NMR Spectroscopy Principles, Interpreting an NMR Spectrum and Common Problems
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Nuclear magnetic resonance (NMR) spectroscopy is a physicochemical technique used to obtain structural information about molecules. It is based on the physical phenomenon of magnetic resonance that was first demonstrated by Isidor I. Rabi in 1938. In the 1940s, two research groups independently obtained the first successful measurements of NMR in condensed matter. The two principal investigators of these groups, Felix Bloch from Stanford University and Edward M. Purcell from Harvard University, were jointly awarded with the Nobel Prize in Physics in 1952 for their contributions to the field of magnetic resonance.1,2,3
Since those early days, NMR spectroscopy progressed concurrently with advances in many other fields, such as mathematics, physics and informatics. In the 1960s, the implementation of superconducting magnets and computers to NMR equipment opened the door to a great improvement in sensitivity and the possibility to design new types of NMR experiments. As a consequence, scientists have developed a myriad of novel methodologies to study complex systems, such as membrane proteins, metabolically complex samples, or even biological tissues. NMR spectroscopy has become one of the most powerful techniques for structural determination of chemical species, as well as for the study of molecular dynamics and interactions.4,5
How does NMR work?
How to read an NMR spectrum and what it tells you
Upfield vs downfield NMR
Proton NMR vs carbon NMR
- 2D NMR
- Solid-state NMR
Strengths and weaknesses of NMR and common problems
- NMR impurities
- NMR solvent peaks
Applications of NMR
- NMR applications in chemistry
- NMR applications in the life sciences
What is NMR?
NMR spectroscopy is a physicochemical analysis technique that is based on the interaction of an externally applied radiofrequency radiation with atomic nuclei. During this interaction there is a net exchange of energy which leads to a change in an intrinsic property of the atomic nuclei called nuclear spin.
The nuclear spin is defined by a quantic number (I), which varies depending on the considered isotope. Only atomic nuclei with I ≠ 0 are detectable by NMR spectroscopy (NMR-active nuclei, such as 1H, 2H, 13C and 15N). These NMR-active nuclei behave as tiny magnets (magnetic dipoles), capable of aligning with external magnetic fields (a process called magnetization). The force of those tiny magnets is defined by a constant known as the magnetogyric ratio (γ), whose value depends on the isotope. 6,7
Nuclear spins of some NMR-active nuclei are able to adopt two different orientations when they align to an external magnetic field (B0). One orientation corresponds to the lowest energy level of the nucleus (parallel to the external magnetic field), and the other one is associated to the highest energy level of the nucleus (antiparallel to the external magnetic field) (Figure 1, left panel). The difference between energy levels (ΔE) depends on the magnetic field and the magnetogyric ratio (Eq. 1) and affects the sensitivity of the technique (Figure 1, right panel). 6,7
Magnetic resonance is achieved when nuclei are irradiated with radiofrequency. This causes transitions between energy levels, which involves changes in the orientation of nuclear spins.
When atomic nuclei are under the effect of a magnetic field, nuclear magnetic dipoles are not statically aligned with the magnetic field B0, but rather move like a spinning top (precession movement) around an axis parallel to the direction of the field (Figure 2, left panel). The frequency of this precession movement, called Larmor frequency (νL), is defined by the magnetogyric ratio and the magnetic field: 6,7
As a consequence of this precession movement, the magnetic vector (μ) associated with the nuclear magnetic dipoles possesses a component parallel to the magnetic field (μz) and another component perpendicular to the magnetic field (μxy), with this last one having a net value of zero in the absence of external perturbations. In an NMR experiment, it is not possible to measure the signal in the z direction, as the magnetic field is too intense in that direction. Therefore, it is necessary to transfer the magnetization of the z component to the xy plane. For this purpose, a magnetic pulse containing frequencies close to the Larmor frequency is applied perpendicular to B0 to reach the resonance of nuclear spins, which generates a non-zero μxy component. After this pulse, a relaxation process takes place and the μxy component gradually recovers its net value of zero (Figure 2, right panel). As a consequence of this relaxation, energy is emitted as radiofrequency, producing a characteristic signal called free induction decay (FID) which is registered by the detector. This FID is subsequently transformed into a plot of intensities versus frequencies known as an NMR spectrum. 6,7
How does NMR work?
