Phosphate Diester Hydrolysis Research Articles

Phosphodiesterase Activity of Alkaline Phosphatase in ATP-initiated Ca2+ and Phosphate Deposition in Isolated Chicken Matrix Vesicles

Inorganic pyrophosphate is a potent inhibitor of bone mineralization by preventing the seeding of calcium-phosphate complexes. Plasma cell membrane glycoprotein-1 and tissue nonspecific alkaline phosphatase were reported to be antagonistic regulators of mineralization toward inorganic pyrophosphate formation (by plasma cell membrane glycoprotein-1) and degradation (by tissue nonspecific alkaline phosphatase) under physiological conditions. In addition, they possess broad overlapping enzymatic functions. Therefore, we examined the roles of tissue nonspecific alkaline phosphatase within matrix vesicles isolated from femurs of 17-day-old chick embryos, under conditions where these both antagonistic and overlapping functions could be evidenced. Addition of 25 microM ATP significantly increased duration of mineralization process mediated by matrix vesicles, while supplementation of mineralization medium with levamisole, an alkaline phosphatase inhibitor, reduces the ATP-induced retardation of mineral formation. Phosphodiesterase activity of tissue nonspecific alkaline phosphatase for bis-p-nitrophenyl phosphate was confirmed, the rate of this phosphodiesterase activity is in the same range as that of phosphomonoesterase activity for p-nitrophenyl phosphate under physiological pH. In addition, tissue nonspecific alkaline phosphatase at pH 7.4 can hydrolyze ADPR. On the basis of these observations, it can be concluded that tissue nonspecific alkaline phosphatase, acting as a phosphomonoesterase, could hydrolyze free phosphate esters such as pyrophosphate and ATP, while as phosphodiesterase could contribute, together with plasma cell membrane glycoprotein-1, in the production of pyrophosphate from ATP.

Hydrolysis of phosphate diester catalysed by transition metal complexes of a salicylaldimine Schiff base bearing dibenzo-18-crown-6

A new crowned Schiff base ligand and its cobalt(II) and manganese(III) complexes were synthesised and characterised. These complexes were used to catalyse the hydrolysis of bis(4-nitrophenyl) phosphate (BNPP) in order to mimic the action of hydrolytic metalloenzymes. The kinetics and the mechanism of the titled reactions were investigated. The change of the characteristic ultraviolet spectra of the reaction systems was also analysed. A kinetic mathematical model of BNPP cleavage catalysed by the complexes is proposed. The function of the crown ether ring and the effects of the reaction conditions on the catalytic hydrolysis of BNPP are discussed.

My Brief Encounter with the Phosphoinositides and IP3

. Before describing thisresearch, however, I should say how that choice came about. While in graduate school at theUniversity of Wisconsin, I had had the good fortune to study under Karl Paul Link, who waswidely renowned for his discovery of dicumarol and the synthesis of related blood anticoagu-lants such as warfarin, work that was recognized with two Lasker Awards (1). On the side,however, Link remained a carbohydrate chemist at heart, a hobby that had grown out of hisstudies on plant polysaccharides and uronic acids while a student and then a young facultymember. In fact, Stanford Moore had completed his doctoral dissertation with Link on amethod for characterizing aldo-monosaccharides as benzimidazole derivatives (2).I arrived at Madison in the fall of 1946, fresh from a stint in the United States Navy, andI found Link’s laboratory bursting at the seams with about 15 ex-GIs, all hard at work tryingto make up for lost time. During earlier investigations on the structure-function relationshipof coumarin anticoagulants, an attempt to synthesize the glucoside of dicumarol had beenfrustrated because the acetylated intermediate was degraded in alkali under conditions usedfor deacetylation (3). Because glycosides are acetals, which are typically acid-labile andalkali-stable, I found the anomaly intriguing and decided to study a variety of syntheticcompounds in an effort to understand the structural basis for alkali sensitivity (4). Thisresearch formed the core of my doctoral dissertation, and although I failed to recognize it at thetime, the chance exposure to carbohydrate chemistry was to have a lasting influence on thedirection my career would take.I continued my indoctrination in sugar chemistry during a postdoctoral year in Edinburgh,Scotland, with E. G. V. Percival in the new Department of Chemistry at Kings Buildingsheaded by Edwin Hirst. This was a time of economic depression in Britain, which was stillsuffering the aftermath of the war, and I discovered that I had left a well equipped laboratoryin Madison to engage an unexpectedly primitive research environment. Wisely I did not letthis change in fortunes discourage me. Instead I undertook a project dealing with the structureof maple sapwood starch and did the best that I could with the available facilities (5). Myefforts were well rewarded because, in the process, I became adept at the uses of analytical andpreparative filter paper and cellulose column chromatography, skills that were to be extremelyvaluable in my later research. The greatest challenge to my ingenuity, however, was toconstruct an electric stirring device from a small board-mounted motor, a couple of woodenpulleys, a piece of string, and a glass rod. The speed of the motor was regulated by adjustinglight bulbs that were wired in series with the power cord to draw off electricity, a crude buteffective method of control. I have always enjoyed working with my hands, so this mundaneproject even took on a certain appeal.Living in a new environment always has its fringe benefits. While in Edinburgh, I developeda special affection for the Scots and a better understanding for the lingering resentment that

