TS analysis results and recent developments

Understanding catalytic mechanisms and designing inhibitors requires an understanding of the structure and charge distribution of the oxocarbenium ion. The resonance structures of an oxocarbenium ion imply a molecule that is somewhere between a carbocation (la) and an oxonium ion (lb). 

Information on the nature of the oxocarbenium ion from a variety of experimental and computational approaches has indicated that the oxonium-like resonance form lb predominates.Evidence emerging from TS analysis supports this model. In TS structures derived from both ad hoc and structure interpolation techniques, and supported by electronic structure calculations, essentially all the loss in bond order upon leaving group departure is compensated by increases in the Cff-04 and Cff-C2 bond orders. In NAD hydrolysis reactions, the total bond 

Atom Charge [ (e )] Bond Pauling bond order  

The computational results are supported by four lines of experimental evidence. 

Further evidence comes from a model of the DTA-TS complex for NAD hydrolysis based on the X-ray crystal structure of DTA-NAD. In the complex, the positive charge that would accumulate on the anomeric carbon at the transition state was located directly adjacent to the carboxylate of a glutamate residue that is completely conserved in the bacterial toxin sequences. 

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The meaning of KIEs in enzymatic reactions 247 The reaction coordinate and the structure of the transition state 249 Very low bond orders 250 Observable KIEs for stepwise reactions 250 Erom experimental KIEs to transition states 251 TS analysis results and recent developments 255 The nature of the oxocarbenium ion 255 Non-chemical steps 259 Transition state imbalance 261 Secondary KIEs 266 Catalytic strategies 273 Specific reactions 283... 

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