NMR spectrometers consist of three main components: a superconducting magnet, a probe and a complex electronic system (console) controlled by a workstation (Figure 3).
Figure 3: General design of an NMR spectrometer with its principal components.
The magnet is responsible for the generation of a strong magnetic field that aligns the nuclear spins of the atoms present in the sample. Nowadays, the magnets used in NMR spectroscopy are based on superconducting materials, and thus, they require very low temperatures to work (around 4 K). For this reason, NMR spectrometers contain a cooling system composed of an inner jacket filled with liquid helium which is refrigerated by an additional jacket filled with liquid nitrogen, and many layers of thermal isolating materials (Figure 4).6,8
The superconducting magnet surrounds a cylindrical chamber known as the “probe”, which is a crucial component of the instrument. The sample is introduced into the probe and thus placed under the influence of the magnetic field. Additionally, the probe contains a series of magnetic coils that are also located around the sample (Figure 4). These coils have multiple purposes. On one hand, they are used to irradiate the radiofrequency pulses and to detect and collect the NMR signal emitted by the sample. On the other hand, they also enable control of the magnetic field homogeneity and the application of pulse gradients that are used in some NMR experiments. 6,8
Figure 4: Internal components of an NMR spectrometer, including a detailed view of the probe. Credit: KissCC0.
Finally, the electronic system of the spectrometer controls all the experimental conditions and enables the set up and modification of every parameter of the NMR experiment through the workstation. This system is also responsible for data acquisition and subsequent mathematical transformation into an NMR spectrum. The spectrum contains a series of peaks of different intensities as a function of a magnitude known as the chemical shift that is derived from the Larmor frequency of the different atomic nuclei present in the sample. 6,8
How to read an NMR spectrum and what it tells you
The signal detected by an NMR spectrometer (the FID) must be transformed prior to analysis. As the Larmor frequency is dependent upon the intensity of the magnetic field, it varies from instrument to instrument. For this reason, a mathematical transformation is performed to provide a relative magnitude called chemical shift (δ) (see Eq. 3). Unlike the Larmor frequency, this magnitude is independent of the magnetic field and the value can be compared across instruments. 6,7,8
Where νL is the observed Larmor frequency of a nucleus and νL0 is the Larmor frequency of a reference nucleus, both in Hz. By convention, chemical shift is always expressed in parts per million (ppm). The zero value of the chemical shift scale is set using a reference compound (such as tetramethylsilane (TMS) or sodium trimethylsilylpropanesulfonate (DSS) for 1H).
Figure 5 provides an example of a proton (1H) NMR spectrum, meaning that only the protons of the molecule are detected.
