Hexacoordinate phosphorus via donor interaction. Implications regarding enzymatic reaction intermediates

A new aspect of active site interactions of phosphoryl tranfer enzymes undergoing nucleophilic attack is suggested by structural studies on phosphites, phosphates, and oxyphosphoranes which are shown to interact with donor groups to give higher coordinate geometries. The degree of coordination increases from phosphate to pentaoxyphosphoranes which model substrates and active site transition states, respectively. Thus, a rate enhancement effect is anticipated due to stronger enzyme binding in the transition state - enzyme complex if this effect is present. It is shown that the donor groups, oxygen, sulfur, and nitrogen, typical of enzyme residues at active sites of phosphoryl transfer enzymes, cause higher coordination. Specifically, tetracoordinate phosphate substrates are displaced modestly toward trigonal bipyramid geometries by donor coordination while five-coordinate pentaoxyphosphoranes are displaced more strongly toward octahedral geometries by donor action. The studies suggest that donor interactions at applicable active sites may assist in nucleophilic attack in causing a more ready cleavage of P - O bonds undergoing displacement to form products.