Nuclear magnetic resonance

Nuclear magnetic resonance

Nuclear magnetic resonance (NMR) is a physical phenomenon in
which nuclei in a magnetic field absorb and re-emit electromagnetic
radiation. This energy is at a specific resonance frequency which
depends on the strength of the magnetic field and the magnetic
properties of the isotope of the atoms; in practical applications, the
frequency is similar to VHF and UHF television broadcasts
(601000MHz). NMR allows the observation of specific quantum
mechanical magnetic properties of the atomic nucleus. Many scientific
techniques exploit NMR phenomena to study molecular physics,
crystals, and non-crystalline materials through NMR spectroscopy.
NMR is also routinely used in advanced medical imaging techniques,
such as in magnetic resonance imaging (MRI).
All isotopes that contain an odd number of protons and/or of neutrons
(see Isotope) have an intrinsic magnetic moment and angular
momentum, in other words a nonzero spin, while all nuclides with even
Bruker 700 MHz. Nuclear Magnetic Resonance
numbers of both have a total spin of zero. The most commonly studied
(NMR) spectrometer
nuclei are 1H and 13C, although nuclei from isotopes of many other
elements (e.g. 2H, 6Li, 10B, 11B, 14N, 15N, 17O, 19F, 23Na, 29Si, 31P, 35Cl, 113Cd, 129Xe, 195Pt) have been studied
by high-field NMR spectroscopy as well.
A key feature of NMR is that the resonance frequency of a particular substance is directly proportional to the
strength of the applied magnetic field. It is this feature that is exploited in imaging techniques; if a sample is placed
in a non-uniform magnetic field then the resonance frequencies of the sample's nuclei depend on where in the field
they are located. Since the resolution of the imaging technique depends on the magnitude of magnetic field gradient,
many efforts are made to develop increased field strength, often using superconductors. The effectiveness of NMR
can also be improved using hyperpolarization, and/or using two-dimensional, three-dimensional and
higher-dimensional multi-frequency techniques.
The principle of NMR usually involves two sequential steps:
The alignment (polarization) of the magnetic nuclear spins in an applied, constant magnetic field H0.
The perturbation of this alignment of the nuclear spins by employing an electro-magnetic, usually radio frequency
(RF) pulse. The required perturbing frequency is dependent upon the static magnetic field (H0) and the nuclei of
observation.
The two fields are usually chosen to be perpendicular to each other as this maximizes the NMR signal strength. The
resulting response by the total magnetization (M) of the nuclear spins is the phenomenon that is exploited in NMR
spectroscopy and magnetic resonance imaging. Both use intense applied magnetic fields (H0) in order to achieve
dispersion and very high stability to deliver spectral resolution, the details of which are described by chemical shifts,
the Zeeman effect, and Knight shifts (in metals).
NMR phenomena are also utilized in low-field NMR, NMR spectroscopy and MRI in the Earth's magnetic field
(referred to as Earth's field NMR), and in several types of magnetometers.

Nuclear magnetic resonance

History
Nuclear magnetic resonance was first described and measured in molecular beams by Isidor Rabi in 1938, by
extending the SternGerlach experiment, and in 1944, Rabi was awarded the Nobel Prize in physics for this work.[1]
In 1946, Felix Bloch and Edward Mills Purcell expanded the technique for use on liquids and solids, for which they
shared the Nobel Prize in Physics in 1952.[2]
Purcell had worked on the development of radar during World War II at the Massachusetts Institute of Technology's
Radiation Laboratory. His work during that project on the production and detection of radio frequency power and on
the absorption of such RF power by matter laid the foundation for Rabi's discovery of NMR.
Rabi, Bloch, and Purcell observed that magnetic nuclei, like 1H and 31P, could absorb RF energy when placed in a
magnetic field and when the RF was of a frequency specific to the identity of the nuclei. When this absorption
occurs, the nucleus is described as being in resonance. Different atomic nuclei within a molecule resonate at
different (radio) frequencies for the same magnetic field strength. The observation of such magnetic resonance
frequencies of the nuclei present in a molecule allows any trained user to discover essential chemical and structural
information about the molecule.
The development of NMR as a technique in analytical chemistry and biochemistry parallels the development of
electromagnetic technology and advanced electronics and their introduction into civilian use.

