Structure elucidation problem, application

In summary, the variety of applications outlined in this section provides evidence for the concept of on-line hyphenation and demonstrates the enormous potential for the solution of structure elucidation problems in all major research areas. 

These steps, ionisation and dissociations, must be carried out in vacuum so as to avoid collisions between the ions of interest and other substances (e.g. neutrals and radicals). Taken together, such a series of unimolecular dissociations are termed fragmentation patterns. They are characteristic of the structural features of the original molecular ion radical, hence the extensive applications of mass spectrometry to structure elucidation problems. 

Because the experimental conditions for production mass spectra are strongly instrument dependent, generally not very well standardized and difficult to exchange between instruments from different manufacturers, there are at present no generally applicable spectral libraries for MS-MS spectra that can assist in structure elucidation problems. 

Although many structure generators have been described in the literature over the past 30 years, the underlying procedures fall into one of two classes structure assembly or structure reduction. Experience has shown that systems based on both have application in structure elucidation problems (see Structure Generators). 

The structure elucidation problem focuses on the relationship between chemical spectra, structure, and additional sub-structural information. The structure generator provides all possible structures consistent with the constraints. If the chemical spectra can be replaced with different restrictions, the structure generator can be utilized for other purposes. For example, the introduction of biologically effective substructures and the distance relations between specific substructures to a structure generator may lead to proposals for new, draft structures in molecular design. Furthermore, these structures can be evaluated by log P values and so on. The structure generator certainly shows potential ability in application fields dependent on the contents of good list, bad list, other structural requirements, and the evaluation items. 

GC-AAS has found late acceptance because of the relatively low sensitivity of the flame graphite furnaces have also been proposed as detectors. The quartz tube atomiser (QTA) [186], in particular the version heated with a hydrogen-oxygen flame (QF), is particularly effective [187] and is used nowadays almost exclusively for GC-AAS. The major problem associated with coupling of GC with AAS is the limited volume of measurement solution that can be injected on to the column (about 100 xL). Virtually no GC-AAS applications have been reported. As for GC-plasma source techniques for element-selective detection, GC-ICP-MS and GC-MIP-AES dominate for organometallic analysis and are complementary to PDA, FTIR and MS analysis for structural elucidation of unknowns. Only a few industrial laboratories are active in this field for the purpose of polymer/additive analysis. GC-AES is generally the most helpful for the identification of additives on the basis of elemental detection, but applications are limited mainly to tin compounds as PVC stabilisers. 

Nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research has been used primarily in a classical, organic chemistry framework. Typical studies have included (1) the structure elucidation of compounds [1,2], (2) investigating chirality of drug substances [3,4], (3) the determination of cellular metabolism [5,6], and (4) protein studies [7-9], to name but a few. From the development perspective, NMR is traditionally used again for structure elucidation, but also for analytical applications [10]. In each case, solution-phase NMR has been utilized. It seems ironic that although —90% of the pharmaceutical products on the market exist in the solid form, solid state NMR is in its infancy as applied to pharmaceutical problem solving and methods development. 

Since the late 1950s PMR spectroscopy has contributed immensely to many areas of the chemistry of alkaloids (7). With the advent of Fourier transform spectrometers CMR has rapidly approached the level of PMR in its application to problems of structural elucidation and stereochemistry. In the case of the alkaloids many classes of the isoquinoline family have been studied. These alkaloids are of particular interest not only because of their widespread occurrence in nature but also because of their pharmacological activity (2-5). Wenkert et al. (6) were the first to review progress in this area. More recently, Shamma and Hindenlang (7) have made an extensive compilation of chemical shift data on amines and alkaloids that includes many... 

Solid State (SS) NMR is a spectroscopic technique which can answer most of these questions for any solids crystalline, polycrystalline, amorphous phases, glasses, etc. Thus the growing popularity of NMR spectroscopy as a tool for structural elucidation of different solid supramolecular assemblies is fully understandable. Ripmeester and Ratcliffe reviewed the literature on applications of solid state NMR in supramolecular chemistry up to 1996 [5] where a short introduction to the theoretical background, experimental NMR techniques, and examples of problems which can be resolved by NMR, are presented. 

Robust automation for structural determinations in combinatorial chemistry [13]. Two-dimensional mass spectrometry [14] could be regarded as the poor cousin of 2D NMR insofar as it has seen little application to real-world problems. This could be a technique that is ripe for exploiting structural elucidation in complex mixtures. 

Triketides are relatively rare. Triacetic acid lactone (4.2) has been detected in Penicillium patulum. It is also produced by fatty acid synthase in the absence of the reductant NADPH. Radicinin (4.3) is a major phytotoxin isolated from Ahernaria radicina (Stemphyllium radicinum) which causes a black rot of carrots. It is also formed by other Ahernaria species. Its pyrano[4,3- ]pyran structure, the identification of which had eluded purely chemical degradative studies, was established in one of the earlier applications of NMR spectroscopy to natural product structure elucidation. The biosynthesis of radicinin from acetate units was studied in 1970 by both radio-isotope methods using carbon-14 and by carbon-13 enrichment studies with NMR methods of detection. This was one of the first applications of this NMR technique to biosynthetic problems. These results established the labelling pattern for radicinin shown in 4.3. 

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