Stabilization of Transition States

Cross-interaction constants and transition-state structure in solution, 27, 57 Crown-ether complexes, stability and reactivity of, 17,279 Crystallographic approaches to transition state structures, 29,87 Cyclodextrins and other catalysts, the stabilization of transition states by, 29,1... 

Generally speaking, the influence of solvent on reaction rates (equilibria) is determined by the difference between the effects < n the stability of transition states (products) and reactants. According to what Leffler and Grunwald (1963) call the first approximation, the free energy of a solute molecule RX is given by the sum of internal and solvent contributions, as shown in (59). The... 

Conducting reactions in nanospace where the dimensions of the reaction vessel are comparable to those of the reactants provides a new tool that can be used to control the selectivity of chemical transformations.1 This dimensional aspect of nano-vessels has been referred to as shape selectivity.2 The effect of spatial confinement can potentially be exerted at all points on the reaction surface but its influence on three stationary points along the reaction coordinate (reactants, transition states, and products) deserve special attention.3,4 (1) Molecular sieving of the reactants, excluding substrates of the incorrect dimension from the reaction site can occur (reactant selectivity). (2) Enzyme-like size selection or shape stabilization of transition states can dramatically influence reaction pathways (transition state selectivity). (3) Finally, products can be selectively retained that are too large to be removed via the nano-vessel openings/pores (product selectivity). 

The intrazeolite cations necessary to balance the negative charge on the framework aluminum atoms are poorly shielded and as a result high electric (electrostatic) fields on the order of 1-10 V/nm are found in their vicinity. The magnitudes of the electric fields can be calculated from measured effects on the vibrational frequencies or intensities of IR bands of small diatomics such as CO or N2.24 They can also be determined from difference electron density maps determined by X-ray diffraction methods.25 These high electric fields can dramatically influence the stabilities of transition states with significant charge separations. 

Aromaticity is one of the fundamental principles of organic chemistry, used to predict products from chemical reactions based on the stability of the possible products, as well as to rationalize the stability of transition states, such as the transition state of the Diels Alder reaction (/). Aromatic species have An + 2n electrons in a cyclic system that allows complete delocalization of the electrons. 

Several review articles have been published on the catalytic functions of micelles and related systems (Fendler and Fendler, 1970, 1975 Menger, 1977 Berezin et al., 1973 Cordes and Dunlap, 1969 Cordes and Gitler, 1973 Kunitake, 1977 Kunitake and Okahata, 1976 Bunton, 1979). The conventional catalytic functions of micelles are, in most cases, related to (i) the concentration of reactants and catalytic acid-base species in the micellar phase due to electrostatic and/or hydrophobic forces and (it) the stabilization of transition states and/or destabilization of initial states by the micellar environments. The situation is more complex when one of the reagents is hydrophilic (Bunton et al., 1979). However, the last few years have witnessed several novel advances in this field especially in relation to enzymatic catalysis. 

In previous sections we have shown clearly that intramolecular dihydrogen bonds X-H- H-Y, with X and Y representing various chemical elements, can exist in both the solid state and in solution. In addition, the bonds can be a critical factor in the control of molecular conformational states or effects on rapid and reversible hydride-proton exchanges related to the process shown in Scheme 5.1, or the well-known H-D isotope exchanges in similar subsystems [23]. Such bonds could also play an important role in the stabilization of transition states, appearing as a reaction coordinate in many transformations. This is particularly... 

Stabilization of transition states by intramolecular dihydrogen bonding explains the high degree of fluxionality of polyhydride transition metal complexes. 

A third reason is that a sufficient length of polypeptide is needed to enforce the shape of a protein, and particularly the precise stereoelectronic architecture of its active site. In enzymes, for example, this allows coupled vibrations and energized motions that contribute to catalytic mechanisms and an exquisitely fine-tuned stabilization of transition states (Kraut, 1988 Havsteen, 1989 Retey, 1990 Knowles, 1991 Tonge and Carey, 1992 Williams, 1993). 

Density functional theory computational studies have been used to determine die importance of secondary orbital interactions for the stability of transition-state structures for die 4 + 2-cycloaddition of furan with cyclopropene.175 Kinetic studies of die 2 + 4-cycloaddition of 2-cyclopropylidene acetates with furan and dimethylful-vene suggest a mechanism involving diradicals or zwitterions as intermediates.176 Cyclopropene, produced by die reaction of allyl chloride with sodium bis(bimediyl-silyl)amide, reacts with 1,3-diphenylisobenzofuran to produce both endo- and exo-Diels-Alder cycloadducts isolated for the first tune.177... 

The range of catalytic proficiencies for enzymes suggests that there are features of catalysis in enzymes that involve factors other than stabilization of transition states. One important distinction is that the enzyme active site contains catalytic groups that are able to access reactive intermediates, while intermediates formed in solution have lifetimes that are less than the time needed for a reagent to diffuse to the site of the reaction.33 In the enzyme, groups are initially associated with the bound substrate in a specific array and continue to be available through the course of the reaction. Diffusional introduction of catalytic groups is overcome by pre-association of the catalysts and reactant prior to the formation of any reactive intermediate. This accesses modes of catalysis that are not possible if the catalyst and intermediate must become associated after the intermediate has formed. 

The Stabilization of Transition States by Cyclodextrins and other Catalysts... 

Essentially the only mechanism for the electronic stabilization of transition states is the bonding interaction between fully occupied and empty frontier orbitals. 

There have been a few reports of first generation coordination complex structural models for the phosphatase enzyme active sites (81,82), whereas there are some examples of ester hydrolysis reactions involving dinuclear metal complexes (83-85). Kim and Wycoff (74) as well as Beese and Steitz (80) have both published somewhat detailed discussions of two-metal ion mechanisms, in connection with enzymes involved in phosphate ester hydrolysis. Compared to fairly simple chemical model systems, the protein active site mechanistic situation is rather more complex, because side-chain residues near the active site are undoubtedly involved in the catalysis, i.e, via acid-base or hydrogenbonding interactions that either facilitate substrate binding, hydroxide nucleophilic attack, or stabilization of transition state(s). Nevertheless, a simple and very likely role of the Lewis-acidic metal ion center is to... 

In addition to carbenes exerting a strong trans influence (thermodynamic), which may be manifest as a trans effect (kinetic) in ligand substitution reactions, heteroatom-functionalized carbene ligands (with their associated dipolar resonance contributor, Figure 1.16) may assist in the stabilization of transition states of reduced coordination number by electron donation to the metal. 

As far as the tertiary benzylic solvolyses are concerned, any structural and mechanistic perturbations are reflected only in the variation of the p parameter. The p value for a reaction series is a parameter of intermolecular selectivity and can change sensitively with the reactivity (or the stability of transition state). This behaviour is often referred to as adherence to the reactivity-selectivity relationship (RSR), where the selectivity (5) may vary inversely with the intrinsic reactivity of members of a reaction series, as formulated in equation (3),... 

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