As I mentioned before in this blog, I have spent the last year and a half visiting with medicinal and process chemists, as well as NMR Spectroscopists who support chemists in an open access environment. I‘ve been trying to understand how NMR software is being used in these environments and how things can be improved in this world.
Of course the convenience of having NMR software at their desk or in their lab is a major bonus. J-Coupler and the ability to produce a multiplet report in journal format for patents and publications is always a huge hit.
A few weeks ago, I blogged about how chemists use NMR and I also questioned the information (or lack thereof) in archived data, and spectra in reports.
I am going to riff a bit about what I have learned about compound registration. In the great majority of medchem groups I have spoken with, a compound is synthesized, an NMR and sometimes an LC-MS is run, and then a registration form is filled out. This registration form consists of a check box where the chemist selects which experiments were run and a statement such as, “the structure is consistent with the data collected”
My question is, what happens with this data? Generally this data will be pasted in a chemist’s lab notebook, or maybe even in their ELN if the organization is that far along. But for the most part this is just data. Whether it’s a printout or an electronic file, it’s generally just the data. Maybe there is a structure attached, and some chemists will diligently assign their spectra to their structure on their printout.
But the issue I see here is that there is no consistency. There is no mandate at the top that is telling the chemists to provide support of a proof of structure. A 1H NMR and mass value cannot provide a full proof of structure…but how exactly is a simple statement like, “the structure is consistent with the spectrum” validated? Certainly it’s not validated from a paper printout of a spectrum.
I hope people realize that my intention is not to call out chemists. The chemists are not the problem here. Their job at this particular stage is to make compounds and fill out a registration form (forgive me for being overly simplistic). Their job is not to fully assign their data and prove that at least there is nothing in the data that suggests an inconsistency. Again, a 1H NMR is not going to be a proof of structure. But it was run for a reason, and that reason should be validated.
I’ve talked to many chemists who are very diligent about their handling of NMR data. They will use our software and fully assign their data to a chemical structure and ensure that there is no inconsistency. They do this not because they have to, but for their own piece of mind, and because they believe it is the responsible thing to do. But again, the problem is consistency. For every chemist who is diligent about their NMR data handling, there are several more that don’t do it. In fact, there are perhaps some who run the NMR but don’t look at it. The identity of their compound is confirmed by a mass value, and in the environment they are working that is perfectly acceptable. I personally don’t blame them for not spending the extra couple of minutes to fully assign their data. It’s not their job!
Maybe I am out of place…maybe I am misunderstanding the environment or the reasoning behind not taking this direction. Perhaps this just isn’t the right time to bring this issue up. But in the age of electronic lab notebooks, to me, it seems like a perfect time to discuss and implement this.
But in an industry that is so heavily regulated, it blows my mind that a chemist’s decision to register a compound is based on good faith.
Perhaps an expert in this area can clear things up for me and put me in my place. I am simply trying to espouse the benefits of our software. I believe assigning NMR data electronically to structures has major benefits.
P.S. There’s another benefit. Imagine chemists in an open access environment fully assigning all of their NMR data and then sending it off to an NMR Spectroscopists. This will create a purgatory database for the NMR spectroscopist to evaluate. Once quality checked the spectroscopists can build a database of all this information and in turn, vastly improve the NMR prediction capabilities within the organization.