Mononuclear Co(III)‐complex promoted phosphate diester hydrolysis: dependence of reactivity on the leaving group

AbstractThe TrpnCo(III)(OH)(OH2)‐promoted hydrolysis of a range of methyl aryl phosphate diesters was investigated at 37°C and I = 0.1 M (NaClO4). The pH–rate profile confirms that the aqua‐hydroxy form of the complex is the only kinetically significant ionic form. At pH 6.9, all the reactions are first order in both diester and Co(III) complex. Plotting the second‐order rate constant for Co(III) complex‐promoted hydrolysis against the pKa of the leaving aryloxy group revealed a bent LFER indicating a change in rate‐limiting step. This is discussed in terms of either a change from rate‐limiting hydrolysis to rate‐limiting binding or the presence of a phosphorane intermediate. Copyright © 2004 John Wiley & Sons, Ltd.

Phosphate diester hydrolysis in biological relevant compounds by dinuclear metal complexes

The dinuclear Ni2+ and Zn2+ complexes of 1,1′-[(1H-pyrazole-3,5-diyl)bismethylene]-bis(octahydro-1H-1,4,7-triazonine) induce phosphate diester hydrolysis in biological relevant substrates such as thymidine 5′-monophosphate 4-nitrophenylester (TMPNP), guanosine (2′-3′) cyclic phosphate ((2′-3′)cGMP), guanylyl (2′-5′) guanosine ((2′-5′)GpG), adenylyl (3′-5′) adenosine ((3′-5′)ApA), and (2′-deoxy)adenylyl (3′-5′) (2′-deoxy)adenosine ((3′-5′)dApdA). Quantitative measurements of the hydrolysis of TMPNP indicate a Michaelis–Menten mechanism in which the substrate is bound by the dinuclear complex and is hydrolyzed by an intramolecular attack of a coordinated OH− group. Qualitative HPLC measurements of the hydrolysis of the dinucleotide show that in the case of (2′-5′)GpG a cyclic phosphate is formed which then hydrolyses to 2′-GMP and 3′-GMP. The hydrolysis of (2′-3′)cGMP also gave, induced by the dinuclear Zn2+ complex, 2′-GMP and 3′-GMP.

Phosphate Diester Hydrolysis and DNA Damage Promoted by Newcis-Aqua/Hydroxy Copper(II) Complexes Containing Tridentate Imidazole-rich Ligands

The tridentate Schiff base [(2-(imidazol-4-yl)ethyl)(1-methylimidazol-2-yl)methyl)imine (HISMIMI) and its reduced form HISMIMA were synthesized and characterized, as well their mononuclear cis-dihalo copper(II) complexes 1 and 2, respectively. In addition, the dinuclear [CuII(mu-OH)2CuII](2+) complexes (3) and (4) obtained from complexes 1 and 2, respectively, were also isolated and characterized by several physicochemical techniques, including magnetochemistry, electrochemistry, and EPR and UV-vis spectroscopies. The crystal structures of 1 and 2 were determined by X-ray crystallography and revealed two neutral complexes with their tridentate chelate ligands meridionally coordinated. Completing the coordination spheres of the square-pyramidal structures, a chloride ion occupies the apical position and another is bonded in the basal plane. In addition, complexes 1 and 2 were investigated by infrared, electronic, and EPR spectroscopies, cyclic voltammetry, and potentiometric equilibrium studies. The hydrolytic activity on phosphate diester cleavage of 1 and 2 was investigated utilizing 2,4-BDNPP as substrate. These experiments were carried out at 50 degrees C, and the data treatment was based on the Michaelis-Menten approach, giving the following kinetic parameters (complex 1/complex 2): vmax (mol L(-1) s(-1))=16.4x10(-9)/7.02x10(-9); KM (mol L(-1))=17.3x10(-3)/3.03x10(-3); kcat (s(-1))=3.28x10(-4)/1.40x10(-4). Complex 1 effectively promoted the hydrolytic cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions, with a rate constant of 0.28 h(-1) for the decrease of form I, which represents about a 10(7) rate increase compared with the estimated uncatalyzed rate of hydrolysis.

