Nuclear magnetic resonance crystallography

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Nuclear magnetic resonance crystallography (NMR crystallography) is a method which utilizes primarily NMR spectroscopy to determine the structure of solid materials on the atomic scale. Thus, solid-state NMR spectroscopy would be used primarily, possibly supplemented by quantum chemistry calculations (e.g. density functional theory), [1] powder diffraction [2] etc. If suitable crystals can be grown, any crystallographic method would generally be preferred to determine the crystal structure comprising in case of organic compounds the molecular structures and molecular packing. The main interest in NMR crystallography is in microcrystalline materials which are amenable to this method but not to X-ray, neutron and electron diffraction. This is largely because interactions of comparably short range are measured in NMR crystallography.

Contents

Introduction

When applied to organic molecules, NMR crystallography aims at including structural information not only of a single molecule but also on the molecular packing (i.e. crystal structure). [3] [4] Contrary to X-ray, single crystals are not necessary with solid-state NMR and structural information can be obtained from high-resolution spectra of disordered solids. [5] E.g. polymorphism is an area of interest for NMR crystallography since this is encountered occasionally (and may often be previously undiscovered) in organic compounds. In this case a change in the molecular structure and/or in the molecular packing can lead to polymorphism, and this can be investigated by NMR crystallography. [6] [7]

Dipolar couplings-based approach

The spin interaction that is usually employed for structural analyses via solid state NMR spectroscopy is the magnetic dipolar interaction. [8] Additional knowledge about other interactions within the studied system like the chemical shift or the electric quadrupole interaction can be helpful as well, and in some cases solely the chemical shift has been employed as e.g. for zeolites. [9] The “dipole coupling”-based approach parallels protein NMR spectroscopy to some extent in that e.g. multiple residual dipolar couplings are measured for proteins in solution, and these couplings are used as constraints in the protein structure calculation.

In NMR crystallography the observed spins in case of organic molecules would often be spin-1/2 nuclei of moderate frequency ( 13
C
 , 15
N
 , 31
P
 , etc.). I.e. 1
H
 is excluded due to its large magnetogyric ratio and high spin concentration leading to a network of strong homonuclear dipolar couplings. There are two solutions with respect to 1H: 1
H
 spin diffusion experiments (see below) and specific labelling with 2
H
 spins (spin = 1). The latter is also popular e.g. in NMR spectroscopic investigations of hydrogen bonds in solution and the solid state. [10] Both intra- and intermolecular structural elements can be investigated e.g. via deuterium REDOR (an established solid state NMR pulse sequence to measure dipolar couplings between deuterons and other spins). [11] This can provide an additional constraint for an NMR crystallographic structural investigation in that it can be used to find and characterize e.g. intermolecular hydrogen bonds.

Dipolar interaction

The above-mentioned dipolar interaction can be measured directly, e.g. between pairs of heteronuclear spins like 13C/15N in many organic compounds. [4] Furthermore, the strength of the dipolar interaction modulates parameters like the longitudinal relaxation time or the spin diffusion rate which therefore can be examined to obtain structural information. E.g. 1H spin diffusion has been measured providing rich structural information. [12]

Chemical shift interaction

The chemical shift interaction can be used in conjunction with the dipolar interaction to determine the orientation of the dipolar interaction frame (principal axes system) with respect to the molecular frame (dipolar chemical shift spectroscopy). For some cases there are rules for the chemical shift interaction tensor orientation as for the 13C spin in ketones due to symmetry arguments (sp2 hybridisation). If the orientation of a dipolar interaction (between the spin of interest and e.g. another heteronucleus) is measured with respect to the chemical shift interaction coordinate system, these two pieces of information (chemical shift tensor/molecular orientation and the dipole tensor/chemical shift tensor orientation) combined give the orientation of the dipole tensor in the molecular frame. [13] However, this method is only suitable for small molecules (or polymers with a small repetition unit like polyglycine) and it provides only selective (and usually intramolecular) structural information.

