Ryan's Blog on NMR Software

Let's See your Printed Spectra Do This!- Part 2.

Back to the chemists with their ELN who continue to resort to their paper spectra.

Is it just an old habit?

No. I think it is something else. In fact I think there are two major (and completely understandable) reasons why some chemist continue to resist the complete transition to the electronic world:

1. One of our users who I really enjoy speaking with when I get a chance once told me, "The only way you are going to get chemist to fully adopt these tools is when they can access and interact with the spectra JUST as fast as they can do it on paper." I think it's a great point. For some chemists having to sit in front of a new piece (or old piece) of software to try and get your data out can be a daunting task. But I think significant strides have been made in this regard. With the transition to open access, NMR Spectroscopists have done a nice job (in conjunction with software vendors) to automate processing and create software macros to provide chemists with access to fully processed spectra. In addition, I think that the usability of NMR software for manual processing (See Shortcut Mode for example) has greatly improved over the years, but there is of course still work to do.
2. I think the other reason is that perhaps the benefits associated with electronic handling of NMR data have historically been not convincing enough or educated clearly enough to the user. For example, I have beaten the multiplet report topic to death on here, but I am continually amazed by the number of chemists who have had our software for a long time that aren't aware of this feature.

But perhaps easy access to data from your desk and formatted multiplet reports is not enough for a chemist to let go of the paper and embrace the electronic world. In fact, I am convinced it isn't. After all, an NMR spectrum is a means to an end. Sure, the delivery of the results in a readable form in a convenient place is essential and it has increased producitivity in open access environments, but the bottom line is that there is a reason the chemist ran an NMR experiment. In most cases that reason is to determine if their compound's proposed structure is consistent with their spectrum. Historically, NMR processing software has not provided any assistance in regards to data interpretation. 

I am hoping that ACD/1D NMR Assistant addresses this challenge and finally convinces the chemist to let go of their paper spectra for good and fully embrace the electronic world. To see how 1D NMR Assistant helps chemists interpret and assign their ¹H NMR spectra check out my previous vlog postings (with video) here and here.

Are You Attached to the Paper Printouts of Your Spectra?-Part 1

This is the topic I will be presenting on at our annual ENC Symposium on March 9, 2008. If you happen to be attending this conference in Asilomar, check out the agenda and register here.

I mentioned this before, but I follow the Depth-First Blog authored by Rich Apodaca rather closely and I highly recommend it.

I mention it again because Rich had a very interesting post a few weeks back inspired by a discussion about Electronic Lab Notebooks (ELNs) that took place on Derek Lowe's In the Pipeline Blog (which is another blog I follow frequently and highly recommend!)

Fascinating posts and discussion for sure!

Rich notes:

The wasteful process of entombing valuable scientific data often begins with the paper lab notebook, so the subject of ELNs should be of great interest to anyone involved in creating, using, or reprocessing chemical information.

Why do paper notebooks continue to persist in chemistry?

The issue is complex, but in my view stems from the lack of a truly usable and affordable tool. Although the term "tool" may suggest software, it actually involves a much more complex beast consisting of hardware, software, an ergonomic hardware/software user interface, and a computer network. In chemistry, the problem is compounded by the centrality of chemical structures and the inability of most generic ELN products to capture or use them. Given these constraints, and the costs associated with creating and marketing general-purpose products designed to work within them, it's not surprising that many organizations decide to roll their own ELN. And it's even less surprising that many others decide sticking with paper is a better option - at least for now.

I think this is a good argument, and I want to add to it with the question, "Why does paper spectra continue to persist in chemistry?"

Personally, I am amazed by the number of times I have encountered groups who are already using ELNs, but are still routinely using paper spectra. Sure when the time comes to attach their PDFs (Rich has shared his feelings on this format as well, but that's an entirely different discussion!) to their notebook records, they will extract the electronic file, but until that point many chemists will walk back to the instrument room, pick up their data printout, study it, and then toss it in the recycling bin or toss it on their bench!

For example, I was recently visiting with some chemists in the pharmaceutical industry who were providing me with feedback on our products and discussing their workflow. They mentioned that while they religiously use the desktop NMR processing software for viewing, processing, analysis, interpretation, and reporting to their ELN right on their laptops, in their lab...many chemists from their group still make the walk to the instrument room for their piece of paper instead.

Paperless environment?

Old habits, I guess.

Why use a piece of paper when you can access the data electronically? Meaning you can zoom in and zoom out on regions of the spectra to take a closer look? I guess in most cases, you don't really need to do that but in many labs where the data can be accessed electronically on a laptop in your lab, why make the walk back to the instrument room for that piece of paper?

What are your thoughts? Are you still attached to the paper printout? If so, why?

I'll share my opinion in part 2 of this topic tomorrow.

New Blog by Arvin Moser

Those of you who are current users may recognize the name Arvin Moser as he has spent many years as both a Technical Support Specialist and Application Scientist at ACD/Labs.