Highly efficient phosphate diester hydrolysis and DNA interaction by a new unsymmetrical Fe IIINi II model complex

A new heterodinuclear mixed valence complex [Fe IIINi II(BPBPMP)(OAc) 2]ClO 4 1 with the unsymmetrical N 5O 2 donor ligand 2-bis[{(2-pyridylmethyl)-aminomethyl}-6-{(2-hydroxybenzyl)(2-pyridylmethyl)}-aminomethyl]-4-methylphenol (H 2BPBPMP) has been synthesized and characterized. 1 crystallizes in the monoclinic system, space group P2 1/ n, a=12.497(2), b=18.194(4), c=16.929(3) Å, β=94.11(3)°, V=3839.3(12) Å 3 and has an Fe IIINi II(μ-phenoxo)-bis(μ-carboxylato) core. Solution studies of 1 indicate that a pH-induced change in the bridging acetate occurs and the formation of an active [(OH)Fe III(μ-OH)Ni II(OH 2)] + species as the catalyst for phosphate diester hydrolysis and DNA interaction is proposed. In addition, the results presented here suggest that Ni II would be a good candidate as a substitute of M II in purple acid phosphatases.

Dynamic evidence for metal ion catalysis in the reaction mediated by a flap endonuclease.

On the basis of structural work, metal ions are proposed to play a catalytic role in reactions mediated by many phosphoryl transfer enzymes. To gain dynamic support for such mechanisms, the role of metal ion cofactors in phosphate diester hydrolysis catalysed by a flap endonuclease has been studied. The pH maximal rate profiles were measured in the presence of various metal ion cofactors; in each case, a single ionic form of the enzyme/cofactor accounts for the pH dependence. The kinetic pK(a)s display good correlation with the acidity of the corresponding hexahydrated metal ions, which strongly suggests a role for metal-bound hydroxide, or its equivalent ionic species, in the reaction. Comparing rates of reaction in the pH-independent regions, a small negative beta(nuc) value is observed. This suggests that expected trends in the nucleophilicity of the various metal-bound hydroxides are balanced by a second form of metal ion catalysis that is related to the acidity of the hexahydrated metal ion. This is likely to be either electrophilic catalysis or leaving group activation.

An altered mechanism of hydrolysis for a metal-complexed phosphate diester.

Isotope effects in the nucleophile and in the leaving group were measured to gain information about the mechanism and transition state of the hydrolysis of methyl p-nitrophenyl phosphate complexed to a dinuclear cobalt complex. The complexed diester undergoes hydrolysis about 1011 times faster than the corresponding uncomplexed diester. The kinetic isotope effects indicate that this rate acceleration is accompanied by a change in mechanism. A large inverse 18O isotope effect in the bridging hydroxide nucleophile (0.937 +/- 0.002) suggests that nucleophilic attack occurs before the rate-determining step. Large isotope effects in the nitrophenyl leaving group (18Olg = 1.029 +/- 0.002, 15N = 1.0026 +/- 0.0002) indicate significant fission of the P-O ester bond in the transition state of the rate-determining step. The data indicate that in contrast to uncomplexed diesters, which undergo hydrolysis by a concerted mechanism, the reaction of the complexed diester likely proceeds via an addition-elimination mechanism. The rate-limiting step is expulsion of the p-nitrophenyl leaving group from the intermediate, which proceeds by a late transition state with extensive bond fission to the leaving group. This represents a substantial change in mechanism from the hydrolysis of uncomplexed aryl phosphate diesters.

