Solid-state nuclear magnetic resonance chemical shifts

A solution-state and solid-state nuclear magnetic resonance study of the complex and its separate components in both their neutral and ionized (TMP hydrochloride and SMZ sodium salt) forms was undertaken in order to elucidate the TMP-SMZ interactions. Inspection of the data for the complex in the solid state shows that the 13C chemical shifts are consistent with the ionic structure proposed by Nakai and coworkers105 (14). Stabilization of the complex is achieved by the resulting ionic interaction and by the formation of two intermolecular hydrogen bonds. 

Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a powerful technique used in the analysis of solids, and is currently finding more and more applications, particularly in the analysis of pharmaceutical formulations. It is a non-destructive, non-invasive technique that can be employed to simultaneously examine the physical and chemical states of both the active pharmaceutical ingredient (API) and the excipients present as they exist within the formulation. It is also highly selective, as nuclei of the API often have different chemical shifts than do common excipients. 

Abstract Modern solid state nuclear magnetic resonance presents new powerful opportunities for the elucidation of medium range order in glasses in the sub-nanometer region. In contrast to standard chemical shift spectroscopy, the strategy presented here is based on the precise measurement and quantitative analysis of internuclear magnetic dipole-dipole interactions, which can be related to distance information in a straightforward manner. The... 

Solid-state nuclear magnetic resonance (NMR) is nowadays an established technique in the pharmaceutical industry, used mainly as a tool to distinguish different polymorphs. Its advantages are high versatility and resolution, which allow for studies of aU the materials in a formulation. Compared to, for example, powder XRPD and Raman scattering, spectral overlap is most often much less of a problem in NMR. Also, the primary parameter, the resonance frequency or the chemical shift, is very sensitive not only to the intramolecular structure but also to intermolecular interactions and spatial arrangement, which is the basis for polymorph selectivity. A range of nuclei can be studied for complementary information, for example, H, N, and T. 

M.A. Eastman, G.A. Barral, A.J. Pines, Variable-angle correlation spectroscopy in solid-state nuclear magnetic resonance, J. Chem. Phys. 97 (1992) 4800-4808. (d) A-C. Kolbert, R.G. Griffin, Two-dimensional resolution of isotropic and anisotropic chemical shifts in magic angle spinning NMR, Chem. Phys. Lett. 166 (1990) 87—91. 

Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a more advanced method for differentiating the polymorphs of a material. The substance is placed in a strong magnetic field and subjected to radiofrequency radiation. The individual nuclei experience different magnetic environments and thus show different changes in resonant frequency characterized by chemical shift. SSNMR spectra show sharp resonance at chemical shifts characteristic of the molecular and crystal structure. The polymorphs are differentiated by their characteristic spectra. 

Figure 9 (A) Typical line shape of an observed quadrupolar nucleus S, showing the second-order quadrupole shift AcTqs, and the relative position of the centre-of-gravity with respect to the isotropic chemical shift ajso- (B) Al solid-state MAS NMR spectrum of Sr8(AI02)i2-Se2 at 78.15 MHz (7.05 T). Asterisks denote sidebands. Reproduced with permission of Elsevier Science Publishers from Weller MT, Brenchley ME, Apperley DC and Davies NA (1994) Correlations between aI magic-angle spinning nuclear magnetic resonance spectra and the coordination geometry of framework alumlnates. Solid State Nuclear Magnetic Resonance Z 103-106.

D. Stueber and D. M. Grant, The C13 chemical shift tensor principal values and orientations in dialkyl carbonates and trithiocarbonates, Solid State Nuclear Magnetic Resonance, vol. 22, no. 4, pp. 439—457, 2002. 

Muller, D., W. Gessner, A. Samoson, E. Lippmaa and G. Scheler. 1986b. Solid-state aluminium-27 nuclear magnetic resonance chemical shift and quadrupole data for condensed A104 tetrahedra./. Chem. Soc. Dalton Trans. 1277-1281. 

In addition to the above prescriptions, many other quantities such as solution phase ionization potentials (IPs) [15], nuclear magnetic resonance (NMR) chemical shifts and IR absorption frequencies [16-18], charge decompositions [19], lowest unoccupied molecular orbital (LUMO) energies [20-23], IPs [24], redox potentials [25], high-performance liquid chromatography (HPLC) [26], solid-state syntheses [27], Ke values [28], isoelectrophilic windows [29], and the harmonic oscillator models of the aromaticity (HOMA) index [30], have been proposed in the literature to understand the electrophilic and nucleophilic characteristics of chemical systems. 