Theory of nuclear magnetic resonance

Nuclear spin and magnets
All nucleons, that is neutrons and protons, composing any atomic nucleus, have the intrinsic quantum property of
spin. The overall spin of the nucleus is determined by the spin quantum number S. If the number of both the protons
and neutrons in a given nuclide are even then S = 0, i.e. there is no overall spin. Then, just as electrons pair up in
atomic orbitals, so do even numbers of protons or even numbers of neutrons (which are also spin-12 particles and
hence fermions) pair up giving zero overall spin.
However, a proton and neutron will have lower energy when their spins are parallel, not anti-parallel, since this
parallel spin alignment does not infringe upon the Pauli Exclusion Principle, but instead it has to do with the quark
structure of these two nucleons. Therefore, the spin ground state for the deuteron (the deuterium nucleus, or the 2H
isotope of hydrogen)that has only a proton and a neutroncorresponds to a spin value of 1, not of zero. The
single, isolated deuteron therefore exhibits an NMR absorption spectrum characteristic of a quadrupolar nucleus of
spin 1, which in the "rigid" state at very low temperatures is a characteristic ('Pake') doublet, (not a singlet as for a
single, isolated 1H, or any other isolated fermion or dipolar nucleus of spin 1/2). On the other hand, because of the
Pauli Exclusion Principle, the tritium isotope of hydrogen must have a pair of anti-parallel spin neutrons (of total
spin zero for the neutron-spin pair), plus a proton of spin 1/2. Therefore, the character of the tritium nucleus is again
magnetic dipolar, not quadrupolarlike its non-radioactive deuteron cousinand the tritium nucleus total spin
value is again 1/2, just like for the simpler, abundant hydrogen isotope, 1H nucleus (the proton). The NMR
absorption (radio) frequency for tritium is however slightly higher than that of 1H because the tritium nucleus has a
slightly higher gyromagnetic ratio than 1H. In many other cases of non-radioactive nuclei, the overall spin is also
non-zero. For example, the 27Al nucleus has an overall spin value S = 52.
A non-zero spin is thus always associated with a non-zero magnetic moment () via the relation = S, where is
the gyromagnetic ratio. It is this magnetic moment that allows the observation of NMR absorption spectra caused by
transitions between nuclear spin levels. Most nuclides (with some rare exceptions) that have both even numbers of
protons and even numbers of neutrons, also have zero nuclear magnetic moments, and they also have zero magnetic
dipole and quadrupole moments. Hence, such nuclides do not exhibit any NMR absorption spectra. Thus, 18O is an
example of a nuclide that has no NMR absorption, whereas 13C, 31P, 35Cl and 37Cl are nuclides that do exhibit

Nuclear magnetic resonance

NMR absorption spectra. The last two nuclei are quadrupolar nuclei whereas the preceding two nuclei (13C and 31P)
are dipolar ones.
Electron spin resonance (ESR) is a related technique in which transitions between electronic spin levels are detected
rather than nuclear ones. The basic principles are similar but the instrumentation, data analysis, and detailed theory
are significantly different. Moreover, there is a much smaller number of molecules and materials with unpaired
electron spins that exhibit ESR (or electron paramagnetic resonance (EPR)) absorption than those that have NMR
absorption spectra. ESR has much higher sensitivity than NMR does.

Values of spin angular momentum

The angular momentum associated with nuclear spin is quantized. This means both that the magnitude of angular
momentum is quantized (i.e. S can only take on a restricted range of values), and also that the orientation of the
associated angular momentum is quantized. The associated quantum number is known as the magnetic quantum
number, m, and can take values from +S to S, in integer steps. Hence for any given nucleus, there are a total of 2S +
1 angular momentum states.
The z-component of the angular momentum vector (S) is therefore Sz = m, where is the reduced Planck constant.
The z-component of the magnetic moment is simply:

Spin behavior in a magnetic field

Consider nuclei which have a spin of
one-half, like 1H, 13C or 19F. The nucleus
has two possible spin states: m = 12 or m =
12 (also referred to as spin-up and
spin-down, or sometimes and spin
states, respectively). These states are
degenerate, that is they have the same
energy. Hence the number of atoms in these
two states will be approximately equal at
thermal equilibrium.
If a nucleus is placed in a magnetic field,
however, the interaction between the nuclear
Splitting of nuclei spin states in an external magnetic field
magnetic moment and the external magnetic
field mean the two states no longer have the
same energy. The energy of a magnetic moment when in a magnetic field B0 is given by:
Usually the z axis is chosen to be along B0, and the above expression reduces to:
or alternatively:

Nuclear magnetic resonance

As a result the different nuclear spin states

have different energies in a non-zero
magnetic field. In less formal language, we
can talk about the two spin states of a spin
1
2 as being aligned either with or against
the magnetic field. If is positive (true for
most isotopes) then m = 12 is the lower
energy state.
The energy difference between the two
states is:

and this difference results in a small

population bias toward the lower energy
state.

An intuitive model. Nuclei behave like they had own magnetic moments (spin
magnetic moments). By itself, there is no energetic difference for any particular
orientation (only one energy state, on the left), but in external magnetic field there
is a high-energy state and a low-energy state depending on the relative orientations
of the magnet to the external field, and the orientation of the magnetic moment can
precess relative to it. The external field can be supplied by a large magnet and also
by other nuclei in the vicinity.

