Mode:

From here, the user can quickly assign their multiplets with the aid of the Multiplet Assignment Preview.