Crystal Structure Refinements

The dipolar interaction yields the most direct information with respect to structure as it makes it possible to measure the distances between the spins. The sensitivity of this interaction is however lacking and even though dipolar-based NMR crystallography makes the elucidation of structures possible, other methods are necessary to obtain high resolution structures. For these reasons much work was done to include the use other NMR observables such as chemical shift anisotropy, J-coupling and the quadrupolar interaction. These anisotropic interactions are highly sensitive to the 3D local environment making it possible to refine the structures of powdered samples to structures rivaling the quality of single crystal X-ray diffraction. These however rely on adequate methods for predicting these interactions as they do not depend in a straightforward fashion on the structure. [14] [15]

Comparison with diffraction methods

A drawback of NMR crystallography is that the method is typically more time-consuming and more expensive (due to spectrometer costs and isotope labelling) than X-ray crystallography, it often elucidates only part of the structure, and isotope labelling and experiments may have to be tailored to obtain key structural information. Also a given molecular structure may not always be suitable for a pure NMR-based NMR crystallographic approach, but it can still play an important role in a multimodality (NMR+diffraction) study. [16]

Unlike in the case of diffraction methods, it appears that NMR crystallography needs to work on a case-by-case basis. The reason is that different molecular systems will exhibit different spin physics and different observables which can be probed. The method may therefore not find widespread use as different systems will require tailored experimental designs to study them.

Related Research Articles

The nuclear Overhauser effect (NOE) is the transfer of nuclear spin polarization from one population of spin-active nuclei to another via cross-relaxation. A phenomenological definition of the NOE in nuclear magnetic resonance spectroscopy (NMR) is the change in the integrated intensity of one NMR resonance that occurs when another is saturated by irradiation with an RF field. The change in resonance intensity of a nucleus is a consequence of the nucleus being close in space to those directly affected by the RF perturbation.

<span class="mw-page-title-main">Chemical structure</span> Organized way in which molecules are ordered and sorted

A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together and can be represented using structural formulae and by molecular models; complete electronic structure descriptions include specifying the occupation of a molecule's molecular orbitals. Structure determination can be applied to a range of targets from very simple molecules to very complex ones.

<span class="mw-page-title-main">Nuclear magnetic resonance spectroscopy</span> Laboratory technique

Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic field. This re-orientation occurs with absorption of electromagnetic radiation in the radio frequency region from roughly 4 to 900 MHz, which depends on the isotopic nature of the nucleus and increased proportionally to the strength of the external magnetic field. Notably, the resonance frequency of each NMR-active nucleus depends on its chemical environment. As a result, NMR spectra provide information about individual functional groups present in the sample, as well as about connections between nearby nuclei in the same molecule. As the NMR spectra are unique or highly characteristic to individual compounds and functional groups, NMR spectroscopy is one of the most important methods to identify molecular structures, particularly of organic compounds.

<span class="mw-page-title-main">Magic angle spinning</span>

In solid-state NMR spectroscopy, magic-angle spinning (MAS) is a technique routinely used to produce better resolution NMR spectra. MAS NMR consists in spinning the sample at the magic angle θm with respect to the direction of the magnetic field.

<span class="mw-page-title-main">Solid-state nuclear magnetic resonance</span>

Solid-state NMR (ssNMR) spectroscopy is a technique for characterizing atomic level structure in solid materials e.g. powders, single crystals and amorphous samples and tissues using nuclear magnetic resonance (NMR) spectroscopy. The anisotropic part of many spin interactions are present in solid-state NMR, unlike in solution-state NMR where rapid tumbling motion averages out many of the spin interactions. As a result, solid-state NMR spectra are characterised by larger linewidths than in solution state NMR, which can be utilized to give quantitative information on the molecular structure, conformation and dynamics of the material. Solid-state NMR is often combined with magic angle spinning to remove anisotropic interactions and improve the resolution as well as the sensitivity of the technique.

