Magritek is really excited to be at 20th European Symposium on Organic Chemistry 2017 in Cologne, Germany from 2nd – 6th July 2017. You can find us at Booth 12 and we really look forward to meeting you. Our applications and support team will have a live, working Spinsolve Benchtop NMR and will also be there to answer all your benchtop NMR spectroscopy questions.
Dr Jeroen Geuens is a member of the Centre of Expertise on Sustainable Chemistry (CESC) based in Antwerp at the Karel de Grote University College. The Centre specialises in research and services related to chemical and production processes together with offering professional degree courses.
Before discovering the Spinsolve benchtop NMR from Magritek they could only get access to NMR measurements by taking their samples to the University of Antwerp. The Spinsolve is now used continuously for both teaching and research in the CESC. Dr Geuens takes up the story.
Despite the proliferation of new 2D techniques over the past four decades, one of the most commonly used experiments is the very first one to have come into existence, COSY1. It’s easy to see why it’s withstood the test of time: firstly, it’s an extremely useful experiment, providing a direct and easy way of establishing “through bond” proton-proton connectivities (“this hydrogen is near or next to that hydrogen”); secondly, because it’s a homonuclear 2D experiment (that is to say, it correlates protons with protons) its’s a very sensitive one. The high sensitivity also means that it’s a quick experiment to run, particularly if the experiment uses gradients for coherence selection (more on that below and in a future blog post).
Example COSY spectra recorded on Spinsolve can be found elsewhere on the Magritek website, but a typical example is also shown in Figure 1 below, recorded on a sample of ethyl crotonate. The sequence used to collect this spectrum utilizes gradients, meaning that it was run using only a single scan per t1 increment, and with 512 increments it only took 15 minutes to run.
Fig. 1. COSY spectrum of ethyl crotonate, collected using gradients and 512 t1 increments.
In part 5 we introduced the PGSE experiment to measure self-diffusion coefficients. We saw that if the peak integrals are displayed as a Stejskal-Tanner plot we can immediately identify if there is a single self-diffusion coefficient or not. This works pretty well for neat liquids, or solutions with a single type of molecule, or even polymer molecules with a size distribution. However, in real life we are often dealing with mixtures of molecules, and it would be nice if we could somehow separate the spectra of the individual compounds.
Consider for example the spectrum of a mixture of procaine and paracetamol in D2O. This is shown in the middle scan of Figure 1, along with the spectra of the pure compounds above and below. If we had only the mixture available, but not the pure compounds, it would be hard to figure out how many and which compounds are present in the mixture.
These spectra, along with all the others shown in this post, were acquired on a Spinsolve benchtop NMR spectrometer with additional hardware to enable PFGs for measuring diffusion.
Figure 1: Spectra of procaine (top), paracetamol (bottom), and a 1:1 mixture of both (middle) in D2O.
Magritek is really excited to be at the 50th Jahrestreffen Deutscher Katalytiker in Weimar-Germany, from 15th – 17th March 2017. You can find us at Booth 24 and we really look forward to meeting you. Our applications and support team will have a live, working Spinsolve Benchtop NMR and will also be there to answer all your benchtop NMR spectroscopy questions.
In an earlier post on qNMR we described how benchtop NMR can be used to quantify the concentration of a sample or measure its purity. When such quantitative methods are validated, there are standard requirements for accuracy, precision, range, and linearity over that range that need to be met.
For example, the United States Pharmacopeia (USP) specifies the general requirements for a Category I NMR method when measuring a drug substance (there are other specifications for finished products and impurities). These specifications are listed in the table at the end of this post and are compared to the measured Spinsolve performance.
We have validated the Spinsolve benchtop qNMR performance by measuring the purity of one reference standard, methylsulfonylmethane (MSM), with another, maleic acid. Maleic acid is a common reference standard for qNMR, so this was used as the reference to measure the known purity of MSM (specified 99.5% pure). A spectrum of the mixture in D2O is shown in Figure 1.
HTBLA Wels is a higher technical vocational college of chemistry in Austria. Here, Dr Harald Baumgartner is responsible for the instrumental analytical laboratory. The lab’s main focus is to teach students the basics of NMR (interpretation of spectra).
Dr Baumgartner says “Compared to the old 60 MHz spectrometer, the Magritek Spinsolve benchtop spectrometer is so much easier to use. It is software-based so collecting and processing data is quite straightforward. As well as 1H spectra, our Spinsolve allows us to measure more complex spectra including 13C-spectra. Even 2-dimensional experiments are now available to the students.”
A college student learns about NMR with the Magritek Spinsolve Carbon at HTLBA Wels in Austria
Dr Leena Kaisalo heads up the Organic Chemistry student laboratory at the University of Helsinki. While the Laboratory’s research focuses on organic synthesis, Dr Kaisalo’s role is to lead the teaching of bachelor and masters students in various analytical techniques including NMR.
Dr Leena Kaisalo uses her Magritek Spinsolve Benchtop NMR Spectrometer at the University of Helsinki Chemistry Department
Quantification using any analytical method requires calibrating an instrumental response with a known reference, and then calculating the concentration of an unknown sample from the measured instrument response. One advantage of NMR compared to other analytical methods is that the signal response is linear, resulting the NMR signal intensity being proportional to the number of nuclei.
Sample concentrations and purities can be easily measured from known peaks once the proportionality constant is calibrated using a reference of known concentration and purity. Such measurement methods are known as quantitative NMR, or qNMR for short.
Dr Jonathan Harburn is a Lecturer in Medicinal Chemistry in the Wolfson Research Institute located in the School of Medicine, Pharmacy and Health at Durham University. Working together with Drs Stuart Cockerill and Jonathan Sellars, Dr Harburn’s research goals are to create clinical drug candidates for the treatment of viruses, bacteria and cancer.
In their research, recent progress has focussed repurposing novel fluorinated drug fragments on known drug scaffolds to develop hit identification. 19F NMR using Spinsolve is one of the most useful tools in confirming fluorinated fragment incorporation with spectra run in 3 minutes. Also, 1H NMR is routinely carried out for identification before further spectral data is acquired on higher field NMR.
Alistair Paterson, a Level 2 MPharm student at Durham University, uses Spinsolve to evaluate his sulfathiazole sample