Nuclear magnetic resonance

Nuclear magnetic resonance (NMR) is a physical phenomenon based upon the magnetic property of an atom's nucleus. NMR studies a magnetic nucleus, like that of a hydrogen atom, by aligning it with an external magnetic field and perturbing this alignment using an electromagnetic field. The response to the field (the perturbing), is what is exploited in NMR spectroscopy and magnetic resonance imaging.

History

NMR was first described independently by Felix Bloch and Edward Mills Purcell in 1946, (both of whom shared the Nobel Prize in physics in 1952 for their discovery). Purcell had worked on the development and application of RADAR during World War II at MIT's Radiation Lab. His work during that project on the production and detection of radiofrequency energy, and on the absorption of such energy by matter, preceded his discovery of NMR and probably contributed to his understanding of it and related phenomena.

Related Topics:
Felix Bloch - Edward Mills Purcell - 1946 - Nobel Prize in physics - 1952 - RADAR - World War II - MIT - Radiation Lab

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It was noticed that magnetic nuclei, like 1H and 31P, could absorb RF energy when placed in a magnetic field of a specific strength. When this absorption occurs, the nucleus is described as on resonance. Interestingly for analytical scientists, different atoms within a molecule resonate at different frequencies at a given field strength. The observation of the resonance frequencies of a molecule allows a user to discover structural information about the molecule.

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The development of NMR as a technique of analytical chemistry and biochemistry parallels the development of electromagnetic technology and its introduction into civilian use.

Related Topics:
Analytical chemistry - Biochemistry

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Throughout its first few decades, NMR practice utilized a technique known as continuous-wave (CW) spectroscopy, in which either the magnetic field was kept constant and the oscillating field was swept in frequency to chart the on-resonance portions of the spectrum, or more frequently, the oscillating field was held at a fixed frequency, and the magnetic field was swept through the transitions.

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The CW technique is limited in that it probes each frequency individually, in succession, which has unfortunate consequences due to the insensitivity of NMR--that is to say, NMR suffers from poor signal-to-noise ratio. Fortunately for NMR in general, signal-to-noise ratio (S/N) can be improved by signal averaging. Signal averaging increases S/N by the square-root of the number of signals taken.

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The technique known as Fourier transform NMR spectroscopy (FT-NMR) can speed the time it takes to acquire a scan by allowing a range of frequencies to be probed at once. This technique has been made more practical with the development of computers capable of performing the computationally-intensive mathematical transformation of the data from the time domain to the frequency domain, to produce a spectrum as well at the knowledge of how to create an array of frequencies at once.

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Pioneered by Richard R. Ernst, FT-NMR works by irradiating the sample (still held in a static, external magnetic field) with a short square pulse of radiofrequency energy (RF) containing all the frequencies in the range of interest because the fourier decomposition of a square wave contains contributions from all frequencies. The polarized magnets of the nuclei then begin to spin together, creating a RF that is observable. However, they ultimately decay to their ground state (in the magnet) of having a net polarization vector that aligns with the field. This decay is known as the free induction decay (FID). This time-dependent pattern can be converted into a frequency-dependent pattern of nuclear resonances using a mathematical function known as a Fourier transformation, revealing the NMR spectrum.

Related Topics:
Richard R. Ernst - Free induction decay - Fourier transformation - Spectrum

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(A similar technique used for optical rather than NMR spectroscopy is simply called Fourier transform spectroscopy)

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The use of pulses of different shapes, frequencies, and durations, in specifically-designed patterns or pulse sequences allows the spectroscopist to extract many different types of information about the molecule.

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Multi-dimensional nuclear magnetic resonance spectroscopy is a kind of FT-NMR in which there are at least two pulses, and as the experiment is repeated, the pulse sequence is varied. In multidimensional nuclear magnetic resonance, there will be a sequence of pulses, and at least one variable time period (in 3D, two time sequences will be varied. In 4D, three will be varied).

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There are many such experiments. In one, these time intervals allow for, among other things, magnetization transfer between nuclei and therefore the detection of the kinds of nuclear-nuclear interactions that allowed for the magnetization transfer. The kinds of interactions that can be detected are classed into two kinds, usually. There are through-bond interactions and through-space interactions, the latter usually being a consequence of the nuclear Overhauser effect. Experiments of the nuclear Overhauser variety may establish distances between atoms.

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Richard Ernst, Kurt Wüthrich, Ad Bax and many others, developed 2D and multidimensional FT-NMR into a powerful technique for studying biochemistry, in particular for the determination of the structure of biopolymers such as proteins or even small nucleic acids. Wüthrich shared the 2002 Nobel Prize in Chemistry for this

Related Topics:
Richard Ernst - Kurt Wüthrich - Ad Bax - Biochemistry - Biopolymer - Protein - Nucleic acid - Nobel Prize in Chemistry

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work. This technique complements biopolymer X-ray crystallography in that it is frequently applicable to biomolecules in a liquid or liquid crystal phase, whereas crystallography (as the name implies) is performed on molecules in a solid phase. Though NMR is used to study solids, extensive atomic-level biomolecular structural detail is especially challenging to obtain in the solid state. Raymond Andrew was a pioneer in the development of high-resolution solid-state NMR. He introduced the Magic Angle Sample Spinning (MAS) Technique and allowed for an increase in resolution by several orders of magnitude. Alex Pines together with John Waugh revolutionized the area with the introduction of the cross-polarization technique in order to enhance low abundance and sensitivity nuclei.

Related Topics:
X-ray crystallography - Biomolecule - Liquid - Liquid crystal - Solid - Solid-state NMR - Alex Pines - John Waugh

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Because the intensity of NMR signals, and hence the sensitivity of the technique, depend on the strength of the magnetic field, the technique has also advanced over the decades with the development of more powerful magnets. Advances made in the audio-visual technology sector have also improved the signal generation and processing capabilities of newer machines.

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The sensitivity of NMR signals is also dependent, as noted above, on the presence of a magnetically-susceptible nuclide, and therefore either on the natural abundance of such nuclides, or on the ability of the experimentalist to artificially enrich the molecules under study with such nuclides. The most abundant naturally occurring isotopes of hydrogen and phosphorus, for instance, are both magnetically susceptible and readily useful for NMR spectroscopy. In contrast, carbon and nitrogen have useful isotopes, but which occur only in very low natural abundance.

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