Leaving group assistance in the La3+-catalyzed cleavage of dimethyl (o-methoxycarbonyl)aryl phosphate triesters in methanol.

The catalytic methanolysis of a series of dimethyl aryl phosphate triesters where the aryl groups contain an o-methoxycarbonyl (o-CO2Me) substituent (4a-i) was studied at 25 degrees C in methanol containing La3+ at various concentrations and (s)(s)pH. Determination of the second-order rate constant for La3+(2)-catalyzed cleavage of substrate 4a (dimethyl (o-methoxycarbonyl)phenyl phosphate) as a function of (s)(s)pH was assessed in terms of a speciation diagram that showed that the process was catalyzed by La3+(2)(-OCH3)x dimers, where x = 1-5, that exhibit only a 5-fold difference in activity between all the species. The second-order catalytic rate constants (k2(La)) for the catalyzed methanolysis of 4a-i at (s)(s)pH 8.7 fit a Brønsted relationship of log k2(La) = (-0.82 +/- 0.11)(s)(s)pKa(lg) + (11.61 +/- 1.48), where the gradient is shallower than that determined for a series of dimethyl aryl phosphates that do not contain the o-CO2Me substituent, log k2(La) = (-1.25 +/- 0.06)(s)(s)pKa(lg) + (16.23 +/- 0.75). Two main observations are that (1) the o-CO2Me group preferentially accelerates the cleavage of the phosphate triesters with poor leaving groups relative to those with good leaving groups and (2) it provides an increase in cleavage rate relative to those of comparable substrates that do not have that functional group, e.g., k2(La)(dimethyl o-(methoxycarbonyl)phenyl phosphate)/k2(La)(dimethyl phenyl phosphate) = 60. Activation parameters for the La3+(2)-catalyzed methanolysis of 4a and dimethyl 4-nitrophenyl phosphate show respective DeltaH(double dagger) (DeltaS(double dagger)) values of 3.3 kcal/mol (-47 cal/mol x K) and 0.7 kcal/mol (-46.5 cal/mol x K). The data are analyzed in terms of a concerted reaction where the catalytic complex (La3+(2)(-OCH3)(x-1)) binds to the three components of a rather loose transition state composed of a nucleophile CH3O-, a nucleofuge -OAr, and a central (RO)2P(2+)-O(-) in a way that provides leaving group assistance to the departing aryloxy group.

[1]  L. Ginjaar,et al.  On the reactivity of organophosphorus compounds. I. The alkaline hydrolysis of some dialkyl p‐nitrophenyl phosphates , 2010 .

[2]  B. S. Souza,et al.  Efficient intramolecular general-acid catalysis of the reactions of alpha-effect nucleophiles and ammonia oxide with a phosphate triester. , 2009, Journal of the American Chemical Society.

[3]  A. A. Neverov,et al.  Dissociative solvolytic cleavage of methyl (ortho-carboxymethyl)aryl phosphate diesters mediated by Yb3+ in methanol gives a 10(12)-fold rate acceleration attributable to leaving group assistance. , 2009, Journal of the American Chemical Society.

[4]  S. Almo,et al.  Structure of diethyl phosphate bound to the binuclear metal center of phosphotriesterase. , 2008, Biochemistry.

[5]  C. Liu,et al.  A simple DNase model system comprising a dinuclear Zn(II) complex in methanol accelerates the cleavage of a series of methyl aryl phosphate diesters by 10(11)-10(13). , 2008, Journal of the American Chemical Society.

[6]  A. K. Yatsimirsky,et al.  Simplified speciation and improved phosphodiesterolytic activity of hydroxo complexes of trivalent lanthanides in aqueous DMSO. , 2008, Inorganic chemistry.

[7]  D. Ollis,et al.  In crystallo capture of a Michaelis complex and product-binding modes of a bacterial phosphotriesterase. , 2008, Journal of molecular biology.

