In this blog post, I’ll explain in simple terms how NMR helps determine the order and manner in which atoms are bonded within a compound.
Why Do We Need to Know the Order of Atomic Bonds?
Just like the childhood joke, “What do you get if you split an ant into three parts?”—which makes us laugh—questions about the components of matter are much more serious and important in chemistry. If asked what atoms result when a water molecule is split into two pieces, most people would answer hydrogen and oxygen. Similarly, carbon dioxide is said to consist of carbon and oxygen. In other words, compounds are composed of atoms as their basic units, and it was relatively easy to determine which elements were present using classical analytical methods such as combustion.
However, simply knowing which elements are present is not enough. This is because even the same atoms can exhibit completely different properties depending on the order or manner of their bonding. For example, acetone and propanol, which have the same molecular formula (C₃H₈O), are used for different purposes. Therefore, in chemistry, it has become important to go beyond simply asking “what is it made of?” to elucidating “how are the atoms connected?”—and methods to clarify this bonding order and structure have become necessary.
Returning to the example of water, it is difficult to determine with the naked eye or through simple manipulation whether water is H-O-H or H-H-O (though, of course, it is actually H-O-H). Techniques for determining the order of bonds and the presence of neighboring atoms are fundamental and essential for understanding the properties and functions of molecules. One of the widely used analytical methods to solve such problems is NMR.
The Principles, Applications, and Limitations of NMR
NMR stands for “nuclear magnetic resonance.” While the name may sound complicated, the concept is simple. When an external magnetic field is applied to the “spin”—an intrinsic property of atomic nuclei—the nuclei align in a specific direction; if energy is then applied, certain nuclei absorb that energy and change their state. The energy absorbed at this point varies slightly depending on the type of nucleus and its environment within the molecule—that is, the presence and position of surrounding atoms. NMR measures these subtle energy differences to determine the arrangement of atoms and identify which atoms are nearby.
To explain this in more detail, atomic nuclei tend to align their spins in the opposite direction of the external magnetic field, and this alignment ultimately generates a magnetic field. The induced magnetic field generated by the nuclei acts in a direction that weakens the external magnetic field; this principle is similar to the tendency of a rubber band to contract when it is stretched. When specific energy levels are applied sequentially to the nuclei in their alignment state induced by the external magnetic field, each atomic nucleus absorbs the energy that corresponds to its own frequency, causing resonance, and structural information about the interior of the molecule is obtained from these results.
Although NMR is classified into various types depending on the target nuclide, the methods most commonly used to elucidate bonding structures are H-NMR (hydrogen nucleus spectroscopy) and 13C-NMR (spectroscopy of the carbon isotope 13C). H-NMR reveals the positions of hydrogen atoms within a molecule and which atoms they are bonded to. 13C-NMR is used to determine the environment of carbon atoms.
This may raise the question: why can’t atoms like oxygen be used in NMR analysis? The reason is that not all atomic nuclei possess the “spin” required for NMR. Nuclides with even atomic numbers and even mass numbers often have a nuclear spin of 0; they lack magnetic properties and therefore do not produce an NMR signal. For example, since common carbon-12 cannot be directly observed, the isotope carbon-13—which exists in minute quantities in nature—is used instead. Conversely, hydrogen has a nuclear spin and is abundantly present, making H-NMR the most widely used technique.
The scope of NMR applications is very broad. Structural information can be obtained via NMR for everything from small organic molecules to polymers and large biomolecules such as proteins. Since the primary elements constituting biomolecules are limited to hydrogen, carbon, oxygen, and nitrogen, determining the bonding relationships between these atoms using NMR is extremely helpful in elucidating the three-dimensional structure and function of proteins.
Furthermore, the principle of NMR is also at the core of MRI (magnetic resonance imaging), a medical imaging technology. MRI, used in hospitals, applies the NMR principle to hydrogen atoms within the human body (primarily hydrogen from water and fat) to visualize tissue structures. Unlike X-rays, it does not use strong radiation, making it harmless to the human body, and since most of the human body contains hydrogen, detailed images can be obtained.
Of course, NMR has its limitations. As mentioned earlier, not all atoms are suitable for NMR observation, and some elements are difficult to observe directly. However, when NMR is used in conjunction with other analytical methods, such as mass spectrometry (MS) and infrared spectroscopy (IR), it can provide complementary information about atoms other than hydrogen and carbon. By combining these techniques, it is extremely rare in modern chemistry to encounter a case where a molecular structure cannot be determined.
In conclusion, NMR is one of the most fundamental and powerful tools for elucidating unknown compounds. From the historic achievement of analyzing the molecules in a cup of water to determine how hydrogen and oxygen are bonded within it, to today’s protein structure determination and medical imaging, NMR has served as a window into the molecular world. As analytical techniques continue to advance, we may eventually require such sophisticated information that answering a simple question like “What happens when you split water?” might necessitate an explanation spanning several pages of A4 paper. Even then, NMR will remain a crucial foundation.
