Tight transition state

Of course, the converse situation, in which the entropy of the transition state is lower than that of the ground state of the reactant, can also occur (Fig. 3.11). In this case, one speaks of a tight transition state tight, because rotations, vibration or motion of the activated complex are more restricted than in the ground state of the reactant. The dissociation of molecules on a surface provides an example that we shall discuss in the next section. 

The static pictures seen in crystal structures and ordered into a continuous series may therefore be interpreted as a model of the reaction path of an 8 2 or associative ligand interchange reaction. From the above discussion, it remains an open question whether the five-coordinate species would be an intermediate or transition state if such a reaction occurred in solution. However, the numerical value of the constant a characterizes the transition state tight if it is small and loose if it is large. 

The prediction that enzymes must bind their transition states tightly indicates that compounds, which are structurally similar to the transition state, may also bind tightly. Such transition state analogs have been synthesized for a number of specific enzymic reactions. It is generally found that they do, in fact, bind to their respective target enzymes much more strongly than do the substrates. This... 

Variational RRKM calculations, as described above, show that a imimolecular dissociation reaction may have two variational transition states [32, 31, 34, 31 and 36], i.e. one that is a tight vibrator type and another that is a loose rotator type. Wliether a particular reaction has both of these variational transition states, at a particular energy, depends on the properties of the reaction s potential energy surface [33, 34 and 31]- For many dissociation reactions there is only one variational transition state, which smoothly changes from a loose rotator type to a tight vibrator type as the energy is increased [26],... 

Mutations in the specificity pocket of trypsin, designed to change the substrate preference of the enzyme, also have drastic effects on the catalytic rate. These mutants demonstrate that the substrate specificity of an enzyme and its catalytic rate enhancement are tightly linked to each other because both are affected by the difference in binding strength between the transition state of the substrate and its normal state. 

There are important consequences for this statement. The enzyme must stabilize the transition-state complex, EX, more than it stabilizes the substrate complex, ES. Put another way, enzymes are designed by nature to bind the transition-state structure more tightly than the substrate (or the product). The dissociation constant for the enzyme-substrate complex is... 

Transition-State Analogs Bind Very Tightly to the Aetive Site... 

It is unlikely that such tight binding in an enzyme transition state will ever be measured experimentally, however, because the transition state itself is a... 

It should be noted that transition-state analogs are only approximations of the transition state itself and will never bind as tightly as would be expected for the true transition state. These analogs are, after all, stable molecules and cannot be expected to resemble a true transition state too closely. 

Compare the bonding surface in the transition state to those of the reactant and the products. The CO single bond of the reactant is clearly broken in the transition state. Also, the migrating hydrogen seems more tightly bound to oxygen (as in the product) than to carbon (as in the reactant). It can be concluded that the transition state more closely resembles the products than the reactants, and this provides an example of what chemists call a late or product-like transition state. 

The rate acceleration achieved by enzymes is due to several factors. Particularly important is the ability of the enzyme to stabilize and thus lower the energy of the transition state(s). That is, it s not the ability of the enzyme to bind the substrate that matters but rather its ability to bind and thereby stabilize the transition state. Often, in fact, the enzyme binds the transition structure as much as 1012 times more tightly than it binds the substrate or products. As a result, the transition state is substantially lowered in energy. An energy diagram for an enzyme-catalyzed process might look like that in Figure 26.8. 

When Sn2 reactions are carried out on these substrates, rates are greatly increased for certain nucleophiles (e.g., halide or halide-like ions), but decreased or essentially unaffected by others. For example, a-Chloroaceto-phenone (PhCOCH2Cl) reacts with KI in acetone at 75°C 32,000 times faster than l-Chlorobutane, ° but a-bromoacetophenone reacts with the nucleophile triethylamine 0.14 times as fast as iodomethane. The reasons for this varying behavior are not clear, but those nucleophiles that form a tight transition state (one in which bond making and bond breaking have proceeded to about the same extent) are more likely to accelerate the reac-tion. ... 

Strictly speaking, the conformations and relative geometries of the reactants must be known over the entire reaction coordinate moreover, there are indications that the transition states in enzyme reactions, which often have very different preferred conformations from those of the bound substrates, may be more tightly bound to the enzyme than either the starting materials or the products (1). 

CO2 channel dominates as it is spin allowed and occurs via a loose transition state. In contrast, production of VO is spin forbidden and goes via a tight transition state that lies higher in energy than W" + CO2. 

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