Magnetic resonance by nuclei

Resonant absorption by nuclear spins will occur only when electromagnetic radiation of the correct frequency (e.g.,
equaling the Larmor precession rate) is being applied to match the energy difference between the nuclear spin levels
in a constant magnetic field of the appropriate strength. The energy of an absorbed photon is then E = h0, where 0
is the resonance radiofrequency that has to match (that is, it has to be equal to the Larmor precession frequency L of
the nuclear magnetization in the constant magnetic field B0). Hence, a magnetic resonance absorption will only
occur when E = h0, which is when 0 = B0/(2). Such magnetic resonance frequencies typically correspond to
the radio frequency (or RF) range of the electromagnetic spectrum for magnetic fields up to roughly 20T. It is this
magnetic resonant absorption which is detected in NMR. [citation needed]
Nuclear shielding
It might appear from the above that all nuclei of the same nuclide (and hence the same ) would resonate at the same
frequency. This is not the case. The most important perturbation of the NMR frequency for applications of NMR is
the "shielding" effect of the surrounding shells of electrons.[3] Electrons, similar to the nucleus, are also charged and
rotate with a spin to produce a magnetic field opposite to the magnetic field produced by the nucleus. In general, this
electronic shielding reduces the magnetic field at the nucleus (which is what determines the NMR frequency).
As a result the energy gap is reduced, and the frequency required to achieve resonance is also reduced. This shift in
the NMR frequency due to the electronic molecular orbital coupling to the external magnetic field is called chemical
shift, and it explains why NMR is able to probe the chemical structure of molecules, which depends on the electron
density distribution in the corresponding molecular orbitals. If a nucleus in a specific chemical group is shielded to a
higher degree by a higher electron density of its surrounding molecular orbital, then its NMR frequency will be
shifted "upfield" (that is, a lower chemical shift), whereas if it is less shielded by such surrounding electron density,
then its NMR frequency will be shifted "downfield" (that is, a higher chemical shift).
Unless the local symmetry of such molecular orbitals is very high (leading to "isotropic" shift), the shielding effect
will depend on the orientation of the molecule with respect to the external field (B0). In solid-state NMR
spectroscopy, magic angle spinning is required to average out this orientation dependence in order to obtain values
close to the average chemical shifts. This is unnecessary in conventional NMR investigations of molecules, since
rapid "molecular tumbling" averages out the chemical shift anisotropy (CSA). In this case, the term "average"
chemical shift (ACS) is used.

Nuclear magnetic resonance

Relaxation
The process called population relaxation refers to nuclei that return to the thermodynamic state in the magnet. This
process is also called T1, "spin-lattice" or "longitudinal magnetic" relaxation, where T1 refers to the mean time for an
individual nucleus to return to its thermal equilibrium state of the spins. Once the nuclear spin population is relaxed,
it can be probed again, since it is in the initial, equilibrium (mixed) state.
The precessing nuclei can also fall out of alignment with each other (returning the net magnetization vector to a
non-precessing field) and stop producing a signal. This is called T2 or transverse relaxation. Because of the
difference in the actual relaxation mechanisms involved (for example, inter-molecular vs. intra-molecular magnetic
dipole-dipole interactions ), T1 is usually (except in rare cases) longer than T2 (that is, slower spin-lattice relaxation,
for example because of smaller dipole-dipole interaction effects). In practice, the value of
which is the actually
observed decay time of the observed NMR signal, or free induction decay, (to 1/e of the initial amplitude
immediately after the resonant RF pulse)-- also depends on the static magnetic field inhomogeneity, which is quite
significant. (There is also a smaller but significant contribution to the observed FID shortening from the RF
inhomogeneity of the resonant pulse). In the corresponding FT-NMR spectrummeaning the Fourier transform of
the free induction decaythe
time is inversely related to the width of the NMR signal in frequency units. Thus,
a nucleus with a long T2 relaxation time gives rise to a very sharp NMR peak in the FT-NMR spectrum for a very
homogeneous ("well-shimmed") static magnetic field, whereas nuclei with shorter T2 values give rise to broad
FT-NMR peaks even when the magnet is shimmed well. Both T1 and T2 depend on the rate of molecular motions as
well as the gyromagnetic ratios of both the resonating and their strongly interacting, next-neighbor nuclei that are not
at resonance.
A Hahn echo decay experiment can be used to measure the dephasing time, as shown in the animation below. The
size of the echo is recorded for different spacings of the two pulses. This reveals the decoherence which is not
refocused by the pulse. In simple cases, an exponential decay is measured which is described by the
time.

Nuclear magnetic resonance

NMR spectroscopy
NMR spectroscopy is one of the principal
techniques used to obtain physical, chemical,
electronic and structural information about
molecules due to either the chemical shift, Zeeman
effect, or the Knight shift effect, or a combination
of both, on the resonant frequencies of the nuclei
present in the sample. It is a powerful technique
that can provide detailed information on the
topology, dynamics and three-dimensional
structure of molecules in solution and the solid
state. Thus, structural and dynamic information is
obtainable (with or without "magic angle" spinning
(MAS)) from NMR studies of quadrupolar nuclei
(that is, those nuclei with spin S > 12) even in the
presence of magnetic "dipole-dipole" interaction
broadening (or simply, dipolar broadening) which
is always much smaller than the quadrupolar
interaction strength because it is a magnetic vs. an
electric interaction effect.
Additional structural and chemical information
900 MHz, 21.2T NMR Magnet at HWB-NMR, Birmingham, UK
may be obtained by performing double-quantum
NMR experiments for quadrupolar nuclei such as
2H. Also, nuclear magnetic resonance is one of the techniques that has been used to design quantum automata, and
also build elementary quantum computers.[4]

Continuous wave (CW) spectroscopy

In its first few decades, nuclear magnetic resonance spectrometers used a technique known as continuous-wave
spectroscopy (CW spectroscopy). Although NMR spectra could be, and have been, obtained using a fixed magnetic
field and sweeping the frequency of the electromagnetic radiation, this more typically involved using a fixed
frequency source and varying the current (and hence magnetic field) in an electromagnet to observe the resonant
absorption signals. This is the origin of the counterintuitive, but still common, "high field" and "low field"
terminology for low frequency and high frequency regions respectively of the NMR spectrum.
CW spectroscopy is inefficient in comparison with Fourier analysis techniques (see below) since it probes the NMR
response at individual frequencies in succession. Since the NMR signal is intrinsically weak, the observed spectrum
suffers from a poor signal-to-noise ratio. This can be mitigated by signal averaging i.e. adding the spectra from
repeated measurements. While the NMR signal is constant between scans and so adds linearly, the random noise
adds more slowly proportional to the square-root of the number of spectra (see random walk). Hence the overall
signal-to-noise ratio increases as the square-root of the number of spectra measured.

