Phosphate diester and triester

Phosphate monoester hydrolysis 133 Phosphate diester and triester hydrolysis 137 References 173... 

Several multinuclear zinc complexes that exhibit phosphate diester and triester reactivity have been reported. A binuclear analog of [(CR)Zn]2+ (Fig. 6a) in which two [(CR)Zn]2+ units are linked by an aromatic spacer was found to be 4.4 times more effective in terms of the hydrolysis of diphenyl 4-nitrophenyl phosphate in CH3CN H20 at 25 °C than its mononuclear analog.204... 

Table 4 Rates for hydrolysis of cyclic phosphate diesters and triesters relative to acyclic diesters and triesters.

The mechanisms of phosphate ester cleavage vary significantly between monoesters, diesters, and triesters (Thatcher and Kluger, 1989). Each of these is a target for antibody cleavage and progress has been reported for all three cases. 

Configurational assignment to cyclic [l80]phosphodiesters is made by alkylating the phosphate group to a mixture of axially and equatorially alkylated phosphate diesters. The triesters in Equation 9 exemplify the nature of the product mixture ... 

Cryptate complexes with macrobicychc hgands containing three bipy units, in which the Ln + ion is contained within a hgand cavity, have been synthesized. Such hgands will complex Ln + ions, such as Eu + and Sm +, under conditions where Ln + ions are not. An application has been using lanthanide cryptates of the early lanthanides (La, Ce, Eu) as catalysts in the hydrolysis of phosphate monoesters, diesters, and triesters. Schiff base complexes can be synthesized by the reaction of a lanthanide salt with a diamine and a suitable carbonyl derivative such as 2,6-diacetylpyridine. 

Phosphoryl transfer reactions have essential roles throughout biochemistry. The enzymes that catalyze these reactions result in tremendous rate enhancements for their normally unreactive substrates. This fact has led to great interest in the enzymatic mechanisms, and debate as to whether the mechanisms for enzyme-catalyzed hydrolysis of phosphate esters differ from those of uncatalyzed reactions. This review summarizes the uncatalyzed reactions of monoesters, diesters and triesters. A selection of enzymatic phosphoryl transfer reactions that have been the most studied and are the best understood are discussed, with examples of phosphatases, diesterases, and triesterases. 

Fig. 1 From left to right, the structures of a phosphate monoester, diester, and triester. Depending upon pH, monoesters may be neutral, monoanionic, or dianionic diesters may be neutral or anionic. The first pKa of an alkyl phosphomonoester, and the pKa of a dialkyl diester, is 2. The second pKa of an alkyl monoester is 6.8. Oxygen atoms bonded to ester groups (OR) are called bridging oxygen atoms the other oxygen atoms are nonbridging. Thus, a triester has one nonbridging oxygen atom, an ionized diester has two, and a fully ionized monoester has three.

These workers point to the discrepancy between the observed difference in activation enthalpy AAH = 4.5 kcal mor ) and the difference in free energy of hydrolysis AAG = 10.5 kcal mol ). A possible explanation is proffered in terms of solvation effects amplified in the transition state for hydrolysis. Solvation effects are expected to be far more important for phosphate diesters than triesters. Therefore it cannot be assumed that these relative values are directly transferable to the hydrolysis of acyclic and cyclic triesters such as MEP. 

The principal phosphation reagents used to manufacture phosphate esters are phosphoric anhydride (P4O10), phosphorus oxychloride [P(0)Cl3], and polyphosphoric acid. It is important to understand the physical and chemical characteristics of each raw material. The structure of the phosphation agent affects its reactivity and selectivity, resulting in variation in the monoester, diester, and triester product distribution. 

Some of the concepts most attractive for the simplification of oligonucleotide synthesis and, thus, also for reducing cost and effort of potential large-scale preparations, come from a combination of two of the three operations essential for conventional chain-elongation. Although the combination of protection and activation principles plays a minor role in phosphate-diester and phosphate-triester chemistry, this is the basis of success of the phosphoramidite synthesis (23,24). The relative stability of nucleoside phosphoramidites at room temperature and their fast and efficient activation by tetrazole (23) (see also 25 for mechanistic studies) are essential to today s most utilized process of internucleotide bond formation. 

Dephosphorylation reactions of 2,4-dinitrophenyl phosphate with benzohydroxamate and deferoxamine (DFO) (130) occur by attack at phosphorus, but because they involve attacks by monoanions on dianions, they are only modestly accelerated by these a-nucleophiles. This is in contrast to their extraordinary reactivity towards the di- and triesters of 2,4-dinitrophenyl phosphate (described in the section titled Phosphate and Phosphonate Diester and Triesters ). 