An NMR spectrum provides a lot of information about the molecules present in the sample. First, chemical groups within a molecule can be identified from chemical shift values. In the example provided in Figure 5, acetic acid (H3C-COOH) has four protons so you could be forgiven for expecting to see four signals in the spectrum. However, the three protons of the methyl group (CH3) are magnetically equivalent and therefore have the same chemical shift. This means that one signal comes from the CH3 group and the other one, from the proton in the carboxylic acid group (COOH). Secondly, in 1H-NMR spectra, signal area is proportional to the number of atomic nuclei producing that signal (this does not apply to 13C-NMR spectra). In this example, if the areas of both signals were to be calculated, the most intense signal will be three times larger than the other. This is in accordance with the fact that one signal represents the three protons from the CH3 group (signal at δ = 2.0 ppm) and the other one the proton from the COOH group (signal at δ = 11.5 ppm).9,10
The spins of two nuclei that are connected through a few chemical bonds can interact, causing a phenomenon known as scalar coupling which splits the signals. Typically, this coupling is only observable when the number of chemical bonds separating two nuclei does not exceed four. The splitting of the signals follows a pattern that depends on the number of coupled nuclei and on a coupling constant (J) defined by the type of nuclei and the distance (in chemical bonds) between them. The characteristic shape of a split signal is called multiplicity and provides additional information about the molecule. This multiplicity can be calculated using the N+1 rule. This rule states that if a proton shows scalar coupling with N protons attached to contiguous carbon nuclei, its signal will split into N+1 peaks with relative intensities defined by the Pascal’s triangle (Figure 6). Peak splitting because of the scalar coupling causes a reduction of the peak intensity. Finally, the observation of signals arising from an effect called the nuclear Overhauser effect (NOE) is essential for structural determination of macromolecules, since it emerges from the interaction of nuclear spins of atoms that are spatially close, but distant in the molecular sequence.6,7,8,9,10
Figure 6: Example of a scalar coupling. If there is no scalar coupling (top), NMR signals from HA and HB appear as simple peaks. However, if the two nearby protons HA and HB show scalar coupling with a constant J (bottom), the signals will split. Both protons HA and HB are coupled with one proton attached to a contiguous carbon nucleus, following the N+1 rule each proton signal will split into two signals, forming a doublet and the split distance will be equal to the coupling constant, J.
In this context, to interpret an NMR spectrum it is necessary to use all that information to assign each observed signal to the corresponding atomic nucleus of the molecule(s) in the sample. This process is called spectral assignment and it can be difficult to achieve with complex molecules. For this reason, many types of NMR experiments providing different and complementary information are used to characterize a sample.11
Upfield vs downfield NMR
As seen in Figure 5, the same kind of nuclei can generate signals with different chemical shift values. These chemical shifts differ as the magnetic field sensed by a particular nucleus strongly depends on its local chemical environment. The circulation of electrons in the surroundings of a nucleus creates small magnetic fields that oppose the applied external field. This “shielding” effect (σ) is directly proportional to the electronic density around the nucleus. As a result, the effective magnetic field acting on the nucleus is lower and the Larmor frequency is affected (Eq. 4). When there is a high electronic density around the considered nucleus, the shielding effect is high, the Larmor frequency decreases and so does the chemical shift (it moves upfield). On the contrary, when the electronic density is low in the vicinity of the nucleus, the shielding effect is low, the Larmor frequency takes higher values and so does the chemical shift (it moves downfield).6,7,8,12
Therefore, in NMR spectroscopy, upfield and downfield are terms that refer to the regions of lower and higher values, respectively, within the chemical shift scale (Figure 7).6,7,8,12
Figure 7: 1H NMR chemical shift scale indicating the downfield and upfield regions.
Hydrogen nuclei from methyl groups or aliphatic molecules are strongly shielded and their typical chemical shift values are located upfield. On the other hand, hydrogen nuclei attached to electronegative atoms (such as oxygen or nitrogen) or close to electronegative groups (such as carboxylic acids or aldehydes) are deshielded and show chemical values located downfield. This illustrated and discussed further in a later section, NMR charts.
Proton NMR vs carbon NMR
The principal constituent elements of organic and biological molecules are hydrogen and carbon. As described above, NMR spectroscopy can only be applied on NMR-active nuclei (that is, nuclei with I ≠ 0). In the case of hydrogen, the most abundant isotope is NMR-active (1H, 99.98%, I = ½). In the case of carbon, its most abundant isotope is not NMR-active (12C, 98.89%, I = 0). NMR spectrometers can only detect the isotope 13C, which has an abundance of 1.11%. Moreover, the magnetogyric ratio of 13C is also lower by a factor of four than that of 1H (see Table 1). Both factors make 13C-NMR significantly less sensitive than 1H-NMR (see Table 1). This difference in sensitivity leads to longer experimental times in the case of 13C (hours) compared to 1H (seconds or minutes) 13,14
The chemical shift of 1H typically occurs in the range 0 to 14 ppm, whereas, the 13C chemical shifts occur over much a larger range, typically 10 to 220 ppm. This dependence of the chemical shift values on the type of nuclei arise from the fact that different nuclei possess different Larmor frequencies (as they depend on the magnetogyric ratio, as mentioned before). These increased shifts in 13C-NMR results in a better resolution compared to 1H-NMR, as the signals are normally more dispersed.