Nuclear magnetic resonance

Fourier transform spectroscopy

Most applications of NMR involve full NMR spectra, that is, the intensity of the NMR signal as a function of
frequency. Early attempts to acquire the NMR spectrum more efficiently than simple CW methods involved
illuminating the target simultaneously with more than one frequency. A revolution in NMR occurred when short
pulses of radio-frequency radiation began to be usedcentered at the middle of the NMR spectrum. In simple terms,
a short pulse of a given "carrier" frequency "contains" a range of frequencies centered about the carrier frequency,
with the range of excitation (bandwidth) being inversely proportional to the pulse duration, i.e. the Fourier transform
of a short pulse contains contributions from all the frequencies in the neighborhood of the principal frequency. The
restricted range of the NMR frequencies made it relatively easy to use short (millisecond to microsecond) radio
frequency pulses to excite the entire NMR spectrum.[citation needed]
Applying such a pulse to a set of nuclear spins simultaneously excites all the single-quantum NMR transitions. In
terms of the net magnetization vector, this corresponds to tilting the magnetization vector away from its equilibrium
position (aligned along the external magnetic field). The out-of-equilibrium magnetization vector precesses about the
external magnetic field vector at the NMR frequency of the spins. This oscillating magnetization vector induces a
current in a nearby pickup coil, creating an electrical signal oscillating at the NMR frequency. This signal is known
as the free induction decay (FID), and it contains the vector sum of the NMR responses from all the excited spins. In
order to obtain the frequency-domain NMR spectrum (NMR absorption intensity vs. NMR frequency) this
time-domain signal (intensity vs. time) must be Fourier transformed. Fortunately the development of Fourier
Transform NMR coincided with the development of digital computers and the digital Fast Fourier Transform.
Fourier methods can be applied to many types of spectroscopy. (See the full article on Fourier transform
spectroscopy.)
Richard R. Ernst was one of the pioneers of pulse NMR, and he won a Nobel Prize in chemistry in 1991 for his work
on Fourier Transform NMR and his development of multi-dimensional NMR (see below).

Multi-dimensional NMR Spectroscopy

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. 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 systematically varied. In multidimensional nuclear magnetic resonance
there will be a sequence of pulses and, at least, one variable time period. In three dimensions, two time sequences
will be varied. In four dimensions, three will be varied.
There are many such experiments. In one, these time intervals allow (amongst other things) magnetization transfer
between nuclei and, therefore, the detection of the kinds of nuclear-nuclear interactions that allowed for the
magnetization transfer. Interactions that can be detected are usually classified into two kinds. 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 be employed to establish distances between
atoms, as for example by 2D-FT NMR of molecules in solution.
Although the fundamental concept of 2D-FT NMR was proposed by Jean Jeener from the Free University of
Brussels at an International Conference, this idea was largely developed by Richard Ernst who won the 1991 Nobel
prize in Chemistry for his work in FT NMR, including multi-dimensional FT NMR, and especially 2D-FT NMR of
small molecules.[5] Multi-dimensional FT NMR experiments were then further developed into powerful
methodologies for studying biomolecules in solution, in particular for the determination of the structure of
biopolymers such as proteins or even small nucleic acids.
In 2002 Kurt Wthrich shared the Nobel Prize in Chemistry (with John Bennett Fenn and Koichi Tanaka) for his
work with protein FT NMR in solution.

Nuclear magnetic resonance

Solid-state NMR spectroscopy

This technique complements X-ray crystallography in that it is frequently applicable to molecules in a liquid or
liquid crystal phase, whereas crystallography, as the name implies, is performed on molecules in a solid phase.
Though nuclear magnetic resonance is used to study solids, extensive atomic-level molecular structural detail is
especially challenging to obtain in the solid state. There is little signal averaging by thermal motion in the solid state,
where most molecules can only undergo restricted vibrations and rotations at room temperature, each in a slightly
different electronic environment, therefore exhibiting a different NMR absorption peak. Such a variation in the
electronic environment of the resonating nuclei results in a blurring of the observed spectrawhich is often only a
broad Gaussian band for non-quadrupolar spins in a solid- thus making the interpretation of such "dipolar" and
"chemical shift anisotropy" (CSA) broadened spectra either very difficult or impossible.
Professor Raymond Andrew at Nottingham University in the UK pioneered the development of high-resolution
solid-state nuclear magnetic resonance. He was the first to report the introduction of the MAS (magic angle sample
spinning; MASS) technique that allowed him to achieve spectral resolution in solids sufficient to distinguish between
chemical groups with either different chemical shifts or distinct Knight shifts. In MASS, the sample is spun at
several kilohertz around an axis that makes the so-called magic angle m (which is ~54.74, where cos2m = 1/3)
with respect to the direction of the static magnetic field B0; as a result of such magic angle sample spinning, the
chemical shift anisotropy bands are averaged to their corresponding average (isotropic) chemical shift values. The
above expression involving cos2m has its origin in a calculation that predicts the magnetic dipolar interaction effects
to cancel out for the specific value of m called the magic angle. One notes that correct alignment of the sample
rotation axis as close as possible to m is essential for cancelling out the dipolar interactions whose strength for
angles sufficiently far from m is usually greater than ~10kHz for C-H bonds in solids, for example, and it is thus
greater than their CSA values.
There are different angles for the sample spinning relative to the applied field for the averaging of quadrupole
interactions and paramagnetic interactions, correspondingly ~30.6 and ~70.1
A concept developed by Sven Hartmann and Erwin Hahn was utilized in transferring magnetization from protons to
less sensitive nuclei (popularly known as cross-polarization) by M.G. Gibby, Alex Pines and John S. Waugh. Then,
Jake Schaefer and Ed Stejskal demonstrated also the powerful use of cross-polarization under MASS conditions
which is now routinely employed to detect low-abundance and low-sensitivity nuclei.