Hydrolytic activity of a dinuclear copper(II,II) complex in phosphate diester and DNA cleavage

The hydrolysis of the phosphate diester bis(2,4-dinitrophenyl) phosphate promoted by the dinuclear copper (II,II) complex [Cu2(H2bbppnol)(μ-CH3COO)(H2O)2)]Cl2·2H2O 1 (Inorg. Chim. Acta 281 (1998) 111) in aqueous–methanol solution at 50°C was examined in detail. A pH dependence on the reaction rate was observed and the pKa value calculated from the pH-rate profile is in good agreement with that determined by potentiometric titration, indicating that deprotonation of one of the two water-coordinated molecules in the complex must occur to form the active catalyst. The rate of phosphate diester hydrolysis was studied as a function of catalyst and substrate concentrations and a mechanism for the hydrolysis reaction based on intramolecular hydroxide attack on the metal-coordinated phosphate is proposed. A rate enhancement factor of 26 was calculated relative to that measured for the uncatalyzed reaction under identical conditions. The complex effectively promoted the cleavage of double-strand plasmid and genomic DNA, at physiological pH and temperature. Studies into the mechanism strongly suggest that the dinuclear copper (II,II) complex mediates a hydrolytic attack on the phosphodiester backbone through cooperativity between the two metal centers, in agreement with the mechanism proposed for the reaction of 1 with the model substrate bis(2,4-dinitrophenyl) phosphate.

Theoretical studies on the hydrolysis of phosphate diesters in the gas phase, solution, and RNase A

AbstractDensity functional theory, polarizable continuum models and semiempirical hybrid quantum mechanical/molecular mechanical (QM/MM) calculations were applied to the hydrolysis of phosphate diesters in the gas phase, in solution, and in the enzyme RNase A. Neutralization of the negative charge of the pentacovalent phosphorane intermediates provides a substantial stabilization of the transition‐state structures in the gas phase. Inclusion of solvent effects on the phosphate/phosphorane species was critical to reproducing the trends in reactivity observed experimentally. Finally, the catalytic mechanism for the hydrolysis of uridine 2′,3′‐cyclic phosphate by RNase A was studied by QM/MM calculations. Our results suggest that the rate‐limiting transition state of the reaction corresponds to the approach of a water molecule to the phosphate and its activation by His119. Thus, His119 acts as a generalized base for the reaction. The water attack leads to a pentacovalent phosphorane transition state of formal charge −2; this excess of negative charge in the transition state is stabilized by a number of positively charged residues including His12 and Lys41. In the second stage of the reaction, the phosphorane is converted into products. This part of the reaction proceeds without a detectable barrier, and it is facilitated by a proton transfer from Lys41 to the departing O2′. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001

Phosphate diester hydrolysis within a highly reactive dinuclear cobalt(iii) complex. Ligand effect on reactivity, transition state and dissociation

The hydrolysis of methyl aryl phosphate diesters coordinated to a dinuclear Co(III) complex ([Co2(tame)2(OH)2{O2P(OAr)(OMe)}]3+; tame = 1,1,1-tris(aminomethyl)ethane; 2) has been studied in aqueous solution at 25 °C. Hydrolysis of the phosphate diester is base catalysed and occurs 30 to 60 fold faster than in analogous complexes where tame is replaced by 1,4,7-triazacyclononane (tacn) (1). The second order rate constants for base catalysed hydrolysis of 2 are highly sensitive to the basicity of the aryloxy leaving group with βlg = −1.29 ± 0.03. This leaving group dependence is similar to that of 1 (βlg = −1.38 ± 0.01), showing that the ligand affects reactivity without greatly altering the transition state at phosphorus. The slight decrease in βlg is consistent with previous rationalisations of this high sensitivity. Dimethyl phosphate coordinated to both types of complex (3, tame; 4, tacn) only dissociates from the complex, with no hydrolysis. Base catalysed dissociation is slower with tame (3 20 fold slower than 4) but the pH independent reaction is faster (3 10 fold faster than 4). These data suggest that the reactivity and turnover properties of these dinuclear complexes may be tuned rationally and independently.

Copper(II) complexes of novel N-alkylated derivatives of cis,cis-1,3,5-triaminocyclohexane. 2. Metal-promoted phosphate diester hydrolysis.

