Hydrolysis Of Phosphate Triesters Research Articles

Front Cover: Phosphate Triester Hydrolysis by Mononuclear Iron(III) Complexes: The Role of Benzimidazole in the Second Coordination Sphere (Eur. J. Inorg. Chem. 12/2024)

Front Cover: Phosphate Triester Hydrolysis by Mononuclear Iron(III) Complexes: The Role of Benzimidazole in the Second Coordination Sphere (Eur. J. Inorg. Chem. 12/2024)

Phosphate Triester Hydrolysis by Mononuclear Iron(III) Complexes: The Role of Benzimidazole in the Second Coordination Sphere

AbstractOver the years, phosphate ester hydrolysis catalyzed by coordination compounds has attracted extensive research on developing new bioinspired compounds. However, the literature lacks sufficient examples displaying activity toward phosphate triesters specifically, limiting the understanding of efficient strategies for the hydrolysis of this compound hydrolysis. Herein, we report preparing and characterizing three mononuclear iron(III) complexes (1, 2, and 3) and their hydrolase‐like activity. Complexes 2 and 3 have benzimidazole (BIMZ) moieties and were strategically designed to separate the BIMZ moiety from the first coordination sphere, and complex 1 (without BIMZ) was used as a reference. Several techniques provided structural information, including spectrophotometry, spectrometry, electrochemistry, elemental analysis, and 57Fe Mossbauer. Density functional theory (DFT) revealed distorted octahedral geometries due to the presence of the BIMZ groups. These groups also directly affected the protonation equilibria and catalytic activity. The phosphate triester diethyl‐2,4‐dinitrophenylphosphate (DEDNPP) hydrolysis was enhanced at least 27 times compared to the uncatalyzed reaction, with complexes 2 and 3, thus showing higher catalytic rates (kcat). Moreover, a longer carbon chain led to a higher hydrolysis rate but less interaction with substrate. These findings provide background for further investigations and the development of efficient catalysts for agrochemical degradation.

Base Mechanism to the Hydrolysis of Phosphate Triester Promoted by the Cd2+/Cd2+ Active site of Phosphotriesterase: A Computational Study.

In the present work, density functional theory (DFT) calculations at the B3LYP/6-31+G(d) and including dispersion effects were used to investigate the hydrolysis of paraoxon, using a cluster model of the active site of Cd2+/Cd2+-phosphotriesterase (PTE) from Pseudomonas diminuta. The mechanism proposed here consist of (i) Exchange of the coordinated water molecule and coordination of the substrate to the more solvent exposed Cdβ center in monodentate fashion, (ii) protonation of the μ-hydroxo bridge by the uncoordinated water molecule and in situ formation of the nucleophile, (iii) formation of a pentacoordinate intermediate with significant bond breaking to the leaving group and bond formation to the nucleophile, and (iv) protonation of the Asp301 residue and restoration of the active site through the coordination of another water molecule of the medium. The water molecules initially coordinated to the active site play a crucial role in stabilizing the transition states and the pentacoordinate intermediate. The reaction takes place in a two-step (AN + DN) mechanism, with energy barriers of 12.9 and 1.9 kcal/mol for the first and second steps, respectively, computed at the B3LYP-D3/6-311++G(2d,2p) level of theory, in excellent agreement with the experimental findings. Dispersion effects alone contribute to diminish the energy barriers as much as 26%. The base mechanism for the Cd2+/Cd2+-PTE proposed here, in conjunction with the agreement found with the experimental energetic value for the energy barrier, makes it a consistent and kinetically viable mechanistic proposal for the hydrolysis of phosphate triesters promoted by the Cd2+ substituted PTE enzyme.

Simulating the catalytic effect of a designed mononuclear zinc metalloenzyme that catalyzes the hydrolysis of phosphate triesters.

One of the greatest challenges in biotechnology and in biochemistry is the ability to design efficient enzymes. In fact, such an ability would be one of the most convincing manifestations of a full understanding of the origin of enzyme catalysis. Despite some progress on this front, most of the advances have been made by placing the reacting fragments in the proper places rather than by optimizing the preorganization of the environment, which is the key factor in enzyme catalysis. A rational improvement of the preorganization and a consistent assessment of the effectiveness of different design options require approaches capable of evaluating reliably the actual catalytic effect. In this work we examine the ability of the empirical valence bond (EVB) to reproduce the results of directed evolution improvements of the catalysis of diethyl 7-hydroxycoumarinyl by a designed mononuclear zinc metalloenzyme. Encouragingly, our study reproduced the catalytic effect obtained by directed evolution and offers a good start for further studies of this system.

Density Functional Calculations on the Alkaline Hydrolysis of Phosphate Triesters

We have performed density functional theory calculations on the alkaline hydrolysis of diethyl p-chlorophenyl phosphate and triethyl phosphate in the gas phase and in solution. It is found that the two hydrolysis reactions proceed through associative mechanism. The second step of hydrolysis reaction has a very low energy barrier fro diethyl p-chlorophenyl phosphate. For triethyl phosphate, the free energy barrier for the second step is higher both in the gas phase and in solution, indication the second step is the rate-determining step. The free energies of all stationary points and the free energy barrier for all the processes in solution are higher than those in the gas phase. Our calculations provide a comprehensive data set and allow re-interpretation of previous experimental and theoretical studies, and new experiment is proposed to trace reactions both in the gas phase and in solution.

