Conformational aspects calculations

Figures 17A and 17B (p. 183) show energy as a function of rotation for a series of 1-substituted acetaldehydes, with 6 = 0° in the syn conformation and 6 = 180° in the anti conformation. The calculations were done using the PM3 method. Figure 17A for a vacuum, whereas Fig. 17B is for a solvent cavity with a dielectric constant of 4." The table gives the calculated barriers. Discuss the following aspects (a) rationalize the order Br > Cl > F for syn conformers (b) rationalize the shift to favor the am. conformation in the more polar environment. 

An experimental study of barbituric acid found one new polymorph where molecules in the asymmetric unit adopted two different conformations [10]. The conformational aspect was investigated through the use of ab initio calculations, which permitted the deduction that the new form found would have a lower lattice energy than would the known form. It was also found that many hypothetical structures characterized by a variety of hydrogen-bonding structures were possible, and so the combined theoretical and experimental studies indicated that a search for additional polymorphs might yield new crystal structures. 

In Section lU-B we showed that the chemical shift of methyl carbons in polypropylene can be calculated considering the relative position of the adjacent substituents, expressed in configurational terms (m or r, Oor 1). An alternative interpretation, with a better physical basis, takes into account only conformational aspects. Experimental evidence from hydrocarbon spectra has established that the presence of a gauche conformation between carbon atoms separated by three bonds causes an upfield shift(7 effect) (206). For flexible molecules the magnitude of this shift depends on the fraction of conformers having gauche interactions with the observed carbons (207). 

Computational data enabled charge delocalization modes, substituent effects, and in relevant cases conformational aspects to be addressed, and comparison with experiments were found to be fairly good. Moreover, the calculated relative stabilities of the carbocations correlated reasonably well with the available biological activities. 

Since the properties of any material are related to its structure, the conformational aspect of these studies cannot be neglected. The emphasis of the latter paper (56) was, however, primarily concerned with the electronic structure of the dimeric model compound, and how this information might be compared to experimental facts. Upon completion of the calculations, it began to appear that the results were seriously flawed. It was... 

In order to explain the stereospecificity of the thermally induced cyclization of preisocalamendiol (315) to give dehydroisocalamendiol (316), Terada and Yamamura have carried out molecular mechanics calculations on the ground-state conformers and probable transition states of (315). The computed values of the steric energies of the possible transition states are in good agreement with the observed experimental facts. Other studies related to the conformational aspects of germacrane sesquiterpenoids include an examination of the NOE effects in the isofuranodiene (317), which shows the 1,5-diene system to be in a crossed... 

There is no information available concerning the molecular mechanical calculations and conformational aspects of these heterocycles. 

Often, one needs to compare different 3D structures or conformations of a molecule. That is done internally by the 3D stmcture generation program to weed out too similar conformations of fragments. Another aspect is the need of the computational chemist to compare different generated or experimental structures. A well-established measure is the so-called root mean square (RMS) value of all atom-atom distances between two 3D structures. The RMS value needed here is a minimum value achieved by superimposing the two 3D structures optimally. Before calculating the RMS, the sum of interatomic distances is minimized by optimizing the superimposition in 3D. 

In the case of being successful in calculating multiple conformations by using time- or ensemble-averaged MD restraints the solved molecular structures are presented as 3D models and can be deposited in an electronic structure database (17). Finally, it is recommended to provide an accurate explanation of the procedures used for the structure elucidation because the application of different methods (NMR, DG, MD, SA, Monte-Carlo calculations. X-ray crystallography) may result in varying conformational models which do not implicitly display the real state of a molecule. This aspect should be always kept in mind when dealing with structure determination methods. 

The determination of the three-dimensional conformation of molecules is an important aspect of QSAR, which can be obtained from x-ray crystallography [66], NMR spectroscopy or, in the case of small molecular fragments by quantum-mechanical calculations [67,68]. 

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