Nuclear Magnetic Resonance Spectroscopy

This article appears in Joseph D. Martin and Cyrus C. M. Mody, eds., Between Making and Knowing: Tools in the History of Materials Research, WSPC Encyclopedia of the Development and History of Materials Science, vol. 1. Singapore: World Scientific, 2020.

The introduction to this section discusses how spraying things at materials can be a method for learning about their properties. Nuclear magnetic resonance (NMR) spectroscopy works in a similar, but subtly different way—it induces the materials themselves to do the spraying. NMR is a phenomenon that occurs when the nuclei of atoms in a strong magnetic field resonate with small oscillations in the near field (the portion of the magnetic field close to them) generated with radiofrequency (RF) pulses (figure 1). The resonance causes nuclei to give off electromagnetic radiation, which carries information about the properties of those nuclei—in particular their magnetic moment, which can identify elements and give hints about how atoms are arrayed in a crystal or molecule. This information can be invaluable for determining molecular and crystal structure, monitoring chemical reactions or biological processes as they unfold, analyzing the purity of samples, and for applications like imaging. NMR has therefore become a widespread technique for investigating physical, chemical, and biological materials.

Swords into Plowshares (into Swords into Plowshares)

Today, we think of NMR spectroscopy as a civilian technology, but it owes much of its early development to wartime, following what Paul Forman calls a “swords into plowshares” trajectory.(4) The phrase refers to a line from the biblical book of Isaiah: “they shall beat their swords into plowshares, and their spears into pruninghooks: nation shall not lift up sword against nation, neither shall they learn war any more.” World War II inspired vast investment in science and technology for military applications, in particular in the United States where NMR techniques were first developed, and from where the early instruments and expertise disseminated. After the war, opportunities emerged to find new applications for much of this expertise. NMR spectroscopy was one of the techniques that owes a considerable debt to the fruitful program of radar research conducted during the war.

But it is also a reminder that the swords-to-plowshares transition is not a one-way street; plowshares can equally well be beaten into swords. Isidor Isaac Rabi’s research on magnetic resonance in molecular beams at Columbia University, which laid the groundwork for NMR techniques and for which he won the 1944 Nobel Prize, dates to 1937.(10) Rabi’s work in the 1930s was fairly abstract. He was interested in measuring the quantum spin of atomic nuclei. Because the spin of an atomic nucleus is related to its magnetic moment, this work was of relevance to fundamental questions about both nuclear physics and magnetism.

In addressing these questions, Rabi and his team also developed what proved to be a fundamental technique. They began with what was known as a Stern–Gerlach experiment, in which a beam of atoms (usually silver atoms) is passed through an inhomogeneous magnetic field. The splitting of the beam demonstrates that the quantum spin of the atoms can take only one of two orientations. The insight that turned this rather crude apparatus into a delicate tool for measuring nuclear magnetic moment was that, by introducing small, carefully calibrated fluctuations to the magnetic field with RF pulses, it was possible to locate a nucleus’s resonance frequency, where it would absorb RF energy.(14)

It was this fundamental mechanism—the sensitivity of nuclear magnetic moment to small magnetic-field fluctuations—that would lead directly to NMR techniques. But such experiments were delicate and called for the cultivation of considerable instrumental expertise. Interpreting the results of such an experiment required precise knowledge of both the magnetic field strength and the magnitude fluctuations, which in turn demanded exacting calibration. Wartime radar work, which inspired close attention to the way that radio waves interact with both matter and magnetic fields, promoted just that sort of expertise. So, in fact, NMR was not a direct result of military radar research, but rather is “generally indebted to the advance of radio-frequency instrumentation and methods over the course of the war—and to theoretical as well as experimental physicists familiarity with them.”(4 p430) The Radiation Laboratory, or Rad Lab, at MIT incubated considerable advances in the generation, detection, and interpretation of various types of electromagnetic radiation, and so although radar research was not directly concerned with the magnetic moments of nuclei, the instrumental expertise it encouraged created the conditions friendly to the emergence of NMR techniques.

A similar process unfolded on the opposite coast. Before the war, Stanford University was at the forefront of developing the type of equipment that would prove essential for radar technology. Felix Bloch, who would share the 1952 Nobel Prize with the Rad Lab’s Edward Mills Purcell for their independent development of NMR spectroscopy techniques, recalled “acquaintance with radio techniques during the war suggested to me still another and much simpler way,” to detect changes in the orientation of nuclear magnetic moments.(3 p427) But the physicists who developed it, although benefitting from the equipment, concentration of expertise, and instrumentation the war provided, pursued NMR as a matter of fundamental interest—in particular the extension of quantum mechanics to provide a description of the atomic nucleus.(13) By 1960, Bloch would report that “nuclear magnetic resonance has become one of the standard tools of investigation and has furnished one of the most striking examples of the close link between basic research and peaceful applications during the post-war period.”(2)