Sensitivity
Because the intensity of nuclear magnetic resonance signals and, hence, the sensitivity of the technique depends 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 audio-visual technology have also improved the signal-generation and
processing capabilities of newer instruments.
As noted above, the sensitivity of nuclear magnetic resonance signals is also dependent 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 example) are both magnetically susceptible and readily useful
for nuclear magnetic resonance spectroscopy. In contrast, carbon and nitrogen have useful isotopes but which occur
only in very low natural abundance.
Other limitations on sensitivity arise from the quantum-mechanical nature of the phenomenon. For quantum states
separated by energy equivalent to radio frequencies, thermal energy from the environment causes the populations of
the states to be close to equal. Since incoming radiation is equally likely to cause stimulated emission (a transition
from the upper to the lower state) as absorption, the NMR effect depends on an excess of nuclei in the lower states.
Several factors can reduce sensitivity, including

Nuclear magnetic resonance

Increasing temperature, which evens out the population of states. Conversely, low temperature NMR can
sometimes yield better results than room-temperature NMR, providing the sample remains liquid.
Saturation of the sample with energy applied at the resonant radiofrequency. This manifests in both CW and
pulsed NMR; in the first case (CW) this happens by using too much continuous power that keeps the upper spin
levels completely populated; in the second case (pulsed), each pulse (that is at least a 90 pulse) leaves the sample
saturated, and four to five times the (longitudinal) relaxation time (5 T1) must pass before the next pulse or pulse
sequence can be applied. For single pulse experiments, shorter RF pulses that tip the magnetization by less than
90 can be used, which loses some intensity of the signal, but allows for shorter recycle delays. The optimum
there is called an Ernst angle, after the Nobel laureate. Especially in solid state NMR, or in samples with very few
nuclei with spins > 0, (diamond with the natural 1% of Carbon-13 is especially troublesome here) the longitudinal
relaxation times can be on the range of hours, while for proton-NMR they are more on the range of one second.
Non-magnetic effects, such as electric-quadrupole coupling of spin-1 and spin-32 nuclei with their local
environment, which broaden and weaken absorption peaks. 14N, an abundant spin-1 nucleus, is difficult to study
for this reason. High resolution NMR instead probes molecules using the rarer 15N isotope, which has spin-12.

Isotopes
Many isotopes of chemical elements can be used for NMR analysis.[6]
Commonly used nuclei:
1H, the most commonly used spin nucleus in NMR investigation, has been studied using many forms of NMR.
Hydrogen is highly abundant, especially in biological systems. It is the nucleus most sensitive to NMR signal
(apart from 3H which is not commonly used due to its instability and radioactivity). Proton NMR produces
narrow chemical shift with sharp signals. Fast acquisition of quantitative results (peak integrals in stoichiometric
ratio) is possible due to short relaxation time. The 1H signal has been the sole diagnostic nucleus used for clinical
magnetic resonance imaging.
2H, a spin 1 nucleus commonly utilized as signal-free medium in the form of deuterated solvents during proton
NMR, to avoid signal interference from hydrogen-containing solvents in measurement of 1H solutes. Also used in
determining the behavior of lipids in lipid membranes and other solids or liquid crystals as it is a relatively
non-perturbing label which can selectively replace 1H. Alternatively, 2H can be detected in media specially
labeled with 2H. Deuterium resonance is commonly used in high-resolution NMR spectroscopy to monitor drifts
in the magnetic field strength (lock) and to improve the homogeneity of the external magnetic field.
3He, is very sensitive to NMR. There is a very low percentage in natural helium, and subsequently has to be
purified from 4He. It is used mainly in studies of endohedral fullerenes, where its chemical inertness is beneficial
to ascertaining the structure of the entrapping fullerene.
11B, more sensitive than 10B, yields sharper signals. Quartz tubes must be used as borosilicate glass interferes
with measurement.
13C spin-1/2, is widely used, despite its relative paucity in naturally occurring carbon (approximately 1%). It is
stable to nuclear decay. Since there is a low percentage in natural carbon, spectrum acquisition on samples which
have not been experimentally enriched in 13C takes a long time. Frequently used for labeling of compounds in
synthetic and metabolic studies. Has low sensitivity and wide chemical shift, yields sharp signals. Low percentage
makes it useful by preventing spin-spin couplings and makes the spectrum appear less crowded. Slow relaxation
means that spectra are not integrable unless long acquisition times are used.
14N, spin-1, medium sensitivity nucleus with wide chemical shift. Its large quadrupole moment interferes in
acquisition of high resolution spectra, limiting usefulness to smaller molecules and functional groups with a high
degree of symmetry such as the headgroups of lipids.
15N, spin-1/2, relatively commonly used. Can be used for labeling compounds. Nucleus very insensitive but
yields sharp signals. Low percentage in natural nitrogen together with low sensitivity requires high concentrations
or expensive isotope enrichment.

