Energies and Conformations

Due to the noncrystalline, nonequilibrium nature of polymers, a statistical mechanical description is rigorously most correct. Thus, simply hnding a minimum-energy conformation and computing properties is not generally suf-hcient. It is usually necessary to compute ensemble averages, even of molecular properties. The additional work needed on the part of both the researcher to set up the simulation and the computer to run the simulation must be considered. When possible, it is advisable to use group additivity or analytic estimation methods. 

The chloro- and bromo-cyclohexane inclusion compounds have been extensively examined by infrared (4000-30 cm-1) spectroscopy65-68 and by Raman (< 1000 cm-1) spectroscopy 69). In the canals both guests are found to exist exclusively in the chair conformation with an axial halogen substituent, while iodocyclohexane 65, 68,69) acj0pts both axial and equatorial conformations in the canal. These results should be contrasted with the familiar situation in the liquid phase where the equatorial arrangement is the lowest energy conformer and is present to the extent of about 65-70% at room temperature. 

Currently there is only one product that adopts this approach and this is NMRPredict from Modgraph. It is based on the work by Prof. Ray Abraham at the University of Liverpool (UK). This approach calculates chemical shifts for a range of low energy conformers and averages them to give a net chemical shift. This approach seems to offer the most accurate prediction of chemical shift but the disadvantage is that it is very slow (particularly for conformationally flexible molecules). 

The success of the gas phase electron diffraction analysis of cis-and /ra 5-decalin (123) is another example of the use of MM calculations as an auxiliary technique. Minimum energy conformations and vibrational ampUtudes were calculated by both the Lifson and Boyd force fields (30,31) and were used as the starting values for refinement of the geometrical and vibrational parameters for the least-squares analysis. The results revealed no appreciable strain in cj5-decalin (123) other than that expected from gauche interactions. 

Table 2. Minimum energy conformations and conformer populations for a series of glucos-phyngolipids and glucoglycerolipids. Values are obtained by MM3 minimizations at a value of dielectric constant e=4 [ 151 ] 9 V ei ...

Unlike other pharmacophore identification routines, the conformational search is performed on-the-fly in GASP and represents an integral part of the program. Each compound is input a single, low-energy conformation and random rotations and translations are applied in order to explore the conformational variation prior to superposition. 

Two classical methods are available in THINK to perform the conformational expansion of molecules systematic search and random search. When the systematic search option is used, the use of contacts check avoids high-energy conformations and reduces the overall processing time. The random method uses a random number generator to select the conformations from within the estimated total number of conformations. The implementation of the program does not prohibit identical conformations to be output resulting from symmetry. These conformations are used in the pharmacophore generation and site search modules. 

There is no reason, other than stereoelectronic dogma, for ruling out conformer [46b], Moreover, there is also no reason for assuming that the coenzyme reacts through the lowest energy conformer, and so conformers [46c] and [46d] are at least possible in principle. 

From the previous sections on theoretical and spectral aspects of 1,3-dioxolanes, it is clear that the ring is conformationally labile and the data are best explained in terms of a freely pseudorotating system with a small energy barrier between conformers (B-80MI43001). The half-chair (39) and envelope (40) forms are the two lowest-energy conformers and it is the interconversion of these structures which best describes the pseudorotation (75JA1358). The X-ray structure of (1) shows the dioxolane ring has a conformation mid-way between these forms. 

Only two of them, boxed in yellow, place the large Ph group perpendicular to the carbonyl group. These yellow boxed conformations are therefore the lowest-energy conformers and, for the purpose of the discussion that follows, they are the only ones whose reactions we need to consider. 

---