Solid-state analysis spectroscopy

The problems involved in quantitative analysis using NMR spectroscopy, have been discussed by several authors and it is evident that it still causes a lot of problems as especially pointed out by Hays55 in his excellent review on the subject. Thus in liquid state NMR spectroscopy the quantitative estimation of atoms and groups involves the use of normal analytical method. In the case of solid state NMR spectroscopy, however, the application of the cross-polarization technique results in signal enhancements and allows repetition rates faster than those allowed by the carbon C-13 Tl. Therefore, the distortion of relative spectral intensities must always be considered a possibility, and hence quantitative spectra will not always be obtained. 

The development of methods and instrumentation, especially in the high field range, will already open up quite new areas of uses already in the near future. These may at least partly replace and complete solid-state vibration spectroscopy in the polymer field in cases where the amount of material is not the limiting factor. As far as we are able to predict the future, the development of exact quantitative methods of analysis, in particular, will rapidly develop to a high degree of accuracy. 

Shi et al.71 have assigned the backbone and side-chain chemical shifts for 103 of 238 residues of proteorhodopsin using solid state NMR spectroscopy. Analysis of the chemical shifts has allowed determination of protonation states of several carboxylic acids as well as boundaries and distortions of trans-membrane a-helices and secondary structure elements in the loops. It has been shown that internal Asp227, making a part of the counterion, is ionised, while Glul42 located close to the extracellular surface is neutral. 

Solid-state NMR spectroscopy was used for studying the formation of cubic mesoporous aluminophosphate thin films and powders. The analysis of the initial gel, the as-deposited materials and the thermally-treated materials elucidated the changes in the coordination of phosphorus and aluminium atoms and thus revealed how the framework formation and condensation proceeds. The consolidation process in thin films was different than the process in powders. Most probably this could be attributed to the effect of glass substrate. 

Crosslinked polymer networks formed from multifunctional acrylates are completely insoluble. Consequently, solid-state nuclear magnetic resonance (NMR) spectroscopy becomes an attractive method to determine the degree of crosslinking of such polymers (1-4). Solid-state NMR spectroscopy has been used to study the homopolymerization kinetics of various diacrylates and to distinguish between constrained and unconstrained, or unreacted double bonds in polymers (5,6). Solid-state NMR techniques can also be used to determine the domain sizes of different polymer phases and to determine the presence of microgels within a poly multiacrylate sample (7). The results of solid-state NMR experiments have also been correlated to dynamic mechanical analysis measurements of the glass transition (1,8,9) of various polydiacrylates. 

R. Vehring, Red-excitation dispersive Raman spectroscopy is a snitable techniqne for solid-state analysis of respirable pharmaceutical powders, Appl. Spectrosc., 59, 286-292 (2005). 

K. Pollanen, A. Hakkinen, S-P. Reinikinen, J. Rantanen, M. Kaijalainen, M. Louhi-Kultanen and L. Nystrom, IR spectroscopy together with multivariate data analysis as a process analytical tool for in-hne monitoring of crystallization process and solid-state analysis of crystalline product, J. Pharm. Biomed. Anal., 38, 275-284 (2005). 

Characterization of 6 by solid-state NMR spectroscopy as well as elemental analysis (only 28% decrease of rhodium content in samples after 20 cycles in the hydrosilylation) are convincing evidence of the high efficiency of surface rhodium siloxide complexes in the hydrosilylation of carbon-carbon multiple bonds as well as, presumably, in other reactions catalyzed by late transition metal siloxides syn-... 

In a first apphcation of general interest, fluorenyllithium complexes (1, Scheme 1) were studied by solid state NMR spectroscopy. One reason for the choice of this system was that the results from the X-ray investigation presented at that time and solution NMR investigations were in conflict. The bis-quinuchdine complexes investigated in the solid state by X-ray analysis show that the lithium cation is asymmetrically positioned relative to the carbon framework of the anion, mainly interacting in a fashion with carbons C-1, C-9a and C-9 (Figure 9) . 

Both solution-state and solid-state NMR spectroscopy are important analytical tools used to study the structure and dynamics of polymers. This analysis is often limited by peak overlap, which can prevent accurate signal assignment of the dipolar and scalar couplings used to determine structure/property relationships in polymers. Consequently, spectral editing techniques and two- or more dimensional techniques were developed to minimize the effect of spectral overlap. This section highlights only a few of the possible experiments that could be performed to determine the structure of a polymer. 

For catalytic application it is necessary to incorporate hetero-atoms into the silica framework. Several samples have been synthesised using different aluminia precursors. The metal content was determined by X-ray fluorescence analysis, UV-VIS spectra, IR spectra and solid state NMR spectroscopy, respectively. X-ray fluorescence analysis provides information about the metal content of the samples. By variation of the metallic precursor concentration the metal content of the product could be enhanced up to 10 % w/w. 