[8]  R. S. Brown,et al.  The dinuclear Zn(II) complex catalyzed cyclization of a series of 2-hydroxypropyl aryl phosphate RNA models: progressive change in mechanism from rate-limiting P-O bond cleavage to substrate binding. , 2007, Journal of the American Chemical Society.

[9]  Jiali Gao,et al.  The reaction mechanism of paraoxon hydrolysis by phosphotriesterase from combined QM/MM simulations. , 2007, Biochemistry.

[10]  D. Gin,et al.  Effect of ligand modifications and varying metal-to-ligand ratio on the catalyzed hydrolysis of phosphorus triesters by bimetallic tetrabenzimidazole complexes , 2007 .

[11]  F. Raushel,et al.  Activation of the binuclear metal center through formation of phosphotriesterase-inhibitor complexes. , 2007, Biochemistry.

[12]  F. Nome,et al.  Efficient intramolecular general acid catalysis of nucleophilic attack on a phosphodiester. , 2006, Journal of the American Chemical Society.

[13]  Elisa Collado-Fregoso,et al.  Phosphate ester hydrolysis by hydroxo complexes of trivalent lanthanides stabilized by 4-imidazolecarboxylate. , 2006, Inorganic chemistry.

[14]  R. S. Brown,et al.  Catalytic decomposition of simulants for chemical warfare V agents: highly efficient catalysis of the methanolysis of phosphonothioate esters. , 2006, Angewandte Chemie.

[15]  D. Herschlag,et al.  Alkaline phosphatase mono- and diesterase reactions: comparative transition state analysis. , 2006, Journal of the American Chemical Society.

[16]  R. S. Brown,et al.  Metal ion promoted transesterifications of carboxylate esters. A structure/activity study of the efficacy of Zn2+ and La3+ to catalyze the methanolysis of some aryl and aliphatic esters. , 2005, Organic & biomolecular chemistry.

[17]  D. Rinaldi,et al.  Theoretical studies of the hydroxide-catalyzed P-O cleavage reactions of neutral phosphate triesters and diesters in aqueous solution: examination of the changes induced by H/Me substitution. , 2005, The journal of physical chemistry. B.

[18]  Roxanne E. Lewis,et al.  Mechanistic studies of La3+ and Zn2+-catalyzed methanolysis of O-ethyl O-aryl methylphosphonate esters. An effective solvolytic method for the catalytic destruction of phosphonate CW simulants. , 2005, Organic & biomolecular chemistry.

[19]  A. Hengge,et al.  The thermodynamics of phosphate versus phosphorothioate ester hydrolysis. , 2005, The Journal of organic chemistry.

[20]  A. K. Yatsimirsky.  Metal ion catalysis in acyl and phosphoryl transfer : Transition states as ligands , 2005 .

[21]  G. Gibson,et al.  Acceleration of the methanolysis of phosphate diesters promoted by La(OTf)3 The analysis of non-integer pH/rate profiles resulting from changes in metal ion speciation , 2005 .

[22]  R. S. Brown,et al.  Mechanistic studies of La3+- and Zn2+-catalyzed methanolysis of aryl phosphate and phosphorothioate triesters. Development of artificial phosphotriesterase systems. , 2005, Organic & biomolecular chemistry.

[23]  R. S. Brown,et al.  La3+-catalyzed methanolysis of O,O-diethyl S-(p-nitrophenyl) phosphorothioate and O,O-diethyl S-phenyl phosphorothioate. Millions-fold acceleration of the destruction of V-agent simulants. , 2004, Organic & biomolecular chemistry.

[24]  A. Hengge,et al.  Altered mechanisms of reactions of phosphate esters bridging a dinuclear metal center. , 2004, Journal of the American Chemical Society.

[25]  P. Wyman,et al.  Mononuclear Co(III)-complex promoted phosphate diester hydrolysis: dependence of reactivity on the leaving group† , 2004 .