Additionally, scalar coupling between 13C is rarely observed because, due to its low natural occurrence, two 13C atoms are unlikely to be found close enough to establish interactions between their nuclear spins. However, the coupling of 13C atoms with other nuclei is possible and it can further reduce the sensitivity of the technique. The reason for this is that 13C coupling constants are large and the reduction of signal intensity upon splitting (see section 3) is more marked when coupling constants are large. For this reason, 13C-NMR experiments are usually performed using special pulse sequences capable of removing the scalar coupling between 13C and 1H.14
There are a number of ways in which the sensitivity of 13C-NMR can be improved, these include:
- 13C-enrichment of the sample
- Increasing the number of accumulated spectra, therefore reducing the signal-to-noise ratio
- Using NMR pulses to increase the population difference between nuclear spin energy levels14
Despite the limitations of 13C-NMR, it offers valuable information that is not accessible using only 1H-NMR. The identification of primary, secondary, tertiary and quaternary carbons for example. For this reason, 13C-NMR and 1H-NMR are often used jointly in NMR laboratories as a basic approach for molecular structure determination.14
Table 1: Comparison of 1H and 13C NMR properties.15
Natural abundance (%)
Nuclear spin quantic number, I
Magnetogyric ratio (rad·T-1·s-1)
Relative sensitivity a
Larmor frequency (MHz)b
Chemical shift range (ppm)
0 – 14
10 – 220
a Considering a constant magnetic field and the same number of nuclei.
b Considering a magnetic field with a flux density of 14.0954 T.
By convention, the chemical shift scale in an NMR spectrum is represented from right to left. As described above, the zero value is established using a standard compound whose carbon and hydrogen atoms are strongly shielded and hence, their signals appear in the furthest upfield region (as seen in Figure 7). The assignment of the NMR spectra is usually performed with the help of NMR charts or diagrams that facilitate the identification of the NMR signals.
Hydrogens or carbons that are highly shielded, such as the ones of methyl groups, have low chemical shift values. However, hydrogens attached to very electronegative groups (e.g., carboxylic acids, ketones or aldehydes) have high chemical shift values (Figures 8 and 9).
These charts represent typical chemical shifts, but sometimes the values could be displaced to other regions of the scale.16 For instance, in large macromolecules, a distant chemical group can be relocated due to spatial rearrangements of the tridimensional structure. This relocation could alter the chemical environment of the measured nucleus, leading to a change in its chemical shift value.
In order to facilitate NMR spectra assignment, there are public NMR libraries or databases (such as the Biological Magnetic Resonance Data Bank or the Spectral Database for Organic Compounds) containing NMR spectra and chemical shift values for thousands of biochemical molecules and chemical compounds.
Figure 8: 1H-NMR chart showing the typical chemical shift values for different types of hydrogen atoms.
The magnetic pulses employed in NMR have been extensively developed over time such that there is now a myriad of diverse NMR experiments optimized to obtain a large amount of information about the sample. Two of the most common NMR variants are 2D NMR and solid-state NMR.
a. 2D NMR
Macromolecules, such as proteins, have a large number of NMR-active nuclei and, consequently, their NMR spectra are complex with many overlapping peaks. In addition, relaxation is faster in large molecules, which causes peak broadening and loss of resolution. To address these limitations, 2D NMR experiments generate spectra defined by two chemical shift axes (instead of one, as in 1D spectra), with signals that correlate pairs of different nuclei. Three examples of 2D NMR experiments are COSY, TOCSY and NOESY.6,7,8,9
- COSY (COrrelated SpectroscopY) spectra display peaks that correlate pairs of nuclei that are separated by a maximum of three chemical bonds. This correlation arises from the interaction between nuclear spins through scalar coupling (Figure 10).
