Propinquity catalysis effect

Amide hydrolysis is not only subject to acid and base catalysis, but may be also brought about by a neighbouring group in the amide, the so-called propinquity catalysis effect. Wolfrom et a/.238 were among the first to suggest this possibility, in order to explain the observed hydrolysis of aldonamides, viz. 

Catalysis occurs because the catalyst in some manner increases the probability of reaction. This may result from the reactants being brought closer together [catalysis by approximation, or the propinquity effect ], or somehow assisted to achieve the necessary relative orientation for reaction. Noncovalent interactions may be responsible for the effect. Covalent bond changes may also take place in catalysis. In a formal way, the manner in which catalysis occurs can be described by schemes such as Schemes I and II. 

Koshland (1962) has calculated, however, that such a propinquity effect will not explain the large rate enhancements observed with enzymes unless there are more than two functional groups involved with utilization of five functional groups (2 substrates and 3 catalytic groups) a rate increase of 10 would be possible. Such multifunctional catalysis would, of course, be impossible to demonstrate... 

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