Transition state structure, crystallographic

Tetrahedral intermediates, derived from carboxylic acids, spectroscopic detection and the investigation of their properties, 21, 37 Topochemical phenomena in solid-state chemistry, 15, 63 Transition state structure, crystallographic approaches to, 29, 87 Transition state structure, in solution, effective charge and, 27, 1 Transition state structure, secondary deuterium isotope effects and, 31, 143 Transition states, structure in solution, cross-interaction constants and, 27, 57 Transition states, the stabilization of by cyclodextrins and other catalysts, 29, 1 Transition states, theory revisited, 28, 139... 

Transition state analysis using multiple kinetic isotope effects, 37, 239 Transition state structure, crystallographic approaches to, 29, 87 Transition state structure, in solution, effective charge and, 27, 1 Transition stale structure, secondary deuterium isotope effects and,... 

X-ray crystallographic studies of serine protease complexes with transition-state analogs have shown how chymotrypsin stabilizes the tetrahedral oxyanion transition states (structures (c) and (g) in Figure 16.24) of the protease reaction. The amide nitrogens of Ser and Gly form an oxyanion hole in which the substrate carbonyl oxygen is hydrogen-bonded to the amide N-H groups. 

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... 

This chapter reviews crystallographic approaches to transition state structure. At first sight this appears to be a contradiction in terms crystal... 

Stable compounds which resemble the transition-state structure of a substrate in an enzymatic reaction are expected to behave as potent reversible inhibitors (1 ). Based on the X-ray crystallographic structure of the active site of carboxypeptidase A (CPA) (2), a mechanism was proposed in which a water molecule adds directly to the scissile carbonyl group of the substrate to give the tetrahedral intermediate 1, which collapses to products (3). We proposed to mimic this tetrahedral intermediate, similar to the transition state, with the stable tetrahedral phosphonic acid derivatives 2,... 

A variety of techniques have been applied to investigate enzyme reaction mechanisms. Kinetic and X-ray crystallographic studies have made major contributions to the elucidation of enzyme mechanisms. Valuable information has been gained from chanical, spectroscopic and biochemical studies of the transition-state structures and intermediates of enzyme catalysis. Computational studies provide necessary refinement toward our understanding of enzyme mechanisms. The ability of an enzyme to accelerate the rate of a chemical reaction derives from the complementarity of the enzyme s active site structure to the activated complex. The transition state by definition has a very short lifetime ( 10 s). Stabilization of the transition state alone is necessary but not sufficient to give catalysis, which requires differential binding of substrate and transition state. Thus a detailed enzyme reaction mechanism can be proposed only when kinetic, chemical and structural components have been studied. The online enzyme catalytic mechanism database is accessible at EzCatDB (http //mbs.cbrc.jp/EzCatDB/). 

Kirby, A. J. (1994). Crystallographic approaches to transition state structures. Advances in Physical Organic Chemistry, 29, 87-183. 

The X-ray structure of the dibromine complex with toluene (measured at 123 K) is more complicated, and shows multiple crystallographically independent donor/acceptor moieties [68]. Most important, however, is the fact that in all cases the acceptor shows an over-the-rim location that is similar to that in the benzene complex. In both systems, the acceptor is shifted by 1.4 A from the main symmetry axis, the shortest Br C distances of 3.1 A being significantly less than the sum of the van der Waals radii of 3.55 A [20]. Furthermore, the calculated hapticity in the benzene/Br2 complex (x] = 1.52) is midway between the over-atom (rj = 1.0) and over-bond (rj = 2.0) coordination. In the toluene complex, the latter varies from rj = 1.70 to 1.86 (in four non-equivalent coordination modes) and thus lies closer to the over-bond coordination model. Moreover, the over-bond bromine is remarkably shifted toward the ortho- and para-carbons that correspond to the positions of highest electron density (and lead to the transition states for electrophilic aromatic bromination [12]). Such an experimental location of bromine is in good agreement with the results of high level theoretical... 

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