The magic angle is a precisely defined angle, the value of which is approximately 54.7356°. The magic angle is a root of a second-order Legendre polynomial, P2(cos θ) = 0, and so any interaction which depends on this second-order Legendre polynomial vanishes at the magic angle. This property makes the magic angle of particular importance in magic angle spinning solid-state NMR spectroscopy. In magnetic resonance imaging, structures with ordered collagen, such as tendons and ligaments, oriented at the magic angle may appear hyperintense in some sequences; this is called the magic angle artifact or effect.

Nuclear magnetic resonance spectroscopy of proteins is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and their complexes. The field was pioneered by Richard R. Ernst and Kurt Wüthrich at the ETH, and by Ad Bax, Marius Clore, Angela Gronenborn at the NIH, and Gerhard Wagner at Harvard University, among others. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.

<span class="mw-page-title-main">Pake doublet</span>

A Pake Doublet is a characteristic line shape seen in solid-state nuclear magnetic resonance and electron paramagnetic resonance spectroscopy. It was first described by George Pake.

In nuclear chemistry and nuclear physics, J-couplings are mediated through chemical bonds connecting two spins. It is an indirect interaction between two nuclear spins that arises from hyperfine interactions between the nuclei and local electrons. In NMR spectroscopy, J-coupling contains information about relative bond distances and angles. Most importantly, J-coupling provides information on the connectivity of chemical bonds. It is responsible for the often complex splitting of resonance lines in the NMR spectra of fairly simple molecules.

<span class="mw-page-title-main">Residual dipolar coupling</span>

The residual dipolar coupling between two spins in a molecule occurs if the molecules in solution exhibit a partial alignment leading to an incomplete averaging of spatially anisotropic dipolar couplings.

<span class="mw-page-title-main">Dihydrogen complex</span> Containing intact H2 as a ligand

Dihydrogen complexes are coordination complexes containing intact H2 as a ligand. They are a subset of sigma complexes. The prototypical complex is W(CO)3(PCy3)2(H2). This class of compounds represent intermediates in metal-catalyzed reactions involving hydrogen. Hundreds of dihydrogen complexes have been reported. Most examples are cationic transition metals complexes with octahedral geometry.

Herbert Sander Gutowsky was an American chemist who was a professor of chemistry at the University of Illinois Urbana-Champaign. Gutowsky was the first to apply nuclear magnetic resonance (NMR) methods to the field of chemistry. He used nuclear magnetic resonance spectroscopy to determine the structure of molecules. His pioneering work developed experimental control of NMR as a scientific instrument, connected experimental observations with theoretical models, and made NMR one of the most effective analytical tools for analysis of molecular structure and dynamics in liquids, solids, and gases, used in chemical and medical research, His work was relevant to the solving of problems in chemistry, biochemistry, and materials science, and has influenced many of the subfields of more recent NMR spectroscopy.

A crystallographic database is a database specifically designed to store information about the structure of molecules and crystals. Crystals are solids having, in all three dimensions of space, a regularly repeating arrangement of atoms, ions, or molecules. They are characterized by symmetry, morphology, and directionally dependent physical properties. A crystal structure describes the arrangement of atoms, ions, or molecules in a crystal.

<span class="mw-page-title-main">Phosphorus-31 nuclear magnetic resonance</span> Spectroscopy technique for molecules containing phosphorus

Phosphorus-31 NMR spectroscopy is an analytical chemistry technique that uses nuclear magnetic resonance (NMR) to study chemical compounds that contain phosphorus. Phosphorus is commonly found in organic compounds and coordination complexes, making it useful to measure 31- NMR spectra routinely. Solution 31P-NMR is one of the more routine NMR techniques because 31P has an isotopic abundance of 100% and a relatively high gyromagnetic ratio. The 31P nucleus also has a spin of 1/2, making spectra relatively easy to interpret. The only other highly sensitive NMR-active nuclei spin 1/2 that are monoisotopic are 1H and 19F.

