Entropic activation

Spectroscopic Signatures of Entropic Activation of Hydride Transfer... 

Since the straightening leads to a decrease in entropy that is proportional to the sequence length, it introduces an entropic activation barrier... 

Since its initial discovery in 1928," the Diels-Alder reaction has become one of the most powerful transformations at the disposal of organic chemists and has found applications in countless occasions. This popularity of the Diels-Alder reaction stems from its ability to stereospecifically generate a six-membered ring through the formation of two new CT-bonds, one 7t-bond, and up to four stereocenters in one concerted cycloaddition. The Diels-Alder reaction is well suited for transannular applications because the dienes and dienophiles can be easily incorporated into macrocyclic precursors and the reaction can be accelerated by catalysts or by heating alone. In addition, the macrocyclic environment provides both enthalpic and entropic activation for reactions that may not readily occur under intermolecular or other intramolecular settings. This allows for efficient generation of complex polycyclic compounds from relatively simple macrocyclic substrates. ... 

The examples described in this chapter bear testimony to the power of transannular reactions in complex natural product syntheses. A wide range of transformations has been applied in transannular settings. These reactions frequently occur with high stereoselectivity and high efficiency compared with their intermolecular or intramolecular counterparts in the synthesis of polycyclic compounds. These are the results of restricted conformations of the macrocyclic substrates that, when appropriately used, lead to spectacular stereoselectivity and impressive reaction acceleration through entropic activation. 

In the case of the retro Diels-Alder reaction, the nature of the activated complex plays a key role. In the activation process of this transformation, the reaction centre undergoes changes, mainly in the electron distributions, that cause a lowering of the chemical potential of the surrounding water molecules. Most likely, the latter is a consequence of an increased interaction between the reaction centre and the water molecules. Since the enforced hydrophobic effect is entropic in origin, this implies that the orientational constraints of the water molecules in the hydrophobic hydration shell are relieved in the activation process. Hence, it almost seems as if in the activated complex, the hydrocarbon part of the reaction centre is involved in hydrogen bonding interactions. Note that the... 

Many other parepistemes were stimulated by the new habits of precision in theory. Two important ones are the entropic theory of rubberlike elasticity in polymers, which again reached a degree of maturity in the middle of the century (Treloar 1951), and the calculation of phase diagrams (CALPHAD) on the basis of measurements of thermochemical quantities (heats of reaction, activity coefficients, etc.) here the first serious attempt, for the Ni-Cr Cu system, was done in the Netherlands by Meijering (1957). The early history of CALPHAD has recently been... 

The natiue of the rate constants k, can be discussed in terms of transition-state theory. This is a general theory for analyzing the energetic and entropic components of a reaction process. In transition-state theory, a reaction is assumed to involve the formation of an activated complex that goes on to product at an extremely rapid rate. The rate of deconposition of the activated con lex has been calculated from the assumptions of the theory to be 6 x 10 s at room temperature and is given by the expression ... 

What are the essential features of surfactant systems An important ingredient is obviously the repulsion between water and nonpolar molecules or molecule parts, the hydrophobic force. This interaction is however highly nontrivial, and its analysis is still an active field of research [4,22,23]. Qualitatively, it is usually attributed to the strong orientational and positional correlations between nonpolar molecules in solution and the surrounding water molecules. The origin of the interaction is therefore entropic free water forms a network of hydrogen bonds. In the neighborhood... 

Although the basic concept of macromolecular networks and entropic elasticity [18] were expressed more then 50 years ago, work on the physics of rubber elasticity [8, 19, 20, 21] is still active. Moreover, the molecular theories of rubber elasticity are advancing to give increasingly realistic models for polymer networks [7, 22]. 

Thus the apparent rate constant (kcat/KM) is determined by the apparent activation barrier Ag. In fact, both Ag and Agjfat should have been written as AG and AGaat, respectively [see eq. (2.11)], but as long as we do not have large entropic effects (see Chapter 9), the approximation given above is reasonable. 

In exploring the entropic difference between a given enzyme and its reference solvent cage, we should consider the dependence of the activation barrier on the activation entropy using the relationship... 

FIGURE 9.5. The potential surface for the 0"C = 0— 0-C-0" step in amide hydrolysis in solution, where the surface is given in terms of the angle 0 and the distance b. The heavy contour lines are spaced by fi (at room temperature) and can be used conveniently in estimating entropic effects. The figure also shows the regions (cross hatched) where the potential is less than for the corresponding reaction in the active site of subtilisin. 

In view of the arguments presented in this chapter, as well as in previous chapters, it seems that electrostatic effects are the most important factors in enzyme catalysis. Entropic factors might also be important in some cases but cannot contribute to the increase of kcJKM. Furthermore, as much as the correlation between structure and catalysis is concerned, it seems that the complimentarity between the electrostatic potential of the enzyme and the change in charges during the reaction will remain the best correlator. Finally, even in cases where the source of the catalytic activity of a given enzyme is hard to elucidate, it is expected that the methods presented in this book will provide the crucial ability to examine different hypothesis in a reliable way. 

Examples of entropically driven systems will be those employing chirally active stationary phases. 

---