Phosphorus pentacovalent intermediate

The various proposals have each evolved with time, and the issues are numerous and intertwined. There is general agreement that the phosphorus is attacked by an oxygen atom made more nucleophilic catalyti-cally. A catalytically stabilized pentacovalent intermediate (or activated state) is accepted. Specific catalytic protonation of the leaving group is involved. There is also agreement that at least two of the three residues His 12, His 119, and Lys 41 are involved crucially in the mechanism. 

Now the alkoxide anion can attack the positively charged phosphorus atom. This is a good reaction in two ways. First, there is the obvious neutralization of charge and, second, the P-O bond is very strong. This reaction, which we have drawn as an S>j2 reaction at phosphorus, really goes through a pentacovalent intermediate shown to the right, but you will usually see it drawn in a concerted fashion. r -i... 

The actual substrates are Mg2+ complexes of ADP and ATP, as in all knovm phosphoryl transfer reactions with these nucleotides. A terminal oxygen atom of ADP attacks the phosphorus atom of P to form a pentacovalent intermediate, which then dissociates into ATP and H2O (Figure 18.28). The attacking oxygen atom of ADP and the departing oxygen atom of P occupy the apices of a trigonal bipyramid. 

Figure 18.28. ATP Synthesis Mechanism. One of the oxygen atoms of ADP attacks the phosphorus atom of Pj to form a pentacovalent intermediate, which then forms ATP and releases a molecule of H2O.

Organic halides of other elements [tin (43-45), phosphorus (6,54), nitrogen (46,93,245,251), sulfur (232,233,252,256-259)1 also participateV in Michaelis-Arbuzov type reactions. Heating the organic lead compound EtsPbBr with (EtO)3P at 100° gave only an unidentified white amorphous solid (45). Petrov and SokoPskii (250), who observed the formation of phosphate esters from the reactions of ethyl hypochlorite with various phosphite esters, proposed the existence of a pentacovalent intermediate which decomposed by loss of alkyl halide. 

The mechanism has been viewed as involving either the formation of a pentacovalent phosphorus intermediate,14,15 or alternatively, by initial... 

This initial hypothesis was subsequently refined by the deduction of two preference rules for the structures of the intermediate pentacovalent phosphorus derivatives, the phosphoranes. Muetterties and Schunn65. in order to rationalize the nmr spectra of a number of alkyl fluorophosphoranes (CH3) -PF5 . formulated the hypothesis that the more electronegative fluorine atoms... 

It is well known that pentacovalent cyclic phosphorus compounds play an important role as intermediates in reactions involving nucleophilic attack on tetracoordinated phosphorus in biological systems. According to this background it appears to us that it is important to prepare the arsenic derivatives, which are more stable than the corresponding phosphorus compounds and allow the study of their conformation. 

The alkali removes a proton from the 2 -OH group, which cyclizes on to the phosphate link— possible only if the ring fusion is cis. The next reaction involves breakdown of the pentacovalent phosphorus intermediate to give a cyclic phosphate. One nucleoside is released by this reaction and the second follows when the cyclic phosphate is itself cleaved by alkali. 

Lahiri SD, Zhang GF, Dunaway-Mariano D et al (2003) The pentacovalent phosphorus intermediate of a phosphoryl transfer reaction. Science 299 2067-2071... 

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