Direct observation of simple tetrahedral intermediates

Abstract

the stability of the OHat the active site is increased even more by long-range hydrogen-bonding interactions between the active (nucleophilic) H20 and components of what has been termed the "water chain" in the active site, indicating again the importance of residues around but not in the active site.Quantum and molecular mechanical calculations have thus provided insights into rate-enhancing factors in enzyme catalysis. Long-range electrostatic and hydrogen-bonding effects are crucial. It will be of interest to investigate these in a systematic manner to discover where the major portion of electrostatic stabilization energy in charge separation processes is centered. It will be further desirable to develop methods to calculate

On the antiperiplanar lone pair hypothesis and its application to catalysis by glycosidases

“…There are a number of experimental difficulties with ALPH; results with cyclic orthoesters were originally rationalized on the assumption that the lifetime of a hemiorthoester was short compared with the time of rotation about C-0 bonds. With the direct detection of such intermediates (Capon et al, 1981;McClelland & Santry, 1983) this assumption has become untenable; moreover, some of the original experiments were shown to be wrong (Capon & Grieve, 1982). Nonetheless, it has proved possible to rationalize the correct experimental data (on mild acid hydrolysis, conformationally labile cyclic orthoesters such as I give a mixture of lactone and hydroxyester but conformationally rigid ones such as II give hydroxyester exclusively) by invoking a 'secondary stereoelectronic effect' as well as a primary one (Deslongchamps, 1983, pp.…”

Intramolecular Reversible Addition Reactions to the C=O Group

“…Following an intramolecular nucleophilic addition of the X-H group (X = 0, N R, S) to the acyl C=O group the cyclic tetrahedral intermediate (203) depending on the pH value of the medium opens along the most easily polarizable bond (C-X or C-Y). Cyclic intermediates (203) rarely are isolated because they are of low stability [624].…”

“…It does not matter if centers X and Y differ greatly in nucleophilicity as indicated by arylthiotropones (211, X = 0, Y = S, R 1 = R2 = H) where the equilibrium is totally displaced toward (213). It is not within the scope of this book to discuss in detail intramolecular migrations of acyl and similar groups (see reviews [618][619][620][621][622][623][624]). We only want to show that structural factors, governing intramolecular additions of XH groups to C=O bonds in ring-chain tautomeric systems, also rule intramolecular acyl migrations and similar reactions which proceed via cyclic tetrahedral intermediates.…”

Hydrolysis and retro‐aldol cleavage of ethyl threo‐2‐(1‐adamantyl)‐3‐hydroxybutyrate: competing reactions

“…The hydrolysis of carboxylic acid esters (RCOOR') is one of the most fundamental and thoroughly studied chemical reactions 1–9. A variety of experimental and theoretical studies10–55 on ester hydrolysis have provided critical insights into the fundamental reaction mechanism. Besides extensive interests within chemistry, the mechanism of base‐catalyzed hydrolysis of esters figures prominently in many biological processes,6–9, 56, 57 such as the metabolism of the neurotransmitter acetylcholine and the degradation of cocaine.…”