- TOCSY (TOtal Correlated SpectroscopY) spectra show signals correlating pairs of nuclei that are part of the same spin system (a spin system is a set of nuclei whose spins interact with one another, that is they are coupled) (Figure 10).
- NOESY (Nuclear Overhauser Effect SpectroscopY) experiments are very important in the structural elucidation of macromolecules because they provide information about their spatial organization. NOESY spectra contain peaks that correlate pairs of nearby nuclei (typically, separated by less than 5-6 Å). Differently to COSY, NOESY correlation arises from the nuclear Overhauser effect, in which interaction occurs when two nuclei are spatially close, no matter the number of chemical bonds separating them. 6,7,8,9
Figure 10: Examples of 1H,1H COSY and 1H,1H TOCSY spectra for a molecule with the structure A-B-C-D and hydrogen atoms attached to each of them. The COSY spectrum only shows the peaks arising from the correlation between two hydrogens separated by a maximum of three chemical bonds (this is H-A-B-H; H-B-C-H; and H-C-D-H). The TOCSY spectrum shows the peaks arising from the correlation between two hydrogens belonging to the same spin system (in this case, all the possible H-H correlations).
b. Solid-state NMR
In spite of the fact that most NMR analyses are carried out on samples in solution, the field of solid-state NMR has developed significantly in the last decade. Solid-state NMR is one of the most powerful techniques for the study of molecular structures and dynamics in solid samples. This NMR variant has special features and requires different experimental designs.17
Solution NMR and solid-state NMR show remarkable differences, mainly due to the fact that molecules in solution are able to move freely and nuclear spin interactions are averaged. However, in solid samples there is little or no molecular motion and, as a result, nuclear spin interactions depend on the spatial direction (this is termed anisotropic interactions). This anisotropy causes the broadening of the NMR spectral signals (Figure 11, bottom spectrum). To address this issue, scientists using solid-state NMR have developed special techniques that prevent the loss of sensitivity and resolution.17
The most well-known solid state NMR technique is magic angle spinning (MAS). The approach used in this technique involves placing the sample inside a rotor which is spun at high speed, forming a particular angle (magic angle ≈ 54.74º) with respect to the direction of the external magnetic field. The effect of this rotation is the cancelation of all the anisotropic spin interactions (including dipolar, chemical shift anisotropy and quadrupolar interactions) (Figure 11).17
Strengths and weaknesses of NMR and common problems
NMR spectroscopy is a powerful technique that has many advantages over other techniques, but it has some limitations. These are summarized in Table 2:18
Table 2: Summary of the principal strengths and weaknesses of NMR spectroscopy.
Amenable to many sample types: solutions, solids, tissues, gas
Only nuclei with I ≠ 0 can be measured
Provides a range of information: molecular structure, dynamics, interactions, physical parameters, quantification
Molecules can be measured in their native state
Expensive equipment and maintenance
Easy compound identification using NMR libraries
Some experiments are time-consuming
A high level of automation is possible
Magnetic field inhomogeneities must be corrected
Instrumental optimization required prior to measurements (tuning, matching, shimming)
Spectral assignment and data analysis can be complex in some kinds of samples
Easy and inexpensive sample preparation
Spectral interferences from impurities and solvents
Many quick and easy experiments
One of the most common problems encountered in NMR spectroscopy, as mentioned in Table 2, is the presence of interfering substances, such as traces of impurities or solvents, that give rise to the appearance of non-desired peaks in the spectrum.