The phosphorylation of imidazole by two activated phosphate diesters and a triester gave phosphorylimidazole derivatives (62-66), that were stable enough in aqueous solution, and were observed and identified by ESI-MS/MS and NMR. Half-lives ranging from hours to days (in the case of the monoethyl ester) showed that it was possible to design molecules with variable half-lives with a potential to be used for biological intervention experiments as possible inhibitors of biosignaling processes or as haptens for the generation of antibodies. ... 

Reactions of monoester dianions were found to be significantly accelerated by the addition of DMSO, whereas reactions of diesters and triesters show much less rate enhancement. The rate of hydrolysis of bis(p-nitrophenyl) phosphate (BNPP), a phosphate diester, sHghtly decreased at intermediate DMSO content (0—60%), and then increased, with an overall... 

Catrina IE, Hengge AC. Comparisons of phosphorothioate with phosphate transfer reactions for a monoester, diester, and triester isotope effect studies. J Am Chem Soc. 2003 125 7546-7552. 

A gel of diesel or crude oil can be produced using a phosphate diester or an aluminum compound with phosphate diester [740]. The metal phosphate diester may be prepared by reacting a triester with phosphorous pentoxide to produce a polyphosphate, which is then reacted with an alcohol (usually hexanol) to produce a phosphate diester [870]. The latter diester is then added to the organic liquid along with a nonaqueous source of aluminum, such as aluminum isopropoxide (aluminum-triisopropylate) in diesel oil, to produce the metal phosphate diester. The conditions in the previous reaction steps are controlled to provide a gel with good viscosity versus temperature and time characteristics. All the reagents are substantially free of water and will not affect the pH. 

The use of a lipophilic zinc(II) macrocycle complex, 1-hexadecyl-1,4,7,10-tetraazacyclododecane, to catalyze hydrolysis of lipophilic esters, both phosphate and carboxy (425), links this Section to the previous Section. Here, and in studies of the catalysis of hydrolysis of 4-nitrophenyl acetate by the Zn2+ and Co2+ complexes of tris(4,5-di-n-propyl-2 -imidazolyl)phosphine (426) and of a phosphate triester, a phos-phonate diester, and O-isopropyl methylfluorophosphonate (Sarin) by [Cu(A(A(A/,-trimethyl-A/,-tetradecylethylenediamine)l (427), various micellar effects have been brought into play. Catalysis of carboxylic ester hydrolysis is more effectively catalyzed by A"-methylimidazole-functionalized gold nanoparticles than by micellar catalysis (428). Other reports on mechanisms of metal-assisted carboxy ester hydrolyses deal with copper(II) (429), zinc(II) (430,431), and palladium(II) (432). 

Diester methods have been used to synthesize analogues of the initiator codon ApUpG in which the adenine residue has a fixed torsion angle, as for instance in (78),132 and triester methods have been used to prepare dinucleoside phosphates and codon analogues133 134 containing the hydroxyalkyl nucleosides 9-(4 -hydroxybutyl)-adenine (80), 9-(3 -hydroxypropyl)adenine (81), and 1 -(3 -hydroxypropyl)uracil (82), with a view to determining the effect of the achiral residues on the c.d. spectra. 

Phosphate Esters. An ester is formed by elimination of H20 and formation of a linkage between an acid and an alcohol (or phenol) (Fig. III-22). Phosphomonoesters, especially of monosaccharides, are very common (Fig. ffl-23). Because phosphoric acid is a tribasic acid, it can also form di- and triesters (Fig. III-24). Phosphotriesters are rarely found in nature, but diesters are extremely important, particularly as the fundamental linkage of the nucleic acid polymers, which are sequences of ri-bose (or deoxyribose) units linked by 3 —> 5 phos-phodiester bonds (see Fig. III-25). Like phosphoric acid, which has three dissociable protons (Fig. III-26), phosphomono- and phosphodiesters are acidic and typically ionize as shown in Fig. HI-27. Note the similarities between the pvalues for... 

In the case of phosphates, the triesters are most susceptible to nucleophilic attack and hence the base-catalyzed reaction generally predominates in the pH-rate profile of these esters. Phosphate diesters, with the exception of small ring cyclic ones, are relatively unreactive in neutral... 

A mild and efficient deprotection of phosphate triesters involves nucleophilic attack by weakly basic nucleophiles such as iodide, thiolate and amines at the O-C bond with synchronous expulsion of a phosphate diester as the leaving group [Scheme 7.6]. The reaction is especially useful for the deprotection of methyl, benzyl and allyl phosphates as in Scheme 7.8 shown below. An analogous reaction occurs with carboxylic esters but the conditions required are more stringent because the carboxylate anion is a poorer leaving group (see section 6.3.1),... 

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