NIUMAG
Nuclear magnetic resonance (NMR) spectroscopy dominates the discovery of fragment-based lead compounds (1) in a recent survey of pharmaceutical discoveries – scientists looking for the next blockbuster drug to use. In addition, food fraud investigators used NMR technology to identify milk fats and/or milk proteins in products such as imitation cheese and ice cream that were replaced with lower-cost non-milk components such as soy, starch or vegetable oil (2).
Nearly 60 years ago, when Dr. Gunther Laukien (now the father of brook’s CEO) published his seminal paper, high-frequency nuclear spectroscopy, in the 1958 encyclopedia of physics (3), he and other pioneers built their first instruments, modern NMR applications would go far beyond their imagination.
This paper reviews the work of the technology’s creators and reflects on the key advances that have propelled NMR to its current position — as the technology of choice in the search for an information-rich, lossless analytical tool to reveal the structure, characteristics, concentration, and behavior of molecules in solid or liquid samples.
Past
NMR was inseparable from the early development of the two major companies that established the field, Bruker and Varian. Gunther Laukien studied physics at the university of Tubingen and moved to Stuttgart to work at the institute of experimental physics in 1952.Working on NMR technology, he conducted post-doctoral research in NMR spectroscopy and published a pioneering paper on high-frequency NMR in 1958.The paper describes the theoretical aspects known at the time, but also covers practical considerations for constructing experimental systems. In 1960, he was appointed professor of experimental physics at the University of Karlsruhe.
Varian was founded in 1948 by Stanford university scientists in the Stanford industrial park. One of the company’s early goals was to commercialize the NMR spectroscopy technology that Felix Bloch co-discovered in 1946.Edward m. percel and Felix Bloch were later awarded the 1952 Nobel Prize in physics for this work.
While Laukien was researching, Varian began building the first commercial high-resolution spectrometer .Based on continuous wave scanning method and electromagnet, it is designed for analytical chemistry .Laukien recognized the power of the technology and saw a market for pulse spectrometers, but there were no commercially available devices. He set about setting up his own company to meet this need, setting up brook physics in 1960.
The intense competition between the two companies drove the early development and innovation of many NMR technologies.
Present
After nearly 30 years of development, NMR analyzer has become a mature technology and has been widely used. There is hardly a paper in the field of organic chemistry that does not report NMR data.
Next, let us look at the development of these initial systems, and identify three key areas of development that have led to today’s systems: higher magnetic field strength to improve sensitivity; Probe technology improvements and new design to improve performance; And rapid advances in computer power have allowed software to be developed to simplify data processing and open up the technology to non-specialists. The timeline below highlights some of the key milestones in the second wave’s development. Interestingly, a number of NMR pioneers and early adopters have provided personal accounts and reviews of the technology’s development over the decades from 1980 to 2010, providing a wealth of fascinating insights
Future
NMR’s influence continues beyond its traditional applications. For example, the following highlights were included in the presentations and posters presented at the small molecule NMR conference (SMASH) in September 2016:
• practical application of two-dimensional NMR non-uniform sampling (NUS) in the pharmaceutical industry
• use the residual dipole coupling constant to determine the configuration of small molecules
• NMR spectra are used for the identification of monoclonal antibodies
• place NMR on the desktop – low field and desktop NMR
In addition, many papers in the journal have proposed or commented on the potential contributions of NMR in a number of important new areas. Many represent significant changes in the application of NMR spectroscopy: in metabolomics, for example, statistical analysis can reveal markers of a metabolic disorder or disease by collecting large amounts of spectral data and basic data on metabolites. Once a model is established, measurements of a single sample can determine whether the sample is normal or abnormal, and even diagnose the nature of the disease. This requires NMR and sends it to the clinical scientist.
In the field of biopharmaceutical, researchers are using NMR techniques to characterize the structure of monoclonal antibodies (mAbs).Another application of NMR technology in the production or amplification of biological agents is to monitor the composition of growth media. Recognition of the depletion of certain nutrients or the accumulation of potentially toxic metabolites can significantly improve yield and fermentation efficiency.
The use of fluorine in the pharmaceutical industry has increased dramatically in the past few years. Today, five of the top 10 best-selling small-molecule drugs contain fluorine.F19NMR provides a unique method not only for drug discovery but also for characterization and quantification of fluorine-containing molecules. At the same time, some cryogenic probes with high sensitivity were introduced to observe nuclei.
With the latest research in structural biology, natural products, polymer science, petrochemical products and materials science, new applications seem to be emerging.
Conclusion
More than 70 years ago, a brilliant scientist first measured nuclear magnetic spins, work that eventually won him a Nobel Prize in 1943.From the mid-1950s to 2010, a small group of companies inspired each other to develop NMR related technologies, instruments, and applications, and the scientists who used the NMR system in the laboratory were very innovative in the way it was applied. Initially, Bruker and Varian competed fiercely, but brook gradually became the dominant player and continues to do so today, working with customers and partners to build the application base and develop new tools. As can be seen, NMR has become an essential tool for many industries, and its innovations continue as it expands into new methods and applications.