SSNMR methods

As mentioned above, the alkali metal chlorides have cubic symmetry about the chlorine nucleus which requires that the EFG to be essentially zero in a perfect crystal. This results in CT NMR spectra with narrow lines that are free of quad-rupolar effects. As the environment aroimd the chlorine nucleus is transformed to lower symmetry, second-order quadrupolar effects begin to be observed, leading to broadened CT lines with quadrupolar line shapes. The broadening of the signals in chlorine CT NMR spectra as the quadrupolar effects become more significant is the most serious limitation to the types of materials which can be studied with typical SSNMR methods. 

Recent developments in bromine and iodine NMR spectroscopy in the last decade are scarce. Based upon our review of the literature, it is clear that Br and I SSNMR applications lie predominantly in systems where the nucleus finds itself in an ionic and highly symmetric (i.e. tetrahedral or octahedral) environment. The recent success of high-field pulsed SSNMR methods in... 

SSNMR methods have been used to investigate several molecular cocrystals and complexes, even in the presence of impurities. A protocol for the application of methods based on dipolar connectivity, CS information, and relaxation measurements using several cocrystals was presented [54]. A plethora of NMR techniques were explored in order to study H-bonding and other intermolecular contacts. In addition, chemical shielding calculations were performed to assign H and C resonances. 

Other reports show that SSNMR methods were explored to prove cocrystal formation of the solids produced during solid form screening activities [54]. H ICS and H correlation experiments were found to be the fastest and most definite methods to prove molecular association. The authors first recommend screening solids by C and H spectra to assess phase purity, confirm the presence of new crystalline species, and identify strong H-bonding between conformers from the downfield H ICS. H- C CP-HETCOR and H- H DQ recoupling experiments can then provide dipolar connectivity to demonstrate molecular association between components. CST calculations can further confirm molecular association. This protocol was vetted with nine cocrystal systems to prove complexation. 

Hu et al. examined the dynamical heterogeneity in a series of 4,4 -dicy-clohejtylmethane diisocyanate-diethyltoluenediamine-poly(tetramethylene oxide) based poly(urethane urea) (PUU) elastomers by ssNMR methods. This included H wideline, Ti and time-domain-WISE experiment, which showed the different mobilities within the polymer. ... 

Tensor correlation methods refer to the selection of two anisotropic interactions so that the pattern of the 2D correlation spectrum can reveal the magnitudes and relative orientation of the two tensorial interactions. Below we will discuss many different SSNMR techniques suggested for the determination of peptide backbone... 

For appropriate comprehension of morphology and the concomitant structure-property correlations in nanocomposites, knowledge of the state and extent of nanofiller dispersion in the matrix is of paramount importance. Numerous methods have been reported in the literature in this regard, for instance, WAXD [6, 38], SAXS [8, 39], SANS [40], SEM, [6, 41], AFM [7, 42], HRTEM, STEM, EELS [43], SSNMR [44], EPRS [45], UV/vis/NIR, FTIR [46], Raman spectroscopy... 

In terms of the structural features that are probed with various analytical methods, solid state nuclear magnetic resonance (SSNMR) may be looked upon as representing a middle ground between IR spectroscopy and X-ray powder diffraction methods. The former provides a measure of essentially molecular parameters, mainly the strengths of bonds as represented by characteristic frequencies, while the latter reflect the periodic nature of the structure of the solid. For polymorphs differences in molecular environment and/or molecular conformation may be reflected in changes in the IR spectrum. The differences in crystal structure that define a polymorphic system are clearly reflected in changes in the X-ray powder diffraction. Details on changes in molecular conformation or in molecular environment can only be determined from full crystal structure analyses as discussed in Section 4.4. 

To understand the function of membrane-active peptides, it is important to know the structure and orientation of the peptide in the membrane. As is evident from Figure 18.1, it is possible to distinguish between, for example, carpet and pore mechanisms of action by determining the peptide s orientation in the membrane. Various techniques, such as electron spin resonance (ESR) [35], infrared (IR) spectroscopy [36-38], circular dichroism (CD) [35, 39,40], and solid-state NMR (SSNMR) [4-7] are used to investigate membrane-active peptides in a quasi-native lipid bilayer environment. In the following sections, methods to determine peptide structure and orientation are presented. 

Most modem SSNMR experiments on the quadmpolar halogen nuclei are carried out on powdered samples. We present briefly here an overview of the most commonly applicable methods to be used on stationary and MAS powdered samples. 

A uniformly labeling scheme is the simplest and most cost-effective biosynthetic labeling method for protein SSNMR. Normally, uniformly C-labeled glucose or glycerol, and N-labeled ammonium chloride or ammonium sulfate are used as the labeled precursors in the growth medium. With a single sample, all the structural constraints can be obtained through a set of correlation experiments and the protein structure can be calculated thereby. This approach has been first demonstrated on microcrystalline proteins of known structure [108-111], and then successfully applied to membrane protein for structure determination [7, 38, 41, 105, 112-114]. 

MAS NOESY experiments have been widely used in SSNMR to study peptide-lipid interactions because of the fast axially rotation and segmental motion of membrane lipids in the liquid crystalline phase which average out efficiently the H- H dipolar couplings, resulting in a high resolution spectrum of membrane lipids under the slow MAS frequencies [166], which leads to the rapid applications of the NOESY-type [167] of solution NMR methods to study peptide-membrane interactions in MAS SSNMR [168-170]. 

Solid-state nuclear magnetic resonance (ssNMR) spectroscopy has emerged over the years as a powerful analytical method in solid-state chemistry, especially with the advancements in techniques that allow the acquisition of high-resolution spectra [47]. In the broadest sense, ssNMR is mostly applied in characterization of crystalline materials as a means to support PXRD structural analyses by providing information on the number of molecules in the asymmetric unit or the symmetry of the occupied positions within the unit cell. Another major field of application is the structural characterization of amorphous and disordered solids where standard X-ray diffraction-based techniques fail to give detailed structural information. When discussing ssNMR in the context of API polymorphism and synthesis of co-crystals,... 

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