Biological chemistry of phosphate esters cyclic substrates and transition states

Biological chemistry of phosphate esters cyclic substrates and transition states 

The mechanisms of phosphoryl-group transfer reactions have been elucidated through studies on nucleophilic substitution reactions at phosphorus. 

Although direct information has come from studies on phosphate esters, studies on other tetrahedral and pentacoordinate phosphorus species have been required to elucidate principles such as pseudorotation, apicophilicity and the trigonal bipyramidal transition state. Application of the guidelines for associative nucleophilic substitution at phosphorus, discussed in the previous section of this review, has led to a good understanding of many biological mechanisms involving substitution at phosphorus. 

As we have noted, studies on cyclic phosphorus species have provided the foundation for the development of these guidelines. It is therefore appropriate to discuss selected areas of the biological chemistry of phosphorus in which the inclusion of phosphorus in a small ring influences its chemistry and biochemistry. 

This situation was presaged by Westheimer (1980), who stated ... that all enzymic reactions at phosphorus proceed with inversion and therefore they occur without pseudorotation at phosphorus. The argument for such a statement is based on two tenets first, the molecular motion caused by pseudorotation may require a conformational change of the enzyme to accommodate this movement secondly, a pseudorotation pathway will require a multistep mechanism. For example, the cyclization step of the reaction catalysed by ribonuclease may be postulated to involve pseudo- 

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