From Physics to Chemistry and Biology

NMR began as a firmly physical undertaking. Both the instrumentation of radar research and the study of the nucleus were territory claimed by physicists. The birth of NMR also coincided with the postwar emergence of solid state physics as a new and lively subfield.(7) The earliest NMR investigations undertaken by Purcell’s group at Harvard University were simple—identifying the presence of hydrogen nuclei in a sample of paraffin by showing an absorption spike at the predicted resonance frequency for hydrogen’s magnetic moment. But the technique soon demonstrated its superiority over existing tools for particular crystal-structure determinations—the characteristic resonance spikes for certain nuclei would change depending on their structural environment, permitting inferences about that environment. Such structural determinations became more and more germane in the wake of the invention of the transistor at Bell Laboratories in 1947, after which semiconductor physics took off as an area of research. Shortly thereafter, NMR proved its mettle as a tool for assessing superconducting materials as well.(16) From the first, therefore, NMR was a physical tool for physical investigations.(9)

But such an interpretation is necessarily incomplete. As many contributions to this volume demonstrate, instruments have a way of behaving obstreperously with respect to disciplinary boundaries. NMR also had some of its earliest and most notable successes as a chemical technique. Cambridge, Massachusetts, where Purcell brought Rabi’s ideas to fruition, had been a center of molecular theory and an incubator of chemical physics since before the war. NMR was therefore born into an environment with a well-developed community and culture organized to investigate molecular structure. It functioned not as a replacement for, but as a complement to existing techniques like X-ray diffraction and IR spectroscopy, and entered an instrumental community built around those techniques.(11,8)

If NMR offered a new way to apprehend crystal structure, it was a similarly fruitful approach to chemical structure, an area pioneered by the physical chemist Herbert S. Gutowsky.(12) NMR proved particularly useful in this arena once chemists realized that, not only could NMR provide a wealth of data about the overall structure of a molecule, but certain chemical substructures exhibited characteristic NMR signatures, meaning that NMR data was an invaluable supplement to X-ray or IR spectroscopic data.(16) Using these techniques in conjunction vastly expediated the sometimes finnicky task of puzzling out a chemical’s three-dimensional structure.

The wealth of molecular NMR data that accumulated through the 1950s and 1960s paved the way for the application of the technique to more complex molecules—in particular to organic molecules. NMR potential to illuminate protein structure, function, and dynamics was long known. The rise of molecular biology through the 1970s focused attention on proteins, and how both their structure and the ways they assume that structure is related to their function, and NMR’s in-principle ability to trace such processes in real time made it well adapted for such investigations. But the technique did not develop sufficiently to realize that potential until the 1980s, when new techniques like pulse Fourier transform technology made it possible to interpret the often-messy results of such experiments.(17) Here as well, NMR was used in conjunction with other techniques, in particular X-ray crystallography, to create a synthetic picture that no one instrument could provide on its own.(12)

Commercializing NMR

Like many other instruments and techniques discussed in this volume, NMR hatched with the help of government investment in science, fledged in a nest of university research, and then found a new home within commercial enterprises. In contrast to instruments optimized for making materials, however, NMR had a somewhat slower route to commercialization. In its early days, it was an expensive, finnicky, boutique technique, and although the information it provided was scientifically valuable, it was often not directly germane to commercial applications. One reason the NMR community became such a strong, coherent group of researchers, therefore, is because NMR research for some time required a strong command of instrument design and operation of the type that was rapidly becoming less relevant for the operation of black-boxed instruments.

The first company to develop a commercial NMR spectrometer was Varian Associates, which had been founded near Stanford in 1948, in what would shortly become Silicon Valley, to commercialize the klystron. As one of the leaders in tube manufacture, Varian was well positioned and made a few early instruments that made use of the NMR principle. The company actively promoted the new technique with the aim of expanding its market. It organized a series of annual workshops, the first held in October 1957, with the goal of galvanizing the community of NMR researchers and spreading familiarity and facility with the technique.(6,5 p188) When its practical off-the-shelf spectrometer, the A-60, became available in 1962, demand was high and it sold over 1,000 units internationally, most of them to chemical laboratories, before being superseded by newer models in the late 1960s and early 1970s.(1)

The black-boxed machine changed the nature of NMR analysis specifically. Tasks that once took hours or even days could now be completed in minutes. Rather than spending time tinkering with shop-built machinery and fussing over samples, chemists could focus more squarely on the data that machinery generated. Instrument operation, once the province of research chemists, was transferred to technicians. NMR was therefore representative of a broader change in chemical and materials science practice that occurred in the 1960s and 1970s, when the guts of common tools retreated behind the smooth sheet-metal and gleaming dials of prefabricated instruments.(15)

Conclusions

NMR spectroscopy is indicative of a number of themes that are relevant for understanding late twentieth-century materials science more generally. NMR techniques came within reach in the context of the military potential radar offered during World War II and it matured against a Cold War context in which knowledge of materials and recognized as a strategic bottleneck. It crossed disciplines freely, finding a ready welcome wherever the data it provided could prove useful, even if its roots rested firmly in the world of physics. It responded to the subtle give-and-take between instrumental communities and the commercial firms that both served their needs and sought to package the fruits of their labors for new audiences. And the instrument itself became increasingly standardized, its use increasingly routinized—in short, it became increasingly black-boxed as the twentieth century wore on.

We can also see through the story of NMR how interdependent tools for materials research became. The goals of NMR, and the most favorable trajectories for its development, were defined not just by the nature of the phenomena under investigation, but also by the advantages and limitations of existing techniques. Its value was not measured by the information it could extract from samples alone; it was measured too by how that information compared to that generated by X-ray spectroscopy and other techniques. This simple example illustrates the rich, complex instrumental ecology that emerged in the second half of the twentieth century, in which any new instrument, to succeed, had to find its niche.

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