<span class="mw-page-title-main">Nuclear magnetic resonance</span> Spectroscopic technique based on change of nuclear spin state

Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field and respond by producing an electromagnetic signal with a frequency characteristic of the magnetic field at the nucleus. This process occurs near resonance, when the oscillation frequency matches the intrinsic frequency of the nuclei, which depends on the strength of the static magnetic field, the chemical environment, and the magnetic properties of the isotope involved; in practical applications with static magnetic fields up to ca. 20 tesla, the frequency is similar to VHF and UHF television broadcasts (60–1000 MHz). NMR results from specific magnetic properties of certain atomic nuclei. Nuclear magnetic resonance spectroscopy is widely used to determine the structure of organic molecules in solution and study molecular physics and crystals as well as non-crystalline materials. NMR is also routinely used in advanced medical imaging techniques, such as in magnetic resonance imaging (MRI). The original application of NMR to condensed matter physics is nowadays mostly devoted to strongly correlated electron systems. It reveals large many-body couplings by fast broadband detection and it should not to be confused with solid state NMR, which aims at removing the effect of the same couplings by Magic Angle Spinning techniques.

Nucleic acid NMR is the use of nuclear magnetic resonance spectroscopy to obtain information about the structure and dynamics of nucleic acid molecules, such as DNA or RNA. It is useful for molecules of up to 100 nucleotides, and as of 2003, nearly half of all known RNA structures had been determined by NMR spectroscopy.

<span class="mw-page-title-main">Paramagnetic nuclear magnetic resonance spectroscopy</span> Spectroscopy of paramagnetic compounds via NMR

Paramagnetic nuclear magnetic resonance spectroscopy refers to nuclear magnetic resonance (NMR) spectroscopy of paramagnetic compounds. Although most NMR measurements are conducted on diamagnetic compounds, paramagnetic samples are also amenable to analysis and give rise to special effects indicated by a wide chemical shift range and broadened signals. Paramagnetism diminishes the resolution of an NMR spectrum to the extent that coupling is rarely resolved. Nonetheless spectra of paramagnetic compounds provide insight into the bonding and structure of the sample. For example, the broadening of signals is compensated in part by the wide chemical shift range (often 200 ppm in 1H NMR). Since paramagnetism leads to shorter relaxation times (T1), the rate of spectral acquisition can be high.

<span class="mw-page-title-main">Lyndon Emsley</span> British chemist

David Lyndon Emsley FRSC is a British chemist specialising in solid-state nuclear magnetic resonance and a professor at EPFL. He was awarded the 2012 Grand Prix Charles-Leopold Mayer of the French Académie des Sciences and the 2015 Bourke Award of the Royal Society of Chemistry.

<span class="mw-page-title-main">Svyatoslav Gabuda</span> Russian physicist

Svyatoslav Petrovich Gabuda was a Soviet/Russian physicist, professor, and doctor of physical and mathematical sciences.

Structural chemistry is a part of chemistry and deals with spatial structures of molecules and solids. For structure elucidation a range of different methods is used. One has to distinguish between methods that elucidate solely the connectivity between atoms (constitution) and such that provide precise three dimensional information such as atom coordinates, bond lengths and angles and torsional angles.

