P—O ester bonds

In the author s own laboratory the Cu(II)-catalyzed hydrolysis of the phosphate ester derived from 2-[4(5)-imidazolyl] phenol recently has been investigated146. The pertinent results are (a) the pre-equilibrium formation of a hydrolytically labile Cu(II)-substrate complex (1 1), (b) the occurrence of catalysis with the free-base form of the imidazolyl and phosphate moieties and (c) the extraordinary rate acceleration at pH 6 (104) relative to the uncatalyzed hydrolysis146. The latter recalls the unusual rate enhancement encountered above with five-membered cyclic phosphates and suggests a mechanism in which the metal ion, at the center of a square planar complex or a distorted tetrahedral complex, might induce strain in the P-O ester bonds (60). viz. 

Ribonucleases are a widely distributed family of en-zymes that hydrolyze RNA by cutting the P—O ester bond attached to a ribose 5 carbon (fig. 8.12). A good representative of the family is the pancreatic enzyme ribonuclease A (RNase A), which is specific for a pyrimidine base (uracil or cytosine) on the 3 side of the phosphate bond that is cleaved. When the amino acid sequence of bovine RNase A was determined in 1960 by Stanford Moore and William Stein, it was the first enzyme and only the second protein to be sequenced. RNase A thus played an important role in the development of ideas about enzymatic catalysis. It was one of the first enzymes to have its three-dimensional structure elucidated by x-ray diffraction and was also the first to be synthesized completely from its amino acids. The synthetic protein proved to be enzymatically indistinguishable from the native enzyme. 

As described in Chapters 1 and 8, P-NMR chemical shifts in nucleic acids have been shown to provide a direct probe of P—O ester bond torsional angles. The interaction of drugs with nucleic acids is believed to perturb the conformation of the sugar-phosphate backbone, and hence structural and dynamic information on these complexes is potentially readily accessible through 3 P-NMR spectroscopy. 

The insertion of the oxiranes into a P-O-C- bond of the mixed ester takes place in the reaction of the O-alkyl O-silyl phosphonates 3 with oxiranes in contrast to the reaction above. The formed 0-(2-siloxyethyl) O-alkyl phosphonates 11 show the typical PH-reactivity with the protected HO-group for further reactions. 

Quite recently it was shown that phosphonic esters, trimethylsilyl [124, 143] and alkyl esters [124,143, 145] could also be used to modify the surface of titanium or aluminum oxide in organic solvents at moderate temperatures. Unlike Si-O-C bonds, P-O-C bonds are not easily hydrolyzed, and their cleavage on an oxide surface was unexpected. Most probably, coordination of the phosphoryl oxygen to the surface assists the condensation by increasing the electrophilicity of the P atom, thus facilitating the condensation of P-0-R groups with surface hydroxyls (Scheme 7) [124]. The chemisorption of... 

Ground state /-effects of silicon may be responsible for the elongated C(alkyl)-O(ester) bond in n.s-3-trimelhylsilylcyclohexyl p-nitrobenzoate 59 relative to the silicon-free derivative. It is suggested that the ground state /-effect could be due either to homohyperconjugation, 60, or to inductively enhanced C—C hyperconjugation where the trimethylsilyl substituent increases the importance of the resonance form 61 relative to the silicon-free derivative. 

It is shown that the five major structure features predominating the extraction ability of uranium are number of P-C bonds (+) AD(-) number of -CH2- (non-ester) (+) number of P-O-C bonds (-) WD (-). In the parenthese the tendency of the feature which is necessary for compounds of higher reactivity is given. 

Fig. 8 Potential mechanisms for hydrolysis of phosphomonoester monoanions. In mechanism (a), proton transfer from the phosphoryl group to the ester oxygen (probably via the intermediacy of a water molecule) yields an anionic zwitterion intermediate. This may react in either concerted fashion (upper pathway) or via a discrete metaphosphate intermediate in a preassociative mechanism (bottom pathway). Mechanism (b) denotes proton transfer concerted with P-O(R) bond fission. As with (a), such a mechanism could either occur with concerted phosphoryl transfer to the nucleophile (upper pathway) or via a discrete metaphosphate intermediate in a preassociative mechanism (bottom pathway).

The effect of packing forces and hydrogen bonds upon the observed puckered conformations of nucleosides in the solid state is well-known [56, 57]. [the anomeric effect across the 3 O-P-O-ester fragment in the sugar-phosphate backbone see references cited therein]. Solution and solid-state conformations of pentofuranose differ dramatically for some nucleosides adenosine [58] crystallizes as the N-type conformer, whereas its hydrochloride salt crystallizes as the S-type conformer [59]. 

Bingol et al ° have demonstrated, especially by means of electrospray ionization mass spectrometry (ESI-MS), that polymerization of vinylphos-phonates is mainly dominated by transfer reactions the predominant transfer occurs by intramolecular hydrogen transfer of phosphonate ester groups, which in consequence creates a P-O-C bond in the main chain (Scheme 3.2). Moreover P-O-C bonds are more thermally labile compared to phosphonate, and thus lead to chain scission reactions. 

The hydrolysis of an orthophosphate ester involves breaking P-O-C bonds at either P-0 or 0-C linkages, depending on the conditions anployed. In the case of condensed phosphate esters, the rupture of both P-O-C and P-O-P linkages may take place, althongh the latter usually occurs first. 

Phosphorus is absorbed by animals from food (and by plants from the soil (Chapter 12.2)) in the form of phosphate ions HPO and H2PO4. In animals some of the element is found in this form in blood, urine and tissue fluids, but mostly as inorganic calcium salts in bones and teeth. The remaining phosphorus is present as organic phosphate , which is almost all in the form of numerous mono-and di-esters in which fully oxidised P is almost always linked indirectly to carbon through P-O-C bonds. In a few compounds P-NH-P linkages are formed. 

P)—phenyl ester bond (p)—o-nitrobenzylester bond (p)—amino acid ester bond... 

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