The analytes contained in NMR samples are usually obtained by a synthesis and/or purification process in which many substances are involved. For this reason, it is not infrequent to find that certain amounts of those substances remain in the final sample as impurities. Occasionally, the analyte undergoes transformations or degradation, which can lead to the appearance of undesirable chemical species in the sample. If these impurities have NMR-active nuclei, they can hamper the correct assignment of the NMR spectrum. Generally, NMR impurities are found in trace concentration and therefore they are relatively easy to identify, as their NMR peaks show very low intensities compared to those of the analyte. To make it easier to characterize impurities, laboratories often make use of tables that summarize the chemical shifts of the most common impurities.19,20,21
NMR solvent peaks
Solvents used in NMR spectroscopy usually contain NMR-active nuclei, especially 1H, and hence, they can potentially cause interferences in the NMR spectra. Unlike trace impurities, the solvent is present in the sample at a very high concentration and peaks arising from it are usually huge. To avoid this problem, it is very important to know exactly the chemical shift of the solvent peaks to control to what extent they can be concealing any analyte signal. On the other hand, the customary strategy to reduce the effect of hydrogen-containing solvent peaks is to use deuterated solvents (some deuterated solvent must always be present in the sample as the lock system of NMR spectrometers uses the 2H signal to monitor the homogeneity of the magnetic field). These solvents have their 1H nuclei substituted by 2H, thus considerably reducing the intensity of the solvent peaks. However, in spite of the fact that the usual percentage of deuteration is close to 100%, due to the high solvent concentration, their peaks can still be too intense and hinder the correct visualization of the analyte signals. For this reason, there are some NMR pulses available that are able to reduce the solvent peak perturbations in NMR spectra, especially for aqueous samples (for instance, pulses with presaturation or gradient-suppression pulses).22,23,24
Applications of NMR
NMR spectroscopy is widely applied across many fields and is especially common in the fields of chemistry and the life sciences.
NMR applications in chemistry
In chemistry, the main application of NMR spectroscopy is the identification and structural elucidation of organic, organometallic and biochemical molecules. Generally, the identification of compounds is complemented with data obtained with other techniques, such as mass spectrometry, infrared spectroscopy and elemental analysis. Moreover, the proportionality between the area of the signals and the amount of nuclei that generate it allows NMR spectroscopy to be used as a quantitative analysis tool.15 Some examples of NMR applications in chemistry-related fields are:
- Chemistry: structural determination of new compounds, quality control of products and purity determination25
- Pharmaceutics: study of structure, dynamics and molecular interactions for drug discovery, quality control and purity determination of drugs 26
- Petrochemistry: analysis of rock materials to check the suitability of an oil reservoir to be exploited, solid state NMR composition analysis of petroleum derivatives, quality control of products27
- Materials: characterization of new materials by solids state NMR 28
NMR applications in the life sciences
Within the life sciences, NMR spectroscopy has been widely applied to the structural resolution of biological macromolecules, including peptides, proteins, lipids, carbohydrates and nucleic acids. These systems are highly complex, and it is therefore necessary to employ a special approach. This includes:
- Isotopic labeling to enrich the sample in 13C and 15N, or even in 2H
- The use of special NMR pulses to reduce signal overlapping and gain resolution
- Employing NMR experiments of high dimensionality (2D, 3D or even higher)
Once the NMR assignment is achieved, the data obtained are processed to obtain information about chemical shifts, torsion angles and distance restraints between atoms. This information is then used to calculate the molecular structure using a methodology that employs computer software developed for that purpose. The software generates molecular structures that fulfill the imposed restraints, minimizing their energy (since the lowest energy structures are the most stable and thus, the most probable).29,30
Alongside the structural elucidation, NMR spectroscopy can also be used to extract information about molecular dynamics such as relaxation times, structural rigidity and chemical exchange as well as interactions between molecules (chemical shift perturbations, intermolecular magnetization transfer).31,32 In this context, solid state NMR is useful to study proteins interacting with lipid structures or other biological systems that behave like a condensed phase.33
Some examples of NMR applications in life science-related fields are:
- Molecular biology and biophysics: study of structure, dynamics and molecular interactions of peptides, proteins, nuclei acids, carbohydrates and other biomolecules31,32
- Health sciences: analysis of biological fluids to obtain metabolic profiles related to diseases (metabolomics), use of NMR imaging techniques for medical diagnosis34,35
- Food science: NMR fingerprint analysis to check quality or authenticity of food samples36, wine and cannabis.
