Geometry of small molecules

GAs or other methods from evolutionary computation are applied in various fields of chemistry Its tasks include the geometry optimization of conformations of small molecules, the elaboration of models for the prediction of properties or biological activities, the design of molecules de novo, the analysis of the interaction of proteins and their ligands, or the selection of descriptors [18]. The last application is explained briefly in Section 9.7.6. 

Step 1 of the parametrization process is the selection of the appropriate model compounds. In the case of small molecules, such as compounds of pharmaceutical interest, the model compound may be the desired molecule itself. In other cases it is desirable to select several small model compounds that can then be connected to create the final, desired molecule. Model compounds should be selected for which adequate experimental data exist, as listed in Table 1. Since in almost all cases QM data can be substimted when experimental data are absent (see comments on the use of QM data, above), the model compounds should be of a size that is accessible to QM calculations using a level of theory no lower than HE/6-31G. This ensures that geometries, vibrational spectra, conformational energetics, and model compound-water interaction energies can all be performed at a level of theory such that the data obtained are of high enough quality to accurately replace and... 

The rate of radical addition is most dramatically affected by substituents either at the site of attack or at the radical center. Remote substituents generally have only a small influence on the stereochemistry and regiospecificity of addition unless these groups are very bulky or the geometry of the molecules is constrained (e.g. intramolecular addition - Section 1,2.4). 

If the electronegativity of the ligands X is much less than the electronegativity of the central atom A, the electrons in the valence shell of A are not well localized into pairs and therefore have a small or zero effect on the geometry. In such molecules the bonds are very ionic in the sense A X+, and the central atom A is essentially an anion with a spherical electron density distribution. In this case the VSEPR model is not valid, and the geometry of the molecule is determined by ligand-ligand repulsions. 

Then, the basis set has to be selected. Let s take as an example the amino acid alanine. It is a small enough system so that a fairly large basis set could be used, such as 6-31G. Suppose one is interested in the optimum geometry of the molecule, as obtained at Hartree-Fock level and at the energy corresponding to this geometry. Then, geometry optimization has to be performed so the card will read ... 

Semi- and nonempirical MO calculations involving complete geometry optimization are now being developed for simulating chemical reactions of small molecules (238,239). 

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