Phosphoryl transfer catalysis

For a detailed review of the work on phosphoryl transfer catalysis by macrocyclic polyamines see M. W. Hosseini, Bioorg. Chem. Frontiers 1993,3, 67. 

Catalysis can be broken down into a number of areas, depending on the substrate and the catalytic reaction. One of the prime areas of the initial effort in catalysis has been small molecule activation, such as oxygen with a number of transition metal ion macrocycles and carbon dioxide, the latter particularly with cobalt(I) and nickel(I) macrocycles. Once the polyanunonium macrocycles were found to be able to recognize substrates other than metal ions, other catalysis applications evolved. For example, phosphoryl transfer catalysis with simple polyanunonium macrocycles has become quite accessible. ... 

Papoyan. G. Gu, K. Wibrkiewicz-Kuczera. J. Kuczera. K. Bowman-James. K. Molecular dynamics simulations of nitrate complexes with polyammonium macrocycles Insight on phosphoryl transfer catalysis. J. Am. Chem. Soc. 1996. 118. 1354- 1364. 

Phosphorylation of phenolate anions with dimethyl phosphorochloridothionate in water-dichloromethane systems normally gives large amounts of dithiopyrophos-phate because of extensive hydrolysis of the phosphorus chloride, but in the presence of tetrabutylammonium salts and 1 % imidazole, phosphorylation of the phenolate anion is complete. The explanation lies in an evident combination of activation of acylating agent (by imidazole) and of nucleophile (by phase-transfer catalysis).71... 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

Oxygen-based nucleophiles can also be employed for the catalysis of acyl transfer. For example, pyridine-A-oxide derivatives such as 4-DMAP-A-oxide have long been known as such catalysts although, interestingly, these catalophores are reportedly particularly efficient at mediating sulfonyl and phosphoryl transfer [229-230]. 

This phosphotransferase [EC 2.7.2.1] catalyzes the thermodynamically favored phosphorylation of ADP to form ATP Aeq = [ATP][acetate]/ [acetyl phosphate] [ADP] = 3000). GDP is also an effective phosphoryl group acceptor. This enzyme is easily cold-denatured, and one must use glycerol to maintain full catalytic activity. Initial kinetic evidence, as well as borohydride reduction experiments, suggested the formation of an enzyme-bound acyl-phosphate intermediate, but later kinetic and stereochemicaT data indicate that the kinetic mechanism is sequential and that there is direct in-line phosphoryl transfer. Incidental generation of a metaphosphate anion during catalysis may explain the formation of an enzyme-bound acyl-phosphate. Acetate kinase is ideally suited for the regeneration of ATP or GTP from ADP or GDP, respectively. 

In both schemes, the specificities of the pump for catalysis change in the two enzyme states. Jencks points out that coupling is determined (a) by the chemical specificity achieved in catalyzing phosphoryl transfer to and from the enzyme (wherein E-Ca2 reversibly binds ATP, and E reacts reversibly with orthophosphate), and (b) by the vectorial specificity for ion binding and dissociation (wherein E reversibly binds/dissociates cytoplasmic calcium ion, and E—P reversibly binds/dissociates luminal calcium). There must be a single conformation change during the reaction cycle between Ei and E2 in the free enzyme and from Ei P-Ca2 to E2-P-Ca2 after enzyme phosphorylation. 

Both ATP and the phosphoryl acceptor become reversibly and selectively bound to the enzyme during catalysis. So far, kinases that have been shown to react by direct phosphoryl transfer between ATP and the co-substrates show strict inversion of configuration at phosphorus, while those with a phosphorylated enzyme Intermediate show retention of configuration at phosphorus (1,2). 

The development of anion coordination chemistry and anion receptor molecules has opened up the possibility to perform molecular catalysis on anionic substrates of chemical and biochemical interest, such as adenosine triphosphate. The catalysis of phosphoryl transfer is of particular interest, namely in view of the crucial role of such processes in biology and of the numerous enzymes that catalyse them. 

Multiple recognition and catalysis in ATP hydrolysis with increased ATP/ADP selectivity has been achieved with a multifunctional anion receptor containing a macrocyclic polyamine as anion binding site, an acridine group as stacking site and a catalytic site for hydrolysis (structure 82) [4.27]. Phosphoryl transfer is accelerated by other types of hydrogen-bonding receptors [5.24a]. 

Suelter90 has classified enzymes that are activated by monovalent cations into two groups. One involves the catalysis of phosphoryl-transfer reactions and the other a variety of elimination and/or hydrolytic reactions in which a keto-enol tautomer can be invoked as an intermediate. The M+ cation is then required to stabilize the enolate anion. It is still not possible to verify this hypothesis, but it seems unlikely in view of the comments above. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

DNA polymerases catalyze DNA synthesis in a template-directed manner (Box 16). For most known DNA polymerases a short DNA strand hybridized to the template strand is required to serve as a primer for initiation of DNA synthesis. Nascent DNA synthesis is promoted by DNA polymerases by catalysis of nucleophilic attack of the 3 -hydroxyl group of the 3 -terminal nucleotide of the primer strand on the a-phosphate of an incoming nucleoside triphosphate (dNTP), leading to substitution of pyrophosphate. This phosphoryl transfer step is promoted by two magnesium ions that stabilize a pentacoordinated transition state by complex-ation of the phosphate groups and essential carboxylate moieties in the active site (Figure 4.1.1) [2],... 

In the above aminolysis reactions, Mg2+ ion always activates P—O fission. Other divalent metal ions behave similarly. Change of nucleophile might result in the change of P—O to S—O fission. To pursue the possibility of metal ion catalyzed S—O fission under neutral conditions, we examined the catalysis of the Zn2+-pyridine-2-carboxaldoxime (Zn2+PCA) complex, since catalytic activity of this complex has been well known in some acyl and phosphoryl transfer reactions (18, 19, 20). However, the results described below again indicate that the complex promotes an exclusive P-O bond fission (21). 

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