Design structure elucidation

Computational techniques in organic chemistry such as for drug design, structure elucidation or synthesis planning quite often investigate enormous numbers of hypothetical molecules, which are not yet... 

The systematic analysis of chemical information can lead to a computer representation of chemical knowledge. Such knowledge bases can be used in decision-making systems to assist the chemist in the solution of fundamental problems synthesis design, structure elucidation, design of chemical plants, etc. 

After approaches to the solution of the major tasks in chemoinformatics have thus been outlined, these methods are put to work in specific applications. Some of these apphcations, such as structure elucidation on the basis of spectral information, reaction prediction, computer-assisted synthesis design or drug design, are presented in Chapter 10. 

Similarity search appears as an extremely useful tool for computer-aided structure elucidation as well as for molecular design. Here the similarity property principle is involved. This may be stated as ... 

Similarity search appears as an extremely useful tool for computer-aided structure elucidation as well as molecular design. 

An early field of application in analytical chemistry is structure elucidation. DENDRAL was one of the first ES in general, designed to the identification of organic compounds from mass spectrometric data (Buchanan and Feigenbaum [1978]). In the 1980s and 1990s a flood of expert systems has been developed in analytical chemistry for different types of application, viz ... 

While the early days of LC-NMR and LC-NMR-MS were plagued by the poor sensitivity of the NMR spectrometer, the recent probe design advances have provided a means to potentially overcome this hurdle. As reported in the literature, it is possible to get both ID and 2D homo-nuclear and heteronuclear correlation data on sub micrograms of materials in quite complex mixtures utilizing cryogenic flow-probes in tandem with SPE peak trappings [98]. While these technologies are still in their infancy, they have the potential to revolutionize LC-NMR as a structure elucidation technique. 

An orthogonal array design and electronic pressure programming have been described for the optimisation of the GC determination of NP [76]. The characterisation of isomers of technical NP previously reported by Giger et al. [77] was further improved by GC-MS and GC-FTIR [78] identifying 14 isomers. On the other hand, Wheeler et al. [79] indicated the presence of five different groups of isomers of the 22 separated isomers. The isomeric composition of APEO mixtures and their structure elucidation are discussed in more detail in the next section. 

These questions fall into the domains of structure-activity relationships, structure elucidation, and synthesis design, respectively. They all ask for new information not yet known explicitly. That is, they require predictions. 

In this sense, expert systems for the prediction of chemcial reactions for the design of organic syntheses, for the prediction of physical data, for structure elucidation, and for QSAR can be founded on the knowledge base comprized by the models presented here. 

The development of mass spectrometry/mass spectrometry (MS/MS) has provided the chemical analyst with a powerful tool for structure elucidation. The primary goal of this project is to develop the full capacity of triple quadrupole mass spectrometry (TOMS) as a tool for routine structure determination. To accomplish this, we have designed and developed computer data bases for spectra and structures (1,2), programs for matching spectra (3), and procedures... 

Dubois et al. developed the Description, Acquisition, Retrieval, Computer-aided design-Elucidation by Progressive Intersection of Ordered Structures (DARC-EPIOS) system for structural elucidation.Their approach was based on C spectra. These were predicted using an additive method, but based on their DARC descriptor of environment, as opposed to the more common HOSE code. The EPIOS system was designed to take account of the diagnostic (or not) nature of the C spectrum with respect to environment, i.e., depending on the specific sub-structures. 

Chemical shift correlated NMR experiments are the most valuable amongst the variety of high resolution NMR techniques designed to date. In the family of homonuclear techniques, four basic experiments are applied routinely to the structure elucidation of molecules of all sizes. The first two, COSY [1, 2] and TOCSY [3, 4], provide through bond connectivity information based on the coherent (J-couplings) transfer of polarization between spins. The other two, NOESY [5] and ROESY [6] reveal proximity of spins in space by making use of the incoherent polarization transfer (nuclear Overhauser effect, NOE). These two different polarization transfer mechanisms can be looked at as two complementary vehicles which allow us to move from one proton atom of a molecule to another proton atom this is the essence of a structure determination by the H NMR spectroscopy. 

Remarkably, in this context, no significant sequence homology of amino acid residues could be detected. This successful structure elucidation should allow the design of non-natural specific inhibitors of this enzyme on the basis of structural information known from the bulgecins. 

---