Nuclear magnetic resonance spectra show that the compound exists as a monomer in the molten state IR and Raman data show that the same molecular structure exists for the solid state Sawodny and Goubeau calculated the force constants from the normal vibrations of the molecule, after they had corrected the original assignments of the bands A bond number of 0.78 was found for the P—B bond. The chemical shifts and coupling constants from the H and B n.m.r. spectra for molten BH3PH3 are given in Table 9... 

Physicists have long been aware of the power and usefulness of high-resolution solid-state NMR. Even prior to the development of cross-polarization, in the early to mid-seventies, it was clear that, by recording the nuclear magnetic resonance spectrum when the sample was spun at the magic angle (5 M1) to the magnetic field, chemical shifts could be readily identified... 

Nuclear magnetic resonance spectroscopy of the 27Al nucleus, both in solution and the solid state, has proved useful for the determination of the coordination numbers and, to some extent, the stereochemistry of Al. Four-, 5-, and 6-coordinate geometries can be differentiated on the basis of their chemical shifts. 

The structural distortions of phyllosilicate minerals have been investigated by solid-state Si nuclear magnetic resonance spectroscopy (NMR) [24], In trioctahedral layer silicates such as talc, the wSi chemical-shift value is related to the amount of >VA1 substitution and/or distortion of the tetrahedral sheet structure. 

The ultimate molecular level characterization of a pharmaceutical material is performed on the level of individual chemical environments of each atom in the compound, and this information is best obtained using nuclear magnetic resonance (NMR) spectroscopy. Advances in instrumentation and computer pulse sequences currently allow these studies to be carried out routinely in the solid state.2 Although any nucleus that can be studied in the solution phase also can be studied in the solid state, most work has focused on studies. H-NMR remains an extremely difficult measurement in the solid state, and the data obtained from such work can be obtained only at medium resolution. The main problem is that H-NMR has one of the smallest isotropic chemical shift ranges (12 ppm), but has peak broadening effects that can span several parts per million in magnitude. 

The activation volume, obtained from the pressure dependence of the reaction rate, has become a well-established, and often decisive, criterion for the determination of the reaction mechanism, so that variable-pressure NMR has also become an important tool in the understanding of chemical reactions. High gas pressures can be used to produce increased concentrations of a gas in solution, leading to faster reaction rates, advantageous shifts in chemical equilibria, or even entirely new chemical species. High-pressure NMR is an obvious technique for the study of such reactions. Nuclear magnetic resonance has also proven to be a powerful technique in solid-state physics, where variable-pressure experiments can be used to study phase transitions, transport phenomena, and electronic properties. 

Quantum chemical nuclear magnetic resonance (NMR) chemical shift calculations enjoy great popularity since they facilitate interpretation of the spectroscopic technique that is most widely used in chemistry [1-11], The reason that theory is so useful in this area is that there is no clear relationship between the experimentally measured NMR shifts and the structural parameters of interest. NMR chemical shift calculations can provide the missing connection and in this way have proved to be useful in many areas of chemistry. A large number of examples including the interpretation of NMR spectra of carbocations [12], boranes [10, 13], carboranes [10, 13-15], low-valent aluminum compounds [16-18], fullerenes [19-21] as well as the interpretation of solid-state NMR spectra [22-26] can be found in the literature. 

In a molecule of any kind a particular nuclear spin is surrounded by a large number of electrons and may interact with other nuclear spins in the molecule. The presence of the electrons leads to a shielding of the externally applied magnetic field that is different for the nuclei of atoms in different chemical environments, so that, for example, the frequency in a particular external magnetic field for a atom that is part of a —CH3 group is different from that of a atom in the backbone of a molecule. The difference between the frequency observed for a spin in a particular molecular environment and that which would be observed for the free spin is called the chemical shift. The sensitivity to chemical environment is in fact such that atoms several chemical bonds away can influence the precise frequency of resonance. In the solid state, however, the resonances are broadened by several effects and overlap. 

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