Arvin has decided to start a blog and share his knowledge and experience about structure elucidation. I think this blog promises to be a very interesting one as Arvin has a wealth of experience in both manual and computer assisted structure elucidation (CASE).

From Arvin's About Page:

My goal is to focus on the science of data interpretation and structure elucidation. I would like to pass on my experiences including what I have learnt from the experts. By sharing these experiences with the scientific community, I think an emerging elucidator can be better equipped with handling anything that comes their way.

Visit Arvin's Blog here.

Dereplication? Version 11- Searching PubChem using ACD/Structure Elucidator

This resource will likely only be useful to readers who are currently using ACD/Structure Elucidator, however, I do have two questions for my general audience and I would greatly appreciate your comments.

First things first, a technical note has been created to explain how to install and search the PubChem Database. It can be downloaded here:

http://www.acdlabs.com/download/technotes/110/nmr/pubchem.pdf

You'll notice in the introductory paragraph of this technical note it uses the term "dereplication" to describe the process of searching a spectral database with the NMR data of an "unknown" prior to elucidation.

Can this process REALLY be called Dereplication?

How do you define the term, "dereplication"?

The first hit from Google (not necessarily the most accurate) provides the following definition:

De`rep`li`ca´tion

the process of testing samples of mixtures which are active in a screening process, so as to recognize and eliminate from consideration those active substances already studied; - a stage subsequent to the preliminary screening in the process of discovery of new pharmacologically active substances in mixtures of natural products; - also called countersceening.

I think this is a reasonable definition based on my understanding of the process.

A few years back, I did quite a bit of research talking to some natural products scientists to try and uncover this idea. I got various different views on the topic and the definition of this term and it's applications. A common response that I got was something like:

"If it is an unknown compound, and I am able to use spectral databases to identify known compounds prior to elucidation, I'd call that dereplication"

And there were this valued added comment:

"If I am able to identify known compounds using a NMR search method, and avoid even two repeat elucidations per year, that's incredibly valuable"

Probably the best, and most comprehensive responses I got were:

"Usually dereplication is done as early as possible in the process. If you have already isolated the compound to NMR purity most of the costs have already been incurred. Typically LC-MS and/or LC-UV on an early crude subsample is the most cost effective. However some pharma use LC-NMR, and using this technique is where NMR database searching can reap rewards."

"Dereplication is done on only a small crude sub-sample of the organism/extract long before large-scale isolation by chromatography is performed. Dereplication only makes sense at an early enough stage in natural product discovery to prevent the high cost isolation chemistry from being undertaken. Hence, only early stage dereplication makes business sense. It would be better to classify dereplication based on the hyphenated techniques. Your late-stage dereplication is really known structure matching/identification - a worthwhile and necessarry pursuit as dereplication is NEVER perfect."

"Searching databases by NMR prior to an elucidation represents dereplication in only some laboratory instances. This workflow would work very well in those laboratories that employ employ LC-NMR as a tool for the separation of natural product extracts. A fraction's NMR spectrum can automatically be searched in a database to identify isolates that contain known compounds. However, this type of analysis is not done in all research labs. Therefore, without this type of analysis, the major costs of natural products research are generally incurred prior to NMR analysis. NMR is introduced as an elucidation tool after separation and purification. A combination of LC-MS and LC-UV, for example, can be used effectively for dereplication purposes as MS can provide an accurate mass and structural information and UV can provide insight on existing chromophores and a compound's structure."

It appears that hyphenated techniques are likely the key to dereplication.

Some good work has be done here using LC-UV-MS, for example:

Merck in NJ:

http://www.massspec.com/downloads/ASMS2006_Poster_Zink_TuP313.pdf

http://www.cosmoscience.org/pdfs/Session%20IV_Presentation%20I_Zink.pdf

Microbial Screening Technologies developed an in-house, metabolite recognition software called COMET that compiles and analyses co-metabolite patterns in natural product mixtures:

http://www.microbialscreening.com/

Dereplication using LC-NMR:

http://www3.interscience.wiley.com/cgi-bin/abstract/76509553/ABSTRACT
http://www3.interscience.wiley.com/cgi-bin/abstract/110574737/ABSTRACT

The late, great John Faulkner once said in a Philosophical Basis for Structure Elucidation:

"The problem with using NMR for dereplication is that no reliable method of searching NMR spectral libraries  has yet been devised, although there have some attempts to construct and search ¹³C NMR libraries. It is possible that computers will, in the future will be able to recognize and compare the patterns that are found in NMR spectra but that seems a long way off."

I think that computers can do this now. But what to call it?

Can an NMR DB search be termed dereplication?

Should it be positioned around and to only those people who use LC-NMR?

What do we call the discovery of known compounds by NMR prior to structure elucidation?

Provide your own thoughts on this.