<b>Isotopic and Kinetic Studies of the Mechanism of Hydrolysis of Salicyl Phosphate. Intramolecular General Acid Catalysis</b>

Bender, Myron L.; Lawlor, J. M.

doi:10.1021/ja00902a031

Cited by 46 publications

(12 citation statements)

References 3 publications

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“…When the monoester 1 b is not bound to the complex, it is only hydrolyzed tenfold faster than 1 c 16. This is consistent with other data which also show that an adjacent OH group of similar p K a value to the leaving group provides only approximately tenfold rate acceleration (in carboxylic ester hydrolysis17 and phosphate triester hydrolysis18).…”

Section: Methodssupporting

confidence: 89%

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Mimicking Metallophosphatases: Revealing a Role for an OH Group with No Libido

Forconi

Williams

2002

Angew. Chem.

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Typically, descriptions of enzyme catalysis use multiple simultaneous interactions between the substrate and the active site to explain the remarkable efficiency which is normally observed. [1] This poses the intriguing question-do the different interactions operate cooperatively? That is, can a catalytic interaction have a bigger impact when it acts in concert with other complementary interactions than when it is used alone. This is difficult to mimic with simple compounds; usually when multiple interactions are introduced into a model system, it is found that they act independently rather than simultaneously, and such models generally do not rival enzyme efficiency. [2] Here we report how catalysis of phosphate monoester hydrolysis by an intramolecular OH group becomes much more effective when combined with catalysis by a dinuclear metal ion complex.We have incorporated phosphate monoesters 1 a ± c into dinuclear Co III complexes 2 a ± c. We have previously studied this type of complex as a structural and functional model for dinuclear metallophosphatases. [3] We wanted to investigate the effect of combining intramolecular general acid catalysis with this highly reactive core, as X-ray crystallography has revealed that as well as the metal ions in the active sites of metallophosphatase such as protein phosphatase-1 (PP-1) and kidney bean purple acid phosphatase (KBPAP), potentialIn summary, we have developed a new family of 1,4diphosphanes 1 with an imidazolidin-2-one backbone as chiral ligands and showed their utility in the hydrogenation of aenamides. The modular construction of this ligand class allows for wide structural diversity. Studies of this kind and mechanistic investigations are underway. Experimental SectionFor details on the synthesis of 1 a ± 1 k and their precursors, see Supporting Information.General procedure for the asymmetric hydrogenation of enamide 4: 1 (0.0074 mmol) was added to a solution of [Rh(cod) 2 ]BF 4 (2.5 mg, 0.0062 mmol; cod 1,5-cyclooctadiene) in CH 2 Cl 2 (2 mL). After the reaction mixture had been stirred at 20 8C for 20 min, enamide 4 (0.62 mmol) was added. The hydrogenation was performed at 20 8C under 1 atm of hydrogen for 12 h. The reaction mixture was passed through a short silica gel column to remove the catalyst. The enantiomeric excess and the reaction conversion were measured by chiral GC or HPLC without any further purification. The enantioselectivity was slightly decreased at a lower reaction temperature (95.7 % ee at 6 8C) or higher hydrogen pressure (95.2 % ee at 40 psi) with ligand 1 g. Other solvents such as acetone (95.6 % ee), THF (93.9 % ee), and MeOH (94.2 % ee) were also examined with 1 g as chiral ligand.[13] M.

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Section: Methodssupporting

confidence: 89%

“…Complex 1 a was obtained from Aldrich and used as received. Complexes 1 b, 1 c and 2 were synthesized according to previously reported methods 3, 16…”

Section: Methodsmentioning

confidence: 99%

Mimicking Metallophosphatases: Revealing a Role for an OH Group with No Libido

Forconi

Williams

2002

Angew. Chem.