For formulated products an essential analysis is the assay for API content. This is usually performed by HPLC, but Raman spectroscopy can offer a quantitative analytical alternative. These applications have been extensively researched and reviewed by Strachan et al. [48] and provide over 30 literature references of where Raman spectroscopy has been used to determine the chemical content and physical form of API in solid dosage formulations. As no sample preparation is required the determination of multiple API forms (e.g. polymorphs, hydrates/solvates and amorphous content) provides a solid state analysis that is not possible by HPLC. However, as previously discussed sampling strategies must be employed to ensure the Raman measurement is representative of the whole sample. A potential solution is to sample the whole of a solid dosage form and not multiple regions of it. As presented in Chap. 3 the emerging technique of transmission Raman provides a method to do just this. With acquisition times in the order of seconds, this approach offers an alternative to HPLC and NIR analyses and is also applicable to tablet and capsule analysis in a PAT environment. 

Solid-state NMR spectroscopy is arguably the most commonly applied NMR technique in the study of NOM structure because whole soil or sediment analysis can be performed without sample extraction. The 13C nucleus is typically the focus of NOM solid-state NMR studies because strong 1H-1H dipolar interactions (which cannot be easily overcome experimentally) in the solid state result in extremely broad lines. However, because the natural abundance of the 13C isotope is only -1.13% of the total carbon present, observing 13C signals directly is often difficult. 

The usual difficulties in structurally characterizing crosslinked materials are mainly related to their insolubility in the usual organic solvents. Solid-state FTIR spectroscopy is the most convenient analysis to perform several acute techniques allow accurate measurements to be obtained for several kinds of polymers including nadimide end-capped oligomers [30]. Nevertheless, only fragmentary structural information is obtained the attendance in the network of some functional groups can be evidenced. However, it is not possible to determine exactly the polymer microstructure by FTIR. 

On the basis of several analytical studies (differential thermal analysis, fluorescence, CPMAS solid-state NMR spectroscopy and others) [56-58] two models have been proposed to describe the structure of HCN-polymers, the Umemoto [59] and the Volker models [60]. In the Volker model, HCN polymerizes to extensive double-ladder rod-like structures, while a simpler mono-ladder pattern was hypothesized by Umemoto (Fig. 1). Irrespective of the structure assumed by HCN-polymers, a large panel of purine, imidazole and pyrimidine derivatives can be obtained by hydrolysis of these materials. In 1963, Lowe described the first example of acidic hydrolysis of the HCN-polymer (boiling 6.0 N HC1) to yield amino acids, carboxylic acids, adenine and hypoxanthine (Scheme 4). 

The use of phosphorus-based flame retardants in combination with other, better established, flame retardants is most effective in situations in which the combination proves synergistic. However, as yet our understanding of such synergistic effects is far from complete and more fundamental work is required in this area Work in which the gaseous and solid products of combustion, with and without the presence of flame retardants, are carefully analyzed. Such analyses can now be undertaken more readily than in the past, owing to the relatively recent development of techniques such as gas-phase FT-infrared spectroscopy and laser-pyrolysis time-of-flight mass spectrometry for the identification of volatiles, and solid-state NMR spectroscopy and x-ray photoelectron spectroscopy for the analysis of chars. 

Polymorphism is customarily monitored by melting point or infrared spectral analysis. However, other methods, such as X-ray diffraction, thermal analytical, and solid-state Raman spectroscopy, also can be used. It is expected that the sponsor will conduct a diligent search by evaluating the drug substance recrystallized from various solvents with different properties. Either the basis for concluding that only one crystalline form exists, or comparative information regarding the respective solubilities, dissolution rates, and physical/chemical stability of each crystalline form should be provided. 

In conclusion, it has been shown that the predicted order of miscibility in composite latex particle systems is not necessarily bourne out when the extent of miscibility is guaged by dynamic mechanical analysis, and, very recently, by the same authors using solid-state NMR spectroscopy. Control over particle morphology, and, hence, over damping behaviour can be exercised by the differences in hydrophilicity between the polymer pair in question, by the degree of crosslinking in the first network and by whether or not the first-formed polymer is above or below its Tg when the second monomer is polymerised. 

Si Solid State NMR Spectroscopy. Si solid state NMR spectra for the methanol series of uptakes affected by both procedures A and B were obtained with a Bruker MSL-200 spectrometer. Membrane samples were immersed in liquid nitrogen and subsequently ground with mortar and pestle. Particle sizes sufficient for NMR analysis resulted within three such cooling-grindings. Particulation was more easily accomplished with the high uptake membranes as they were already brittle. 

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