Conformational isomers, definition

As a general rule we have preferred to maintain the widely accepted definition of conformational isomers in terms of X,0-cis and X,0-trans terms, instead of standard E, Z formalism, to which reference will be also made when more appropriate. 

Apart from the ill-definitiveness of the inverse vibrational problem two principal objections are usually posed against the standard VFF model [5], First, the neglect of the long range interactions is not always physically justified and often contradicts with the real electronic structure of the molecule under study. Second, the transferability of force-constants is still a disputable topic, especially when the force-constants are transferred between neutral molecules and the corresponding ionized forms, or between conformational isomers [6, 7],... 

Quite definitive results were obtained when mixtures of the halides were considered, and the authors deduced that there were two distinct types of hahde anion binding sites a-sites which bind Cl and F and 8-sites which bind Br and I . Other anions introduce more complex behavior but the data obtained suggested that OCN, Ni and CN all bind at or near a-sites though possibly to different intermediate forms of the enzyme (presumably different forms may involve overall differences in the valence of the Cu atoms). As suggested above, ceruloplasmin is conformationally sensitive to specific ions and it is quite possible that at least part of the complex behavior observed with the various inhibitors may be due to a shifting of the enzyme among two or more conformational isomers. 

We will now discuss at some length the many ways in which deviations from standard bonding parameters lead to energetic destabilization of a molecule. We will focus on "stable" structures (i.e., not on reactive intermediates), but the notions we develop here also apply to reactive intermediates. We first explore acyclic systems, wherein molecular motions directly lead to strained forms. Note that we are not yet considering conventional chemical reactivity. We will be considering conformers, or conformational isomers. Recall that conformers are stereoisomers that interconvert by rotation around single bonds (see Chapter 6 for definitions of stereochemical concepts). These isomers are not to be confused with constitutional isomers, where the molecular formula is the same, but the atoms are arranged differently. 

The last example is somewhat more complicated since four isomers (two tautomers and two conformations) are present at equilibrium (Figure 9) (78BSB189). The experimental value (3.73 D, Table 3) establishes the predominance of the 3-azido tautomer but does not allow the determination of the conformational equilibrium other methods (Section 4.04.2.3.4(v)) are necessary to establish definitely the Z conformation (43b). 

The study of optical isomers has shown a similar development. First it was shown that the reduction potentials of several meso and racemic isomers were different (Elving et al., 1965 Feokstistov, 1968 Zavada et al., 1963) and later, studies have been made of the ratio of dljmeso compound isolated from electrolyses which form products capable of showing optical activity. Thus the conformation of the products from the pinacolization of ketones, the reduction of double bonds, the reduction of onium ions and the oxidation of carboxylic acids have been reported by several workers (reviewed by Feokstistov, 1968). Unfortunately, in many of these studies the electrolysis conditions were not controlled and it is therefore too early to draw definite conclusions about the stereochemistry of electrode processes and the possibilities for asymmetric syntheses. 

Note Refer to the text for definitions of conformations. AC is the relative energy for conformations of a given isomer, AE is the energy measured relative to the Bda conformation of the adduct formed by trans addition of the syn isomer. The reaction coordinates R, a, 3, Ys 5, and e are defined in Figure 3. 

As a final example, we consider the relative stability of the torsional isomers of 2-butene. The six conformations of 2-butene are shown below along with the definitions to be used in the discussion, e.g. the label Css refers to the cis isomer where the in plane hydrogens of the methyl groups are staggered relative to the double bond. 

Concomitant with these developments in spectroscopy, thermochemists were finding that, to a reasonable approximation, molecular enthalpies could be determined as a sum of bond enthalpies. Thus, assuming transferability, if two different molecules were to be composed of identical bonds (i.e., they were to be isomers of one kind or another), the sum of the differences in the strains of diose bonds from one molecule to the other (which would arise from different bond lengths in the two molecules - the definition of strain in this instance is the positive deviation from the zero of energy) would allow one to predict the difference in enthalpies. Such prediction was a major goal of the emerging area of organic conformational analysis. 

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