Nuclear magnetic resonance

17O, spin-5/2, low sensitivity and very low natural abundance (0.037%), wide chemical shifts range (up to 2000
ppm). Quadrupole moment causing a line broadening. Used in metabolic and biochemical studies in studies of
chemical equilibria.
19F, spin-1/2, relatively commonly measured. Sensitive, yields sharp signals, has wide chemical shift.
31P, spin-1/2, 100% of natural phosphorus. Medium sensitivity, wide chemical shifts range, yields sharp lines.
Spectra tend to have a moderate amount of noise. Used in biochemical studies and in coordination chemistry
where phosphorus containing ligands are involved.
35Cl and 37Cl, broad signal. 35Cl significantly more sensitive, preferred over 37Cl despite its slightly broader
signal. Organic chlorides yield very broad signals, its use is limited to inorganic and ionic chlorides and very
small organic molecules.
43Ca, used in biochemistry to study calcium binding to DNA, proteins, etc. Moderately sensitive, very low natural
abundance.
113Cd, used to study metal-binding in metallothioneins and alkaline phosphatase and other metalloproteins.
195Pt, used in studies of catalysts and complexes.
Other nuclei (usually used in the studies of their complexes and chemical binding, or to detect presence of the
element):
6Li, 7Li

9Be
19F
21Ne
23Na
25Mg
27Al
29Si
31P
33S
39K, 40K, 41K
45Sc
47Ti, 49Ti
50V, 51V
53Cr
55Mn
57Fe
59Co
61Ni
63Cu, 65Cu
67Zn
69Ga, 71Ga
73Ge
75As
77Se
81Br
87Rb
87Sr

95Mo
109Ag
119Sn

10

Nuclear magnetic resonance

125Te
127I
133Cs
135Ba, 137Ba
139La
183W
199Hg

Applications
Medicine
The application of nuclear magnetic resonance best known to the
general public is magnetic resonance imaging for medical diagnosis
and magnetic resonance microscopy in research settings, however, it is
also widely used in chemical studies, notably in NMR spectroscopy
such as proton NMR, carbon-13 NMR, deuterium NMR and
phosphorus-31 NMR. Biochemical information can also be obtained
from living tissue (e.g. human brain tumors) with the technique known
as in vivo magnetic resonance spectroscopy or chemical shift NMR
Microscopy.
These studies are possible because nuclei are surrounded by orbiting
Medical MRI
electrons, which are charged particles that generate small, local
magnetic fields that add to or subtract from the external magnetic field,
and so will partially shield the nuclei. The amount of shielding depends on the exact local environment. For example,
a hydrogen bonded to an oxygen will be shielded differently than a hydrogen bonded to a carbon atom. In addition,
two hydrogen nuclei can interact via a process known as spin-spin coupling, if they are on the same molecule, which
will split the lines of the spectra in a recognizable way.
As one of the two major spectroscopic techniques used in metabolomics, NMR is used to generate metabolic
fingerprints from biological fluids to obtain information about disease states or toxic insults.

Chemistry
By studying the peaks of nuclear magnetic resonance spectra, chemists can determine the structure of many
compounds. It can be a very selective technique, distinguishing among many atoms within a molecule or collection
of molecules of the same type but which differ only in terms of their local chemical environment. NMR spectroscopy
is used to unambiguously identify known and novel compounds, and as such, is usually required by scientific
journals for identity confirmation of synthesized new compounds. See the articles on carbon-13 NMR and proton
NMR for detailed discussions.
By studying T2 information, a chemist can determine the identity of a compound by comparing the observed nuclear
precession frequencies to known frequencies. Further structural data can be elucidated by observing spin-spin
coupling, a process by which the precession frequency of a nucleus can be influenced by the magnetization transfer
from nearby chemically bound nuclei. Spin-spin coupling is observed in NMR of hydrogen-1 (1H NMR), since its
natural abundance is nearly 100%; isotope enrichment is required for most other elements.
Because the nuclear magnetic resonance timescale is rather slow, compared to other spectroscopic methods,
changing the temperature of a T2*experiment can also give information about fast reactions, such as the Cope
rearrangement or about structural dynamics, such as ring-flipping in cyclohexane. At low enough temperatures, a

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Nuclear magnetic resonance

distinction can be made between the axial and equatorial hydrogens in cyclohexane.
An example of nuclear magnetic resonance being used in the determination of a structure is that of
buckminsterfullerene (often called "buckyballs", composition C60). This now famous form of carbon has 60 carbon
atoms forming a sphere. The carbon atoms are all in identical environments and so should see the same internal H
field. Unfortunately, buckminsterfullerene contains no hydrogen and so 13C nuclear magnetic resonance has to be
used. 13C spectra require longer acquisition times since carbon-13 is not the common isotope of carbon (unlike
hydrogen, where 1H is the common isotope). However, in 1990 the spectrum was obtained by R. Taylor and
co-workers at the University of Sussex and was found to contain a single peak, confirming the unusual structure of
buckminsterfullerene.