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“…As expected, the rate of both the fY-CH and SA-P-CH reactions increases with decreasing pH. 12 The rate of the fY-CH reaction increases gradually with decreasing pH, but the rate if the SA-P-CH reaction increases suddenly at pH 7 and then more gradually as the pH decreases. Since the pK a of the phosphate is near 7, 12 the 20-fold faster rate can be attributed to intramolecular acid catalysis by the phosphate.…”

Section: Letter Syn Lettsupporting

confidence: 71%

Intramolecular Catalysis of Hydrazone Formation of Aryl-Aldehydes via ortho-Phosphate Proton Exchange

Dilek

Sorrentino

Bane

2016

Synlett

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Bioorthogonal site-specific chemical reaction to label biomolecules in vitro and in living cells is one of the most powerful and convenient tools in chemical biology. Reactive pairs frequently used for chemical conjugation are aldehydes/ketones with hydrazines/hydrazides/hydroxylamines. Although the reaction is generally specific for the two components, even in a cellular environment, the reaction is very slow under physiological conditions. Addition of a phosphate group at the ortho position of an aromatic aldehyde increases the reaction rate by an order of magnitude and enhances the aqueous solubility of the reagent and the product. We have synthesized phosphate-substituted aldehyde synthetic models to study kinetics of their reactions with hydrazines and hydrazides that contain a fluorophore. This rapid bioorthogonal reaction should therefore be potentially a very useful reaction for routine site-specific chemical ligations to study and image complex cellular processes in biological systems.

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“…Normally, such recombination rates for the proton of a phenolic hydroxyl are of the order of 1010 M-lsec-l, but with an o-carboxylate group the rate is decreased to 10' M-Isec-1, reflecting a neighboring group interaction.' For substituents that result in a ApK, between ortho and para isomers and also reduce the rate of recombination, it appears that ApK, is a crude index of the effectiveness of the catalysis, and this is consistent with the trend in the above cases (ApK, for 0-and p-COOH, 4 ing phosphate transfer in model systems have been unspectacular, if judged in terms of the observed rate accelerations (usually not greater than 60-fold at saturating metal ion concentrations). Recently, we examined the catalysis by Cu(I1) ion in the hydrolysis of the phosphate ester derived from 2-[4(5)-imidazolyl]phenylphosphate.…”

supporting

confidence: 70%

Section of Catalysis: MODEL REACTIONS FOR CATALYSIS OF PHOSPHATE AND SULFATE TRANSFER*

Benkovic

1970

Trans NY Acad Sci

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Phosphate-and sulfate-transfer reactions are found in a great variety of metabolic and biosynthetic pathways essential for the survival of the organism. Our knowledge of the detailed molecular mechanisms for these enzymecatalyzed group transfers in most cases is superficial, although a more complete visualization of the molecular events for several of these enzymes, e.g., pancreatic ribonuclease' and Escherichiu coli alkaline phosphatase,? is beginning to emerge. In these latter cases, much of the proposed mechanism is founded on results obtained in model systems, i.e., reactions designed to simulate the potential pathways available to a reactive enzyme-substrate complex. This paper documents some of our efforts aimed at elucidating possible operative mechanism €or enzymic catalysis of phosphate-and sulfate-group transfer.Numerous physical-organic studies of the hydrolytic lability of phosphate monoester monoanions have led to the postulation of a unique mechanism involving pre-equilibrium zwitterion formation followed by rate-determining expulsion of a hypothetical species, monomeric metaphosphate.2 Only in the case of a superior leaving group such as 2,4-dinitrophenol does proton transfer to form the zwitterion become partially rate-determining, as suggested by the incursion of a deuterium solvent isotope effect (klrlo/k,,20 = 1.4) and the negative deviation of the rate of hydrolysis from a linear free-energy relationship (log k,. vs. pK, of the alcohol).:' The highly reactive monomeric metaphosphate that is generated ( EQ. l ) undergoes rapid hydrolysis to phosphoric acid, with the overall result being a net transfer of a phosphoryl moiety [PO,-].One can anticipate from the mechanism in EQ. I , which requires the conversion of a potential alkoxide to the neutral-alcohol leaving group, that certain phosphate monoestcr dianions also will be hydrolytically labile provided a more acidic leaving alkoxide moiety is present. Nitro group stabilization of the *This paper was presented at a meeting of the Section on November 13, 1969. 330

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Isotopic and Kinetic Studies of the Mechanism of Hydrolysis of Salicyl Phosphate. Intramolecular General Acid Catalysis

Cited by 46 publications

References 3 publications

Mimicking Metallophosphatases: Revealing a Role for an OH Group with No Libido

Mimicking Metallophosphatases: Revealing a Role for an OH Group with No Libido

Intramolecular Catalysis of Hydrazone Formation of Aryl-Aldehydes via ortho-Phosphate Proton Exchange

Section of Catalysis: MODEL REACTIONS FOR CATALYSIS OF PHOSPHATE AND SULFATE TRANSFER*

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