Conformational and chemical reactivity

The relationship between conformation and chemical reactivity was first pointed out by D.H.R. Barton in 1950. In a paper he drew attention to the difference in chemical behavior when substituents were placed hi equatorial and axial properties in cyclohexanes. This will become clear from some of the following examples ... 

Disubstituted Cyclohexanes Conformational Energies of Substitutents Conformation and Chemical Reactivity Six Membered Heterocyclic Rings Cyclooctane and Cyclononane Cyclodecane... 

The question is to determine how far these different factors (configuration, conformation and chemical reactivity of the monomeric unit and macromolecular conformation) intervene in the explanation of the modifications of the COTTON effects resulting from changes in external conditions. 

In some situations, the direct attachment of a large group (such as fluorescamine) to a biologically active substrate can reduce activity. This is due to steric hindrance which can cause a change in conformation or physically block an active site. This condition can be obviated in many cases by attaching the bulky moiety to a spacer arm composed of two or more methylene groups. To this end, a variant of F-D was also synthesized in which a spacer arm of beta-alanine was inserted between the fluorescent and chemically reactive moieties of the reagent. 

However, it cannot be assumed that this initial binding is the same as the final conformation that the protein and substrate adopt during actual substrate attack. b)The final stages of the cycle, when the geometry and chemical reactivity of this complex determine the structure of the metabolite produced. 

Pioneering work in the field of conformational analysis was contributed by O. Hassel (Norway) and D. R. H. Barton (Britain), for which they shared the Nobel Prize in chemistry in 1969. Hassel s work involved the physical determination of preferred conformations of small molecules, whereas Barton was the first to show the general importance of conformation to chemical reactivity. Study of conformations and conformational equilibria has direct application to explaining the extraordinary specificity exhibited by com-... 

The changes in sedimentation coefficient and chemical reactivity caused by PALA fit the model that the enzyme exists in two distinct conformations (T and R) and that the binding of PALA to only one or two of the c subunits causes the entire c6r6 complex to flip from the T to the R state. The dissociation constant for PALA is higher in the T state than in the R state. The equilibrium constant L = [T]/[R] has been calculated to be 250 in the absence of substrates and... 

Hammarstrom, P., Owenius, R., Martenson, L-G., Carlsson, U., and Lindgren, M. (2001) High resolution probing of local conformational change in proteins by the use of multiple labeling unfolding and self -assembly of human carbonic anhydrase II monitored by spin, fluorescent, and chemical reactivity probs, Biophys. J. 80, 2867-2885. 

Shevchenko, S. M., T. J. Elder, S. G. Semenov, andM. Ya.Zarubin. 1995. Conformational effects on the electronic structure and chemical reactivity of lignin model p-quinone methides and benzyl cations. Res. Chem. Inter. 21(3-5) 413 23. 

Finally, mention should be made of the increasing application of the intramolecular Nuclear Overhauser Effect (NOE) which has played an important role not only as an aid to structural elucidation but also in the conformational determination of some of the germacrane sesquiterpenes. These results have a significant bearing on the understanding of transannular effects and chemical reactivity. 

The single bond linking the atoms is of a fixed length, but the atoms are free to rotate around the bond. A molecule can have many different conformations because of this bond rotation. The conformation of large molecules is important as it influences physical properties and chemical reactivity. 

The study of the chemical and physical properties of different conformations of organic compounds is called conformational analysis. To understand the relationship between structure and physical properties, we need to know how structural differences change the conformations of molecules, and which conformations predominate at equilibrium. To understand the relationship between structure and chemical reactivity, we must know the energy difference between the most stable conformation and the conformation required to bring atoms into proximity for reaction. If a substantial conformational change is required to prepare a molecule for reaction, then the energy associated with that change affects the rate of the reaction. 

The same arguments can be applied to other energetically facile interconversions of two potential reactants. For example, many organic molecules undergo rapid proton shifts (tautomerism), and the chemical reactivity of the two isomers may be quite different It is not valid, however, to deduce the ratio of two tautomers on the basis of subsequent reactions that have activation energies greater than that of the tautomerism. Just as in the case of conformational isomerism, the ratio of products formed in subsequent reactions will not be controlled by the position of the facile equilibrium. 

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