Purity determination (w/w NMR)

NMR is primarily used for structural determination, however it can also be used for purity determination, providing
that the structure and molecular weight of the compound is known. This technique requires the use of an internal
standard of a known purity. Typically this standard will have a high molecular weight to facilitate accurate weighing,
but relatively few protons so as to give a clear peak for later integration e.g. 1,2,3,4-tetrachloro-5-nitrobenzene.
Accurately weighed portions of both the standard and sample are combined and analysed by NMR. Suitable peaks
are selected for both compounds and the purity of the sample determined via the following equation.

Where:
: Weight of internal standard
: Weight of sample
: The integrated area of the peak selected for comparison in the standard, corrected for the
number of protons in that functional group
: The integrated area of the peak selected for comparison in the sample, corrected for the number
of protons in that functional group
: Molecular weight of standard
: Molecular weight of sample
: Purity of internal standard

Non-destructive testing
Nuclear magnetic resonance is extremely useful for analyzing samples non-destructively. Radio waves and static
magnetic fields easily penetrate many types of matter and anything that is not inherently ferromagnetic. For example,
various expensive biological samples, such as nucleic acids, including RNA and DNA, or proteins, can be studied
using nuclear magnetic resonance for weeks or months before using destructive biochemical experiments. This also
makes nuclear magnetic resonance a good choice for analyzing dangerous samples.

Acquisition of dynamic information

In addition to providing static information on molecules by determining their 3D structures in solution, one of the
remarkable advantages of NMR over X-ray crystallography is that it can be used to obtain important dynamic
information including the low-frequency collective motion in proteins and DNA, for example in the Ca2+-calmodulin
system. The low-frequency internal motion in biomacromolecules and its biological functions have been discussed
by Chou.

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Data acquisition in the petroleum industry

Another use for nuclear magnetic resonance is data acquisition in the petroleum industry for petroleum and natural
gas exploration and recovery. A borehole is drilled into rock and sedimentary strata into which nuclear magnetic
resonance logging equipment is lowered. Nuclear magnetic resonance analysis of these boreholes is used to measure
rock porosity, estimate permeability from pore size distribution and identify pore fluids (water, oil and gas). These
instruments are typically low field NMR spectrometers.

Flow probes for NMR spectroscopy

Recently, real-time applications of NMR in liquid media have been developed using specifically designed flow
probes (flow cell assemblies) which can replace standard tube probes. This has enabled techniques that can
incorporate the use of high performance liquid chromatography (HPLC) or other continuous flow sample
introduction devices.

Process control
NMR has now entered the arena of real-time process control and process optimization in oil refineries and
petrochemical plants. Two different types of NMR analysis are utilized to provide real time analysis of feeds and
products in order to control and optimize unit operations. Time-domain NMR (TD-NMR) spectrometers operating at
low field (220MHz for 1H) yield free induction decay data that can be used to determine absolute hydrogen
content values, rheological information, and component composition. These spectrometers are used in mining,
polymer production, cosmetics and food manufacturing as well as coal analysis. High resolution FT-NMR
spectrometers operating in the 60MHz range with shielded permanent magnet systems yield high resolution 1H
NMR spectra of refinery and petrochemical streams. The variation observed in these spectra with changing physical
and chemical properties is modeled using chemometrics to yield predictions on unknown samples. The prediction
results are provided to control systems via analogue or digital outputs from the spectrometer.

Earth's field NMR

In the Earth's magnetic field, NMR frequencies are in the audio frequency range, or the very low frequency and ultra
low frequency bands of the radio frequency spectrum. Earth's field NMR (EFNMR) is typically stimulated by
applying a relatively strong dc magnetic field pulse to the sample and, after the end of the pulse, analyzing the
resulting low frequency alternating magnetic field that occurs in the Earth's magnetic field due to free induction
decay (FID). These effects are exploited in some types of magnetometers, EFNMR spectrometers, and MRI imagers.
Their inexpensive portable nature makes these instruments valuable for field use and for teaching the principles of
NMR and MRI.
An important feature of EFNMR spectrometry compared with high-field NMR is that some aspects of molecular
structure can be observed more clearly at low fields and low frequencies, whereas other aspects observable at high
fields are not observable at low fields. This is because:
Electron-mediated heteronuclear J-couplings (spin-spin couplings) are field independent, producing clusters of
two or more frequencies separated by several Hz, which are more easily observed in a fundamental resonance of
about 2 kHz. "Indeed it appears that enhanced resolution is possible due to the long spin relaxation times and high
field homogeneity which prevail in EFNMR."
Chemical shifts of several ppm are clearly separated in high field NMR spectra, but have separations of only a
few millihertz at proton EFNMR frequencies, so are usually lost in noise etc.

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Nuclear magnetic resonance

Quantum computing
NMR quantum computing uses the spin states of molecules as qubits. NMR differs from other implementations of
quantum computers in that it uses an ensemble of systems, in this case molecules.

Magnetometers
Various magnetometers use NMR effects to measure magnetic fields, including proton precession magnetometers
(PPM) (also known as proton magnetometers), and Overhauser magnetometers. See also Earth's field NMR.

Makers of NMR equipment

Major NMR instrument makers include Oxford Instruments, Bruker, Spinlock SRL, General Electric, JEOL, Kimble
Chase, Philips, Siemens AG, and Agilent Technologies, Inc. (who own Varian, Inc.).