References

  1. ↑ Robinson, Philip (26 February 2009). "Crystal clear method for identifying powders". Highlights in Chemical Technology. Retrieved 2015-10-22.
  2. ↑ Harris KDM, Xu M (2009). Combined Analysis of NMR & Powder Diffraction Data. Wiley-Blackwell. ISBN   978-0-470-69961-4.
  3. ↑ Taulelle F (2004). "NMR crystallography: crystallochemical formula and space group selection". Solid State Sciences. 6 (10): 1053–1057. Bibcode:2004SSSci...6.1053T. doi:10.1016/j.solidstatesciences.2004.07.033.
  4. 1 2 Macholl S; Börner F; Buntkowsky G (2004). "Revealing the configuration and crystal packing of organic compounds by solid-state NMR spectroscopy: methoxycarbonylurea, a case study". Chemistry. 10 (19): 4808–4816. doi:10.1002/chem.200400191. PMID   15372663.
  5. ↑ Sakellariou, Dimitris; Brown, Steven P.; Lesage, Anne; Hediger, Sabine; Bardet, Michel; Meriles, Carlos A.; Pines, Alexander; Emsley, Lyndon (2003). "High Resolution NMR Correlation Spectra of Disordered Solids". J. Am. Chem. Soc. 125 (14): 4376–4380. doi:10.1021/ja0292389. PMID   12670262.
  6. ↑ Harris RK (2006). "NMR studies of organic polymorphs & solvates". Analyst. 131 (3): 351–373. Bibcode:2006Ana...131..351H. doi:10.1039/b516057j. PMID   16496044.
  7. ↑ Reutzel-Edens SM (2008). "NMR Crystallography and the Elucidation of Structure-Property Relationships in Crystalline Solids". Engineering of Crystalline Materials Properties. NATO Science for Peace and Security Series B: Physics and Biophysics. pp. 351–374. doi:10.1007/978-1-4020-6823-2_17. ISBN   978-1-4020-6822-5.{{cite book}}: |journal= ignored (help)
  8. ↑ Schmidt-Rohr K.; Spiess H.W. (1994). Multidimensional Solid-State NMR and Polymers. Academic Press. ISBN   978-0-12-626630-6.
  9. ↑ Brouwer DH (2008). "NMR Crystallography of Zeolites: Refinement of an NMR-Solved Crystal Structure Using ab Initio Calculations of 29Si Chemical Shift Tensors". J. Am. Chem. Soc. 130 (20): 6306–6307. doi:10.1021/ja800227f. PMID   18433131.
  10. ↑ Kohen A.; Limbach H.-H. (2005). Isotope Effects In Chemistry and Biology. Boca Raton, FL: CRC Press. ISBN   978-0-8247-2449-8.
  11. ↑ Sack I; Goldbourt A; Vega S; Buntkowsky G (1999). "Deuterium REDOR: principles and applications for distance measurements". J Magn Reson. 138 (1): 54–65. Bibcode:1999JMagR.138...54S. doi:10.1006/jmre.1999.1710. PMID   10329226.
  12. ↑ Elena, Bénédicte; Pintacuda, Guido; Mifsud, Nicolas; Emsley, Lyndon (2006). "Molecular Structure Determination in Powders by NMR Crystallography from Proton Spin Diffusion". J. Am. Chem. Soc. 128 (29): 9555–9560. doi:10.1021/ja062353p. PMID   16848494.
  13. ↑ Mehring M. (1983). High Resolution NMR Spectroscopy in Solids. Berlin, Heidelberg, New York: Springer. ISBN   978-0-387-07704-8.
  14. ↑ Brouwer, DH; Enright, GD (2008). "Probing Local Structure in Zeolite Frameworks: Ultrahigh-Field NMR Measurements and Accurate First-Principles Calculations of Zeolite 29Si Magnetic Shielding Tensors". J. Am. Chem. Soc. 130 (10): 3095–3105. doi:10.1021/ja077430a. PMID   18281985.
  15. ↑ Wylie, BJ; Schwieters, CD; Oldfield, E; Rienstra, CM (2009). "Protein Structure Refinement Using 13Cα Chemical Shift Tensors". J. Am. Chem. Soc. 131 (3): 985–992. doi:10.1021/ja804041p. PMC   2751586 . PMID   19123862.
  16. ↑ Macholl S; Lentz D; Börner F; Buntkowsky G (2007). "Polymorphism of N,N-diacetylbiuret studied by solid-state 13C and 15N NMR spectroscopy, DFT calculations, and X-ray diffraction". Chemistry. 13 (21): 6139–6149. doi:10.1002/chem.200601843. PMID   17480047.
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