Crystal structure prediction assumption

In the secondary distribution of the elements in the Upper Mantle and Crust, Goldschmidt believed that during the formation of a crystalline phase the principal factor controlling the behaviour of an element is the size of its ions. From tables of ionic radii one could predict the crystal structures in which a given ion was most likely to occur. This concept has immense qualitative value in crystal chemistry, and has been remarkably successful in view of the assumptions... 

Asymmetric Diels-Alder reactions have been the subject of some of the more thorough mechanistic studies. Fairly reliable structural models for predicting the outcome of these reactions exist. In a review of the subject, it has been suggested that the stereochemical course of the reaction of a variety of chiral acrylates could be consistently predicted based on two models (Figures 39 and 40). Model A positions the complex in a (Z)-syn-s-trans conformation and presumes attack from the least-hindered face of the double bond. This model is consistent with almost all of the structural data for systems of this type (e.g. SnCWethyl cinnamate X-ray diffraction study). Contrapuntally, the large number of experimental observations that can be explained by this model support the assumption that the crystal structure conformation (26) is relevant to the course of these reactions. 

The main structural features of compound 1 are the seven-membered ring and the orientation of the dimethylallyl group. We believe that it is not possible by calculation accurately to predict the exact conformation of the side chain the usefulness of a crystal structure is also limited concerning this flexible group. The seven-membered ring contains three planar atoms and has some similarity with cyclohexene we expect therefore the existence of two conform-ers that are related to the two twist forms of cyclohexene. A conformational analysis using MNDO [5] supports this assumption. For our model we have used the conformer with the lowest MNDO heat of formation, which is also in agreement with a published X-ray structure of a chloro derivative of TIBO [6]. 

Another way to predict protein-SM interactions is to assume that similar protein sequences bind similar SMs. This is a simple, yet powerful assumption, providing accurate interaction predictions, demonstrated in a number of studies. The actual implementation of this idea into a computational algorithm is limited only by human imagination and available time, so its discussion is beyond the scope of this chapter. One interesting sequence-based interaction prediction approach reported by Synder and co-workers [61] was used to create the small-molecule interaction database (SMID) (Fig. 2-12). Biologically relevant SMs were determined from three-dimensional x-ray crystal structures containing... 

The experimentally determined (S)/(R)-ratio of 18/82 was compared with the relative stabilities of the two diastereomeric products ([Co((S),(S)-ppm)((R)-ala)] / [Co((S),(S)-ppm)((S)-ala)] ), calculated by strain-energy minimization. The reported strain energies, based on a single conformer for each of the two diastereomeric products (identical to the crystal structure of the complex with coordinated (R)-alanine [328]), are in good agreement with the experimentally determined data (23/77 versus 18/82). A full conformational analysis led to a ratio of 30/70 when only conformational flexibility is allowed, or 33/67 when other isomers were also included in the analysis [294]. The assumption in the original report was that the enantio-selectivity is based on the relative energies of the diastereomeric forms of the cobalt(III) products [327]. Fortunately, a qualitatively similar result is expected if the stereoselectivity is controlled by the deprotonated intermediates. However, a quantitatively accurate prediction of the product ratio is not expected in this case. 

The ultimate goal is to determine the crystal structures in which a molecule may crystallize and then to predict the physical properties without recourse to experiment. Attempts have been made to calculate the crystal structure directly from the molecular structure of the drug [100,101]. The basic assumptions are that real crystal structures have relatively low lattice... 

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