References
[1] Biography of I. Rabi at Nobelprize.org (http:/ / nobelprize. org/ nobel_prizes/ physics/ laureates/ 1944/ rabi-bio. html)
[2] 1952 Nobel Prize for Physics at Nobelprize.org (http:/ / nobelprize. org/ nobel_prizes/ physics/ laureates/ 1952/ )
[3] Principle of Shielding and Deshielding | NMRCentral.com (http:/ / nmrcentral. com/ 2011/ 08/ principle-of-shielding-and-deshielding/ )
[4] Quantum automaton and quantum computation (http:/ / planetphysics. org/ encyclopedia/ QuantumComputers. html) (see also references
therein)
[5] "Nuclear Magnetic Resonance Fourier Transform Spectroscopy" (http:/ / nobelprize. org/ nobel_prizes/ chemistry/ laureates/ 1991/
ernst-lecture. html) Ernst's Nobel lecture. (Includes mention of Jeener's suggestion.)
[6] Multinuclear NMR (http:/ / chem. ch. huji. ac. il/ nmr/ techniques/ 1d/ multi. html)

Further reading
Gary E. Martin, A. S. Zektzer (1988). Two-Dimensional NMR Methods for Establishing Molecular Connectivity
(http://books.google.com/books?id=9ysYrpe_NoEC&printsec=frontcover). New York: Wiley-VCH. p.59.
ISBN0-471-18707-0.
J.W. Akitt, B.E. Mann (2000). NMR and Chemistry. Cheltenham, UK: Stanley Thornes. pp.273, 287.
ISBN0-7487-4344-8.
J.P. Hornak. "The Basics of NMR" (http://www.cis.rit.edu/htbooks/nmr/). Retrieved 2009-02-23.
J. Keeler (2005). Understanding NMR Spectroscopy. John Wiley & Sons. ISBN0-470-01786-4.
Kurt Wthrich (1986). NMR of Proteins and Nucleic Acids. New York (NY), USA: Wiley-Interscience.
ISBN0-471-11917-2.
J.M Tyszka, S.E Fraser, R.E Jacobs (2005). "Magnetic resonance microscopy: recent advances and applications".
Current Opinion in Biotechnology 16 (1): 9399. doi: 10.1016/j.copbio.2004.11.004 (http://dx.doi.org/10.
1016/j.copbio.2004.11.004). PMID 15722021 (http://www.ncbi.nlm.nih.gov/pubmed/15722021).
J.C. Edwards. "Principles of NMR" (http://www.process-nmr.com/pdfs/NMR Overview.pdf). Process NMR
Associates. Retrieved 2009-02-23.
R.L Haner, P.A. Keifer (2009). Encyclopedia of Magnetic Resonance. John Wiley. doi:
10.1002/9780470034590.emrstm1085 (http://dx.doi.org/10.1002/9780470034590.emrstm1085).

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Nuclear magnetic resonance

External links
Tutorial
NMR/MRI tutorial (http://www.cis.rit.edu/htbooks/nmr/inside.htm)
NMR Library (http://nmr.chinanmr.cn/guide/eNMR/eNMRindex.html) NMR Concepts
NMR Course Notes (http://www.grandinetti.org/Teaching/Chem7160/Notes)

Animations and Simulations

This animation shows a spin, the modification of spin with magnetic field and HF pulse, spin echo sequences,
inversion recovery sequence, gradient echo sequence and relaxation of spin (http://www.bigs.de/BLH/en/
index.php?option=com_content&view=category&layout=blog&id=51&Itemid=222)
Animation of NMR spin 12 precession (http://www.chem.queensu.ca/FACILITIES/NMR/nmr/webcourse/
precess.htm)
A free interactive simulation of NMR principles (http://vam.anest.ufl.edu/forensic/nmr.html)

Video
introduction to NMR and MRI (http://www.youtube.com/watch?v=7aRKAXD4dAg)
Richard Ernst, NL Developer of Multdimensional NMR techniques (http://www.vega.org.uk/video/
programme/21) Freeview video provided by the Vega Science Trust.
'An Interview with Kurt Wuthrich' (http://www.vega.org.uk/video/programme/115) Freeview video by the
Vega Science Trust (Wthrich was awarded a Nobel Prize in Chemistry in 2002 "for his development of nuclear
magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in
solution").
Other
Off Magic Angle Spinning (http://www.sciencedirect.com/science/article/pii/S109078070700198X)

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Article Sources and Contributors

Article Sources and Contributors

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Image Sources, Licenses and Contributors

File:700 lab fix.JPG Source: http://en.wikipedia.org/w/index.php?title=File:700_lab_fix.JPG License: Public Domain Contributors: Mike25
Image:NMR splitting.gif Source: http://en.wikipedia.org/w/index.php?title=File:NMR_splitting.gif License: Public domain Contributors: Gsrdzl, Magog the Ogre
Image:NMR EPR.gif Source: http://en.wikipedia.org/w/index.php?title=File:NMR_EPR.gif License: Creative Commons Attribution-Sharealike 3.0 Contributors: User:Darekk2
Image:HWB-NMR - 900MHz - 21.2 Tesla.jpg Source: http://en.wikipedia.org/w/index.php?title=File:HWB-NMR_-_900MHz_-_21.2_Tesla.jpg License: Public Domain Contributors:
Original uploader was MartinSaunders at en.wikipedia
File:MRI-Philips.JPG Source: http://en.wikipedia.org/w/index.php?title=File:MRI-Philips.JPG License: Creative Commons Attribution 3.0 Contributors: Jan Ainali

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