1207. Hydrolysis of hydroxyalkyl phosphate esters: effect of changing ester group

Brown, D. M.; Usher, D. A.

doi:10.1039/jr9650006558

Cited by 157 publications

(141 citation statements)

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“…Compounds tris[2-(1-methylbenzimidazole-2-yl)ethyl]nitromethane I and tris[2-(1-methylbenzimidazole-2-yl)-ethyl]-methylamine II have been synthesized by the previously described method [40]. The barium(II) salt of the phosphate diester HPNP was synthesized by literature methods [41]. Nitrilotriacetic acid (NTA) and N-methyl-O-phenylenediamine were purchased from Sigma.…”

Section: Methodsmentioning

confidence: 99%

A Novel Dinucleating Ligand-Containing Hexabenzimidazoles and Its Dinuclear Zinc Complex Bridged by a Carboxylate Group for the Hydrolysis of 2-Hydroxypropyl-p-nitrophenyl phosphate

Ibrahim

2009

J Inorg Organomet Polym

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Section: Methodsmentioning

confidence: 99%

A Novel Dinucleating Ligand-Containing Hexabenzimidazoles and Its Dinuclear Zinc Complex Bridged by a Carboxylate Group for the Hydrolysis of 2-Hydroxypropyl-p-nitrophenyl phosphate

Ibrahim

2009

J Inorg Organomet Polym

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“…All nucleotides were purchased from Sigma. The nitrophenyl ester 4 was prepared as described (16). Compound 5 was prepared in 82% yield by the reaction of /3-cyclodextrin-6-tosylate with diethylenetriamine (Scheme II), as described by Matsumoto and Komiyama (15 All metal salts were obtained from Aldrich.…”

Section: Methodsmentioning

confidence: 99%

Effects of metal ions, including Mg2+ and lanthanides, on the cleavage of ribonucleotides and RNA model compounds.

Breslow

Huang

1991

Proc. Natl. Acad. Sci. U.S.A.

156

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The cyclization/cleavage of 3',5"-uridyluridine to form 2',3'-cycfic uridylic acid is very effectively catalyzed by Eu3', and the cyclization/cleavage of the l-pnitrophenyl phosphate ester of propane-1,2-diol also shows strong metal ion catalysis by Eu3+, Tb3+, and Yb3+. It also shows moderate catalysis by Mg2', but not by Ca2+; Zn2+ and Pb2+ are also good catalysts. Various ligands activate these reactions further, and imidazole apparently acts as an additional base catalyst. Some cyclodextrin derivatives act to bind both the substrate and the metal ion but, contrary to what is reported elsewhere, there is no strong selectivity among nucleotides that can be ascribed to cyclodextrin binding.Mechanistic studies on the cleavage of RNA (1) and of the representative dinucleotides UpU (2, 3) and ApA (4) have been described. Most ofthis work has focused on catalysis by imidazole buffers; the components imidazole and imidazolium ion are the major catalytic groups in the enzyme ribonuclease A. The preferred mechanism for cleavage of poly(U), of 3',5"-UpU (1), and of 3',5"-ApA involved protonation of the phosphate anion, followed by imidazolepromoted cyclization to form a phosphorane and then imidazole-catalyzed conversion ofthat phosphorane to the 2',3'-cyclic phosphate product characteristically formed during chemical or enzymatic cleavage of RNA (Scheme I). The evidence that ribonuclease A uses a closely related mechanism, but not the standard one found in textbooks, was pointed out, except that what is sequential in simple chemical catalysis becomes simultaneous in the enzyme (2, 3). Recently, calculated reaction paths (5) for the enzyme have supported our proposal.Although ribonuclease A does not use metal ions for catalysis, many reactions of RNA and DNA do involve metals. Thus we examined the effectiveness, and mechanism of action, of Zn2+ in the cleavage of two models for RNA (2). In one system (Scheme HA), the cyclization/cleavage of 3',5"-UpU 1 was studied; this is the same reaction in which the catalysis by imidazole buffers that led to our mechanistic proposals for the enzyme was observed (3). UpU is reallyjust a small piece of RNA. Under some conditions the slow step is the cyclization of compound 1 to form a phosphorane intermediate (2); under other conditions compound 2 is rapidly and reversibly formed, and its decomposition to form the product compound 3 is the slow step. We have shown that compound 2 is also the intermediate in the rearrangement of compound 1 to its 2',5" isomer.The second system (Scheme IIB) involves the cyclization/ cleavage of a simpler analog (4). In this system, the rate determining step is always the first step, in which the hydroxyl group adds to the phosphate to form a phosphorane, since the nitrophenoxide ion is such a good leaving group that forward decomposition of the phosphorane is always faster than the reverse of the first step, reopening of the phosphorane to form starting material. The cyclization/cleavage of compound 4 is convenient to follow by UV spectroscopy,...

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“…VR-SCOSMO attack barriers compare favorably to those calculated with the M06-2X/6-311++G(3df,2p)//M06-2X/6-311++G(d,p) PCM model 19 as well as to the known experiments. 76,77 It should be noted, however, that the experiments presented here examine reactions with sightly different chemical structures than those which have been computed in this manuscript. Specifically, Expt.…”

Section: B Phosphoryl Transfer Reactionsmentioning

confidence: 98%

VR-SCOSMO: A smooth conductor-like screening model with charge-dependent radii for modeling chemical reactions

Kuechler

Giese

York

2016

The Journal of Chemical Physics

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To better represent the solvation effects observed along reaction pathways, and of ionic species in general, a charge-dependent variable-radii smooth conductor-like screening model (VR-SCOSMO) is developed. This model is implemented and parameterized with a third order density-functional tight binding quantum model, DFTB3/3OB-OPhyd, a quantum method which was developed for organic and biological compounds, utilizing a specific parameterization for phosphate hydrolysis reactions. Unlike most other applications with the DFTB3/3OB model, an auxiliary set of atomic multipoles is constructed from the underlying DFTB3 density matrix which is used to interact the solute with the solvent response surface. The resulting method is variational, produces smooth energies, and has analytic gradients. As a baseline, a conventional SCOSMO model with fixed radii is also parameterized. The SCOSMO and VR-SCOSMO models shown have comparable accuracy in reproducing neutral-molecule absolute solvation free energies; however, the VR-SCOSMO model is shown to reduce the mean unsigned errors (MUEs) of ionic compounds by half (about 2-3 kcal/mol).

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1207. Hydrolysis of hydroxyalkyl phosphate esters: effect of changing ester group

Cited by 157 publications

References 0 publications

A Novel Dinucleating Ligand-Containing Hexabenzimidazoles and Its Dinuclear Zinc Complex Bridged by a Carboxylate Group for the Hydrolysis of 2-Hydroxypropyl-p-nitrophenyl phosphate

A Novel Dinucleating Ligand-Containing Hexabenzimidazoles and Its Dinuclear Zinc Complex Bridged by a Carboxylate Group for the Hydrolysis of 2-Hydroxypropyl-p-nitrophenyl phosphate

Effects of metal ions, including Mg2+ and lanthanides, on the cleavage of ribonucleotides and RNA model compounds.

VR-SCOSMO: A smooth conductor-like screening model with charge-dependent radii for modeling chemical reactions

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