COSY Correlated spectroscopy
DSS Sodium trimethylsilylpropanesulfonate
FID Free induction decay
MAS Magic-angle spinning
NMR Nuclear magnetic resonance
NOE Nuclear Overhauser effect
NOESY Nuclear Overhauser effect spectroscopy
TOCSY Totally correlated spectroscopy
1. Rabi II, Millman S, Kusch P, and Zacharias JR. The molecular beam resonance method for measuring nuclear magnetic moments. the magnetic moments of 3Li6, 3Li7 and 9F19. Phys Rev. 1939. 55(6): 526. doi: 10.1103/PhysRev.55.526
2. Bloch F, Hansen W, and Packard M. Nuclear induction. Phys Rev. 69: 127L. doi: 10.1103/PhysRev.70.460
3. Purcell EM, Torrey HC, and Pound RV. Resonance absorption by nuclear magnetic moments in a solid. 1946. Phys Rev. 69: 37L. doi: 10.1103/PhysRev.69.37
4. Emsley JW, and Feeney J. Milestones in the first fifty years of NMR. 1995. Progr Nucl Mag Res Sp. 28(1): 1-9. doi: 10.1016/0079-6565(95)01023-8
5. Marion D. An introduction to biological NMR spectroscopy. Mol Cell Proteomics. 2013. 12(11): 3006-3025. doi: 10.1074/mcp.O113.030239
6. Friebolin H & Becconsall JK. (2005). Basic one-and two-dimensional NMR spectroscopy (Vol. 7). Weinheim: Wiley-vch. 2005.
7. Hore PJ. Nuclear magnetic resonance. USA: Oxford University Press. 2015.
8. Derome AE. Modern NMR techniques for chemistry research. Elsevier. 2013.
9. Jacobsen NE. NMR data interpretation explained: understanding 1D and 2D NMR spectra of organic compounds and natural products. John Wiley & Sons. 2016.
10. Bible RH. Interpretation of NMR spectra: an empirical approach. Springer Science & Business Media. 2013.
11. Wüthrich K. Protein structure determination in solution by NMR spectroscopy. 1990. J Biol Chem. 1990. 265(36): 22059-22062. doi: 10.1016/S0021-9258(18)45665-7
12. Xu S. 1D and 2D NMR experiment methods. 2011. Available online. Accessed on 28/09/2021.
13. Silverstein RM. Spectrometric identification of organic compounds. New York: Wiley. 1991.
14. Balci M. Basic 1H-and 13C-NMR spectroscopy. Elsevier. 2005.
15. Skoog DA, Holler FJ, and Crouch SR. Principles of instrumental analysis. Cengage learning, 2017.
16. Du Vernet R & Boekelheide V. Nuclear magnetic resonance spectroscopy. ring-current effects on carbon-13 chemical shifts. P Natl Acad Sci USA. 1974. 71(8): 2961-2964. doi: 10.1073/pnas.71.8.2961