[26]  F. Raushel,et al.  Mechanism for the hydrolysis of organophosphates by the bacterial phosphotriesterase. , 2004, Biochemistry.

[27]  G. Gibson,et al.  Potentiometric titration of metal ions in ethanol. , 2003, Inorganic chemistry.

[28]  R. S. Brown,et al.  Billion-fold acceleration of the methanolysis of paraoxon promoted by La(OTf)3 in methanol. , 2003, Journal of the American Chemical Society.

[29]  J. Oakeshott,et al.  Evolution of an organophosphate-degrading enzyme: a comparison of natural and directed evolution. , 2003, Protein engineering.

[30]  Nabil Asaad,et al.  Concurrent nucleophilic and general acid catalysis of the hydrolysis of a phosphate triester , 2002 .

[31]  G. Gibson,et al.  Catalysis of transesterification reactions by lanthanides Unprecedented acceleration of methanolysis of aryl and alkyl esters promoted by La(OTf)3 at neutral sspH and ambient temperatures , 2001 .

[32]  R. S. Brown,et al.  Catalysis of the methanolysis of activated amides by divalent and trivalent metal ions. The effect of Zn(2+), Co(2+), and La(3+) on the methanolysis of acetylimidazole and its (NH(3))(5)Co(III) complex. , 2001, Journal of the American Chemical Society.

[33]  B. Stec,et al.  A Model of the Transition State in the Alkaline Phosphatase Reaction* , 1999, The Journal of Biological Chemistry.

[34]  Nicholas H Williams,et al.  Structure and Nuclease Activity of Simple Dinuclear Metal Complexes: Quantitative Dissection of the Role of Metal Ions , 1999 .

[35]  Nicholas H Williams,et al.  Reactivity of Phosphate Diesters Doubly Coordinated to a Dinuclear Cobalt(III) Complex: Dependence of the Reactivity on the Basicity of the Leaving Group , 1998 .

[36]  J. Cowan.  Metal Activation of Enzymes in Nucleic Acid Biochemistry. , 1998, Chemical reviews.

[37]  P. R. Norman,et al.  Kinetic and mechanistic studies of the reaction of a range of bases and metal-hydroxo complexes with the phosphonate ester 2,4-dinitrophenyl ethyl methylphosphonate in aqueous solution , 1998 .

[38]  William N. Lipscomb,et al.  Recent Advances in Zinc Enzymology. , 1996, Chemical reviews.

[39]  T. C. Bruice,et al.  One- and Two-Metal Ion Catalysis of the Hydrolysis of Adenosine 3‘-Alkyl Phosphate Esters. Models for One- and Two-Metal Ion Catalysis of RNA Hydrolysis , 1996 .

[40]  Toshiji Tada,et al.  Thermodynamic and Kinetic Studies of Zinc(II)-Triamine Complexes as Models of CA and AP , 1996 .

[41]  T. C. Bruice,et al.  The Negative Charge of Alkyl Phosphate Diesters and The Slow-Gaited Hydrolysis of RNA and DNA. Catalysis of RNA Hydrolysis through Metal Ion Ligation to the Ester >PO2- Moiety , 1994 .

[42]  J. Steitz,et al.  A general two-metal-ion mechanism for catalytic RNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[43]  F. Raushel,et al.  Characterization of the zinc binding site of bacterial phosphotriesterase. , 1992, The Journal of biological chemistry.

[44]  T. C. Bruice,et al.  Chemistry of phosphodiesters, DNA, and models. 2. The hydrolysis of bis(8-hydroxyquinoline) phosphate in the absence and presence of metal ions , 1992 .

[45]  F. Raushel,et al.  Limits of diffusion in the hydrolysis of substrates by the phosphotriesterase from Pseudomonas diminuta. , 1991, Biochemistry.

[46]  D. Matthews,et al.  Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. , 1991, Science.

[47]  E. E. Kim,et al.  Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis. , 1991, Journal of molecular biology.