Aqueous copper(II) N,N',N' '-trimethyl-cis,cis-1,3,5-triaminocyclohexane (Cu(tach-Me(3))(2+)(aq)) promotes the hydrolysis of activated phosphate diesters in aqueous medium at pH 7.2. This complex is selective for cleavage of the phosphate diester sodium bis(p-nitrophenyl) phosphate (BNPP), the rate of hydrolysis of the monoester disodium p-nitrophenyl phosphate being 1000 times slower. The observed rate acceleration of BNPP hydrolysis is slightly greater than that observed for other Cu(II) complexes, such as [Cu([9]aneN(3))Cl(2)] ([9]aneN(3) identical with 1,4,7-triazacyclononane). The rate of hydrolysis is first-order in phosphate ester at low ester concentration and second-order in [Cu(tach-Me(3))](2+)(aq), suggesting the involvement of two metal complexes in the mechanism of substrate hydrolysis. The reaction exhibits saturation kinetics with respect to BNPP concentration according to a modified Michaelis-Menten mechanism: 2CuL + S <==> LCu-S-CuL --> 2CuL + products (K(M) = 12.3 +/- 1.8 mM(2), k(cat) = (4.0 +/- 0.4) x 10(-)(4) s(-1), 50 degrees C) where CuL (triple bond) [Cu(tach-Me(3))](2+), S (triple bond) BNPP, and LCu-S-CuL is a substrate-bridged dinuclear complex. EPR data indicate that the dicopper complex is formed only in the presence of BNPP; the active LCu-S-CuL intermediate species then slowly decays to products, regenerating monomeric CuL.

Phosphodiester hydrolysis by lanthanide complexes of bis-tris propane.

Potentiometric titrations of the mixtures of lanthanide(III) perchlorates and bis-Tris propane (BTP) reveal formation of dinuclear hydroxo complexes M2(BTP)2(OH)n(6-n), where M = La(III), Pr(III), Nd(III), Eu(III), Gd(III), and Dy(III) and n = 2, 4, 5, or 6, in the pH range 7-9. ESI-MS data confirm the presence of dinuclear species. Kinetics of the hydrolysis of bis(4-nitrophenyl) phosphate (BNPP), mono-4-nitrophenyl phosphate (NPP), and 4-nitrophenyl acetate (NPA) in the lanthanide(III)-BTP systems has been studied at 25 degrees C in the pH range 7-9. The second-order rate constants for the hydrolysis of BNPP by individual lanthanide hydroxo complexes have been estimated by using the multiple regression on observed rate constants obtained at variable pH. For a given metal, the rate constants increase with increasing in the number n of coordinated hydroxide ions. In a series of complexes with a given n, the second-order rate constants decrease in the order La > Pr > Nd > Eu > Gd > Dy. Hydrolysis of NPP follows Michaelis-Menten-type "saturation" kinetics. This difference in kinetic behavior can be attributed to stronger binding of NPP dianion than BNPP monoanion to the lanthanide(III) species. Activities of lanthanide complexes in the hydrolysis of NPA, which is 10(6) times more reactive than BNPP in alkaline or aqueous hydrolysis, are similar to those in BNPP hydrolysis indicating unique capability of lanthanide(III) cations to stabilize the transition state of phosphate diester hydrolysis. Results of this study are analyzed together with literature data for other metal cations in terms of the Brønsted correlation and transition state-catalyst complexation strength.

Functional Interrelationships in the Alkaline Phosphatase Superfamily: Phosphodiesterase Activity of Escherichia coli Alkaline Phosphatase