17. Brown SP & Emsley L. Solid-state NMR. In: Vo-Dinh, T. (Ed.). Handbook of spectroscopy. John Wiley & Sons. 2006.
18. Emwas AHM. The strengths and weaknesses of NMR spectroscopy and mass spectrometry with particular focus on metabolomics research. In Metabonomics (pp. 161-193). Humana Press, New York, NY. 2015. doi: 10.1007/978-1-4939-2377-9_13
19. Fulmer GR, Miller AJ, Sherden NH et al. NMR chemical shifts of trace impurities: common laboratory solvents, organics, and gases in deuterated solvents relevant to the organometallic chemist. Organometallics. 2010. 29(9): 2176-2179. doi: 10.1021/om100106e
20. Maggio RM, Calvo NL, Vignaduzzo SE, & Kaufman TS. Pharmaceutical impurities and degradation products: Uses and applications of NMR techniques. J Pharmaceut Biomed. 2014. 101: 102-122. doi: 10.1016/j.jpba.2014.04.016
21. Babij NR, McCusker EO, Whiteker GT, et al. NMR chemical shifts of trace impurities: Industrially preferred solvents used in process and green chemistry. Org Process Res Dev. 2016. 20(3): 661-667. doi: 10.1021/acs.oprd.5b00417
22. Guéron M, Plateau P, & Decorps M. Solvent signal suppression in NMR. Prog Nucl Mag Res Sp. 1991. 23(2): 135-209. doi: 10.1016/0079-6565(91)80007-O
23. Simpson AJ, & Brown SA. Purge NMR: effective and easy solvent suppression. J Magn Reson. 2005. 175(2): 340-346. doi: 10.1016/j.jmr.2005.05.008
24. Adams RW, Holroyd CM, Aguilar JA, Nilsson, M, & Morris, GA. “Perfecting” WATERGATE: clean proton NMR spectra from aqueous solution. Chem Commun. 2013. 49(4): 358-360. doi: 10.1039/C2CC37579F
25. Maciel GE. NMR in industrial process control and quality control. In Nuclear Magnetic Resonance in Modern Technology (pp. 225-275). Springer, Dordrecht.
26. Diercks T, Coles M, & Kessler H. Applications of NMR in drug discovery. Curr Opin Chem Biol. 2001. 5(3): 285-291. doi: 10.1016/S1367-5931(00)00204-0
27. Olaide AJ, Olugbenga E & Abimbola D. A review of the application of nuclear magnetic resonance in petroleum industry. Int J Geosci. 2020. 11(04): 145. doi: 10.4236/ijg.2020.114009
28. Brown SP. Applications of high-resolution 1H solid-state NMR. Solid State Nucl Mag. 2012. 41: 1-27. doi: 10.1016/j.ssnmr.2011.11.006
29. Fan TWM, & Lane AN. Applications of NMR spectroscopy to systems biochemistry. Prog Nucl Mag Res Sp. 2016. 92: 18-53. doi: 10.1016/j.pnmrs.2016.01.005
30. Wüthrich K. The way to NMR structures of proteins. Nat Struct Biol. 2001. 8(11): 923-925. doi: 10.1038/nsb1101-923
31. Ishima R, & Torchia DA. Protein dynamics from NMR. Nat Struct Biol. 2000. 7(9): 740-743. doi: 10.1038/78963
32. Takeuchi K, & Wagner G. NMR studies of protein interactions. Curr Opin Struct Biol. 2006. 16(1): 109-117. doi: 10.1016/j.sbi.2006.01.006
33. Ladizhansky V. Applications of solid-state NMR to membrane proteins. BBA-Proteins Proteom. 2017. 1865(11): 1577-1586. doi: 10.1016/j.bbapap.2017.07.004
34. Markley JL, Brüschweiler R, Edison AS et al. The future of NMR-based metabolomics. Curr Opin Biotech. 2017. 43: 34-40. doi: 10.1016/j.copbio.2016.08.001
35. Vlaardingerbroek MT & Boer JA. Magnetic resonance imaging: theory and practice. 2013. Springer Science & Business Media.
36. Hatzakis E. Nuclear magnetic resonance (NMR) spectroscopy in food science: A comprehensive review. Compr Rev Food Sci F. (2019). 18(1): 189-220. doi: 10.1111/1541-4337.12408