[48]  T. Steitz,et al.  Structural basis for the 3′‐5′ exonuclease activity of Escherichia coli DNA polymerase I: a two metal ion mechanism. , 1991, The EMBO journal.

[49]  M. Waring,et al.  Single transition state in the transfer of a neutral phosphoryl group between phenoxide ion nucleophiles in aqueous solution , 1990 .

[50]  D. Suck,et al.  Crystallisation and preliminary crystallographic analysis of P1 nuclease from Penicillium citrinum. , 1990, Journal of molecular biology.

[51]  J. Morrow,et al.  Hydrolysis of phosphate diesters with copper(II) catalysts , 1988 .

[52]  Salem A. Ba-Saif,et al.  Transfer of the diethoxyphosphoryl group [(EtO)2PO] between imidazole and aryloxy anion nucleophiles , 1988 .

[53]  V. E. Lewis,et al.  Mechanism and stereochemical course at phosphorus of the reaction catalyzed by a bacterial phosphotriesterase. , 1988, Biochemistry.

[54]  Andrew Williams.  Effective charge and Leffler's index as mechanistic tools for reactions in solution , 1984 .

[55]  D. Gorenstein,et al.  Multiple structure-reactivity correlations in the hydrolysis of epimeric 2-aryloxy-2-oxy-dioxaphosphorinanes. Stereoelectronic effects , 1981 .

[56]  W. Jencks.  General acid-base catalysis of complex reactions in water , 1972 .

[57]  M. Mazzarelli,et al.  [Biochemical and biophysical characteristics of phage DDVI DNA]. , 1970, Biokhimiia.

[58]  R. Wolfenden,et al.  Transition State Analogues for Enzyme Catalysis , 1969, Nature.

[59]  F. Westheimer.  Pseudo-rotation in the hydrolysis of phosphate esters , 1968 .

[60]  F. Iverson,et al.  Measurement of the affinity and phosphorylation constants governing irreversible inhibition of cholinesterases by di-isopropyl phosphorofluoridate. , 1966, The Biochemical journal.

[61]  A. Hengge.  Mechanistic Studies on Enzyme-Catalyzed Phosphoryl Transfer , 2005 .

[62]  E. Bosch,et al.  Hammett–Taft and Drago models in the prediction of acidity constant values of neutral and cationic acids in methanol† , 1999 .

[63]  R. Strömberg,et al.  The mechanism of the metal ion promoted cleavage of RNA phosphodiester bonds involves a general acid catalysis by the metal aquo ion on the departure of the leaving group , 1999 .

[64]  J. Wilkie,et al.  Stereochemical, mechanistic, and structural features of enzyme-catalysed phosphate monoester hydrolyses , 1995 .

[65]  M. Komiyama,et al.  Synergetic catalysis by two non-lanthanide metal ions for hydrolysis of diribonucleotides , 1995 .

[66]  Andrew Williams,et al.  Dependence of transition-state structure on nucleophile in the reaction of aryl oxide anions with aryl diphenylphosphate esters , 1991 .

[67]  R. Kluger,et al.  Mechanism and Catalysis of Nucleophilic Substitution in Phosphate Esters , 1989 .

[68]  C. Hall,et al.  Phosphorus stereochemistry : Mechanistic implications of the observed stereochemistry of bond forming and breaking processes at phosphorus in some 5- and 6-membered cyclic phosphorus esters , 1980 .

[69]  R. Martin.  Nucleophilicities of metal ion bound hydroxide , 1976 .

[70]  R. Bromilow,et al.  Intramolecular catalysis of phosphate triester hydrolysis. Nucleophilic catalysis by the neighbouring carboxy-group of the hydrolysis of diaryl 2-carboxyphenyl phosphates , 1972 .

[71]  A. J. Kirby,et al.  The reactivity of phosphate esters. Multiple structure–reactivity correlations for the reactions of triesters with nucleophiles , 1970 .