The Concept of Conformation

D. H. R. Barton (Imperial College, London) and O. Hassel (Oslo) development of the concept of conformation and its application in chemistry. 

Application of the concept of conformational restriction to opioid peptides has produced fruitful results, insofar as peptide analogues and mimetics with interesting opioid activity profiles and high stability against enzymatic... 

Barton, D. H. R. Crich, D. Motherwell, W. B. J. Chem. Soc., Chem. Commun. 1983, 939. Derek Barton (United Kingdom, 1918—1998) studied under Ian Heilbron at Imperial College in his youth. He taught in England, France and the US. Barton won the Nobel Prize in Chemistry in 1969 for development of the concept of conformation. He passed away in his office at the University of Texas at Austin. 

The concept of conformational analysis has led to a better understanding of the spatial arrangements of cyclic alkanes and of the chemical reactivity of functionalized derivatives. A specific terminology is used. 

Real space algorithms (section 4) allow for mappings between present day computer programs and strict molecular quantum mechanics [10,11]. It is the separability of base molecular states that permits characterizing molecular states in electronic Hilbert space and molecular species in real space. This feature eliminates one of the shortcomings of the standard BO scheme [6,7,12]. Confining and asymptotic GED states are introduced. In section 5 the concept of conformation states in electronic Hilbert space is qualitatively presented. 

The concept of conformational isomerism is central to any consideration of molecular shape. Molecules that are flexible may exist in many different shapes or conformers. Conformational isomerism is the process whereby a single molecule undergoes transitions from one shape to another the physical properties of the molecule have not changed, merely the shape. Conformational isomerism is demonstrated by compounds in which the free rotation of atoms around chemical bonds is not significantly hindered. The energy barrier to the transition between different conformations is usually very low... 

The calculated value incorrectly assumes unrestricted free rotation so that all conformations are equally probable. Since most molecules of ethane have the staggered conformation, the structural randomness is less than calculated, and the actual observed entropy is less. This discrepancy led to the concept of conformations with different energies. 

HASSEL, ODD (1897-1981), A Norwegian chemist who won the Nobel pnze for chemistry in I969 with Derek Barton for their contributions to the development of the concept of conformation and its application in chemistry. A great deal of his work was concerned with Using X-ray and electron differentiation methods ol cry stal and molecular structures. He also researched stereochemistry and conformational analysis. His education and leadline career were in his homeland. 

In a series of publications [18-20], the concept of conformation-dependent sequence design (CDSD) of functional copolymers has been introduced (for recent reviews, see [21-25]). The essence of the proposed approach is based on the assumption that a copolymer obtained under certain preparation conditions is able to remember features of the original ( parent ) conformation in which it was built and to store the corresponding information in the resulting chemical sequence. In other words, this concept takes into account... 

With the exception of sterols most membrane lipids are conformationally flexible molecules. The question arises whether the concept of conformational restriction can be extended from peptides to the field of sphingolipids. The observation that conformationally restricted derivatives of myristic acid have selective toxicity towards trypanosomes demonstrates that this strategy is also applicable... 

Any molecule of a given configuration can exist in different spatial arrangements (conformations) when the atoms or atomic groups are rotated or twisted with respect to each other within the limits permitted by the bonds. Although the concept of conformation in carbohydrate chemistry is old (Haworth, 1929), novel studies during the last three decades, especially by Barton and Hassel (Nobel Prize in 1969), have added clarity and important details to this concept. The conformations can best be visualized with the use of molecular models. 

The concept of conformational Probability Density Map often is improperly associated with that of potential energy map. The potential energy map indeed gives a relatively good image of the probability density map of finding a molecule in a given conformation [53,54]. To determine the conformational chemical physic properties of a molecule, as a function of temperature, statistical methods have to be used. 

Ottar, Beckett and coworkers, Reeves, and others " developed the concept of conformational analysis, and ascertained the factors that determine the relative stability of the various conformations. Development of an understanding of conformation and the energy relationships led to rationalization of many experimental observations, and has provided a guide for fruitful research in many areas of organic chemistry. ... 

The concepts of conformation and dynamics developed in Part I—especially those dealing with the specificity and catalytic power of enzymes, the regulation of their catalytic activity, and the transport of molecules and ions across membranes—enable us to now ask questions fundamental to biochemistry ... 

To solve the inactivation issues mentioned above, the concept of conformationally restricted (Z)-fluoro-olefm dipeptide isosteres that mimic the active trans conformation of the DPP IV inhibitors was applied by Welch and co-workers to the preparation of inhibitors having Ala-T fCF CHJ-Pro structure (76 and 78) and their inhibitory activities were evaluated (see Figure 10.6) [36, 37]. DPP IV inhibitory activities and the stability of the inhibitors 76 and 77, in comparison with those of the model dipeptide Ala-Pro derivative 78 are summarized in Table 10.2. These fluoro-olefin analogues, 76 and 77, showed better DPP IV inhibitory activity than that of 78. In particular, u-76 having the same relative stereochemistry as the natural dipeptide (L-Xaa-L-X aa) configurations exhibited potent... 

Since the concept of conformational restriction worked so well, we decided to pursue this idea further, restricting the conformation of tracizoline by carrying out... 

The concepts of conformational analysis are fimdamental to a proper understanding of the relationship between the structure and properties of carbohydrates. The general application of conformational analysis has been stimulated by the relative universality of its fundamental postulates, especially on the qualitative level. The leading notion is the quantification of... 

As an important piece of evidence X-ray investigations of tropine hydrobromide crystals (26) indicated clearly the presence of this form only with the methyl group oriented towards the five-membered ring. All these findings could be fitted in with the concept of conformational analysis (21-25). 

Stereospecific Polymerization. One of the more exciting recent developments in polymerization chemistry is the preparation and the study of isotactic polymers. Isotactic polymers are prepared from well-known monomers with new typies of catalysts. The resultant products are polymers of the same chemical composition and configuration as those prepared with conventional radical-type or ionic catalysts, but of higher crystallinity, higher density, higher melting points, and improved mechanical properties. In order to understand how this can be achieved, it is necessary to introduce the concept of conformation of the polymer chain, as well as of its configuration. 

The isomerism found in sugars necessitated the concept of conformation. The advent of NMR and other techniques which were able to determine the properties of rotational or other stereochemicaUy nonri d molecules raised new problems concerning the definition and limitation of the concept of isomerism. The field of chemical isomerism is an active one, as proved by the several reviews on isomerism [3,6,20], the many recent books on stereochemistry [8 19], and by the award of Nobel prizes to Barton in 1969, and Prelog in 1975. 

O. Hassel for their contribution to the development of the concept of conformation . 

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