Molecular shape complementarity analysis

This generalization of the Centrally Inverted Map Method (CIMM) of molecular shape complementarity analysis [2] to FIDCOs of functional groups replaces the problem of complementarity evaluation with a conceptually and computationally simpler similarity evaluation. 

This Centrally Inverted Map Method (CIMM) of molecular shape complementarity analysis allows one to use the techniques of similarity measures. In fact, the problem of shape complementarity is converted into a problem of similarity between the original (a,b) parameter map of shape groups HP (a,b) of molecule M] and the centrally inverted (a,b) parameter map of the complementary HP2-ii(a,b) shape groups of molecule M2. 

Besides immediate practical applications in fields such as drug design, molecular surfaces contribute to the transformation of modernizing the conceptual arsenal of chemistry, long dominated by line drawings of chemical bonds of structural formulas. Molecular surfaces have led to a true appreciation of the three-dimensional aspects of molecules, important in all branches of chemistry. Precise methods for the analysis of the shapes of these surfaces are available using the topological shape codes and provide tools for the numerical evaluation of such elusive but important properties as measures of molecular similarity and shape complementarity. 

Figure 7.1.4. The scheme of formation of [2.2.2]cryptand. marked the start of molecular recognition studies. As described in Chapters 2 and 3, the Pedersen analysis was later extended by Lehn s studies of the complementarity of sizes and shapes ofthe cryptand cavities and their guests, and by Cram s preorganization studies. In general, crown ethers and cryptands exhibit analogous complexation behaviour. Thus, similarly to the former host molecules, cryptands in the free, uncomplexed state elongate the vacant cavity by rotating a methylene group inward. Thus, the N...N distance in [2.2.2]-cryptand 54 across the cavity is extended to almost 70 pm [18] whilst, in the complexed...

It is now possible to analyze macromolecular electron densities at a resolution far exceeding the resolution of current x-ray diffraction and other experimental and macromolecular computational techniques. The MEDLA method presents a new perspective for the analysis of global and local shape, molecular similarity, and complementarity. 

The above topological shape analysis techniques can replace visual shape comparisons of molecular models on the computer screen with precise, reliable, and reproducible numerical comparisons of topological shape codes. These comparisons and the similarity or complementarity rankings of molecular sequences can be performed by the computer automatically. This eliminates the subjective element of visual shape comparisons, a particularly important concern if large sequences (e.g. several thousands) of molecules are to be compared. In the data banks of most drug companies there is information stored on literally hundreds of thousands of molecules, and their detailed shape analysis by visual comparison on a computer screen is clearly not feasible. By contrast, automatic, numerical, topological shape analysis by computer is a viable alternative. 

Although the pulse sequences used to study phase transitions are usually quite simple in the examples presented in this review (one to maximum four pulses), the interpretation may be subtle. Solid-state NMR nevertheless remains a difficult technique since quantitative interpretation of the spectra rely on a profound knowledge of the chemical composition and structure of the sample analysis of NMR results also requires a model to relate the observed NMR spectral shapes or relaxation behavior to hypothesis concerning the structure and dynamics of the atoms or molecules carrying spins. That NMR motionally average the atomic and molecular displacements that occur on a time-scale faster than 10—8 10—9s is an important point that should be considered in the interpretation of data. In particular, the difference in perception between NMR and X-ray diffraction with regard to fast and slow dynamical disorder in molecular crystals undergoing phase transitions between different polymorphs was illustrated. In fact, the interpretation of NMR data almost always needs the support of other data obtained by different techniques. Therefore, we emphasized the different complementarities with X-ray (or neutron) diffraction, IQNS and other spectroscopic methods to provide, by cross-correlation of the different data, consistent picture of the phase transition. 

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