Escherichia coli alkaline phosphatase (AP) is a proficient phosphomonoesterase with two Zn(2+) ions in its active site. Sequence homology suggests a distant evolutionary relationship between AP and alkaline phosphodiesterase/nucleotide pyrophosphatase, with conservation of the catalytic metal ions. Furthermore, many other phosphodiesterases, although not evolutionarily related, have a similar active site configuration of divalent metal ions in their active sites. These observations led us to test whether AP could also catalyze the hydrolysis of phosphate diesters. The results described herein demonstrate that AP does have phosphodiesterase activity: the phosphatase and phosphodiesterase activities copurify over several steps; inorganic phosphate, a strong competitive inhibitor of AP, inhibits the phosphodiesterase and phosphatase activities with the same inhibition constant; a point mutation that weakens phosphate binding to AP correspondingly weakens phosphate inhibition of the phosphodiesterase activity; and mutation of active site residues substantially reduces both the mono- and diesterase activities. AP accelerates the rate of phosphate diester hydrolysis by 10(11)-fold relative to the rate of the uncatalyzed reaction [(k(cat)/K(m))/k(w)]. Although this rate enhancement is substantial, it is at least 10(6)-fold less than the rate enhancement for AP-catalyzed phosphate monoester hydrolysis. Mutational analysis suggests that common active site features contribute to hydrolysis of both phosphate monoesters and phosphate diesters. However, mutation of the active site arginine to serine, R166S, decreases the monoesterase activity but not the diesterase activity, suggesting that the interaction of this arginine with the nonbridging oxygen(s) of the phosphate monoester substrate provides a substantial amount of the preferential hydrolysis of phosphate monoesters. The observation of phosphodiesterase activity extends the previous observation that AP has a low level of sulfatase activity, further establishing the functional interrelationships among the sulfatases, phosphatases, and phosphodiesterases within the evolutionarily related AP superfamily. The catalytic promiscuity of AP could have facilitated divergent evolution via gene duplication by providing a selective advantage upon which natural selection could have acted.

Catalytic Hydrolysis of Phosphate Diester with Metal Complexes of Macrocyclic Tetraamine in Comicellar Solution

AbstractFour novel pyridine or benzene ring‐containing pendant macrocyclic dioxotetraamines 2,6‐dixo‐l,4,7,10‐tetraazacyclododecane ligands have been synthesized. Their metal complexes have been investigated as catalysts for the hydrolysis of bis(p‐nitrophenyl) phosphate (BNPP) in aqueous comicellar solution. The results indicate mat the hydrophobic interaction between substrate and metal complex, the nature of transition metal ion, and the micellar microenvironment are important factors for the hydrolysis of BNPP. Large rate enhancement (up to over two‐three orders of magnitude) employing 5 has been observed.

Base catalysed phosphate diester hydrolysis

The rate of attack of hydroxide on dialkyl phosphate diesters is far slower than previously estimated, allowing us to estimate the stability of the diester link in DNA and showing that ethylene phosphate is 1011 fold more reactive towards attack by hydroxide than an acyclic diester (1000 fold more than previously estimated).

A model for Zn II-containing-β-lactamase: synthesis, X-ray crystal structure of a zinc(II) complex bearing thiol groupand hydrolysis of phosphate diester

A novel N 3S 1 typed tripodal ligand bearing an SH group, N-(mercaptoethyl)-di(2-pyridylmethyl)amine, DPASH, was prepared and its zinc(II) complex, [Zn II(DPAS)Cl], was structurally characterized by X-ray crystallography. [Zn II(DPAS)Cl] promoted hydrolysis of sodium bis( p-nitrophenyl)hydrogenphosphate), BNP −.

Phosphate diester hydrolysis by mono- and dinuclear lanthanum complexes with an unusual third-order dependence.

A series of mono- and dinuclear lanthanum complexes of 15,31-dimethyl-3,11,19,27,33,35-hexaazapentacyclo[27.3.1.1.(5,9)1,(13,17). 1(21,25)]hexatriaconta-5,7,9(33),13,15,17(34),21,23,25(35),29,31, 1(36)-dodecaene-34,36-diol (24RBPyBC, L) have been defined in solution. Their ability to hydrolyze bis(4-nitrophenyl) phosphate, a phosphate diester, was studied. The various metal-coordinated hydroxide nucleophiles that form in solution attack the substrate in the hydrolysis reaction. The dihydroxo dilanthanum complex, L-2La-2(OH), is the most effective catalyst. Its rate constant is 75 times larger than the rate constant for the monohydroxo dilanthanum complex, L-2La-OH. The mononuclear complexes are not as successful as the dinuclear complexes because they have fewer metal ions per complex to act as Lewis acids. They also cannot generate hydroxide nucleophiles at low pH values like the dinuclear complexes can. The reaction has an unusual third-order dependence on the catalyst concentration which is valid for the dinuclear complexes as well as the mononuclear complexes. This implies a mechanism where a metal-coordinated hydroxide nucleophile attacks the phosphorus of the substrate on the side opposite the negatively charged oxygens.

ChemInform Abstract: Recent Studies of Nucleophilic, General‐Acid, and Metal Ion Catalysis of Phosphate Diester Hydrolysis

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.