Theoretical Study of the Importance of the Spectator Groups on the Hydrolysis of Phosphate Triesters

The spontaneous hydrolysis of a series of five triaryl and two dialkyl aryl phosphate triesters, previously studied experimentally, is examined theoretically using two different hybrid density functional methods, B3LYP and M06; two basic sets, 6-31+G(d) and 6-311++G(d,p); and the Gaussian 09 program. The B3LYP/6-31+G(d) methodology combined excellent accuracy with minor computational cost. The calculations show excellent quantitative agreement with experiment, which is best in the presence of three discrete water molecules. The results support a two-step mechanism involving a pentacovalent addition intermediate, with a lifetime of tenths of a millisecond. The rate-determining formation of this intermediate involves general base catalysis, defined by concerted proton transfers in a six-membered cyclic activated complex (TS1), which involves two hydrogen-bonded water molecules supporting a well-developed H(2)O···P bond (mean % evolution 77.83 ± 0.97). The third water molecule is hydrogen-bonded to P═O and subsequently involved in product formation via TS2. The effects on reactivity of all the groups attached to phosphorus in TS1 are examined in detail: the two non-leaving groups in particular are found to play an important role, accounting for the substantial difference in reactivity between triaryl and dialkyl aryl phosphate triesters.

Activating Water: Important Effects of Non‐leaving Groups on the Hydrolysis of Phosphate Triesters

The high rate of spontaneous hydrolysis of tris-2-pyridyl phosphate (TPP) is explained by the activating effects of the non-leaving ("spectator") groups on P-OAr cleavage, and not by intramolecular catalysis. Previous work on phosphate-transfer reactions has concentrated on the contributions to reactivity of the nucleophile and the leaving group, but our results make clear that the effects of the non-leaving groups on phosphorus can be equally significant. Rate measurements for three series of phosphate triesters showed that sensitivities to the non-leaving groups are substantial for spontaneous hydrolysis reactions, although significantly smaller for reactions with good nucleophiles. There are clear differences between triaryl and dialkyl aryl triesters in sensitivities to leaving and non-leaving groups with the more reactive triaryl systems showing lower values for both β(LG) and β(NLG). Intramolecular catalysis of the hydrolysis of TPP by the neighbouring pyridine nitrogens is insignificant, primarily because of their low basicity.

Alkaline hydrolysis of phosphate triesters in solution: Stepwise or concerted? A theoretical study

We have studied the alkaline hydrolysis mechanism for six different dimethylphosphate triesters. According to our calculations, we can conclude that for esters with poor leaving groups ( p K a lg > 8 ) the reaction occurs via a stepwise mechanism, whereas for good leaving groups, it occurs via a concerted mechanism. The attack of the hydroxide anion has the same characteristics for the six esters. So the stepwise or the concerted character of the hydrolysis mechanism is only due to the intrinsic characteristics of the leaving group. This point should be kept in mind when predicting the products of the hydrolysis reaction of phosphate triesters such as organophosphates.

Phosphate triester hydrolysis promoted by S 3–zinc(II) complexes with a bridged hydroxide: The crystal structure of TtiZn–OP(O)(OC 6H 4- p-NO 2) 2, Tti = hydrotris( N-xylyl-2-thioimidazolyl)borate

The bridged μ-hydroxo dinuclear four-co-ordinated zinc(II) complex 2, derived from hydrotris( N-xylyl-2-thioimidazolyl)borate cleaves the P–O bond in tris( p-nitrophenyl)phosphate to form a mixture of a monomeric phosphate diester complex 3 and phenoxo complex 4.

Phosphate Triester Hydrolysis Promoted by an N2S(thiolate)Zn Complex: Mechanistic Implications for the Metal-Dependent Reactivity of Peptide Deformylase

The zinc(II) complex (PATH)ZnOH, where PATH is an N2S(thiolate) ligand, has been investigated for its ability to promote the hydrolysis of the phosphate triester tris(4-nitrophenyl) phosphate (TNP). The hydrolysis of TNP was examined as a function of PATH-zinc(II) complex concentration, substrate concentration, and pH in a water/ethanol mixture (66:33 v/v) at 25 degrees C. The reaction is first order in both zinc(II) complex and substrate, and the second-order rate constants were derived from linear plots of the observed pseudo-first-order rate constants versus zinc complex concentration at different pH values. A pH-rate profile yielded a kinetic pK(a) of 8.52(5) for the zinc-bound water molecule and a pH-independent rate constant of 16.1(7) M(-1) s(-1). Temperature-dependent studies showed linear Eyring behavior, yielding the activation parameters DeltaH++ = 36.9(1) kJ mol(-1) and DeltaS++ = -106.7(4) J mol(-1) K(-1). Interpretation of the kinetic data leads to the conclusion that hydrolysis of TNP takes place through a hybrid mechanism, in which the metal center plays a dual role of providing a nucleophilic hydroxide and activating the substrate through a Lewis acid effect. The synthesis and structural characterization of the related nickel(II) and iron(II) complexes [(PATH)2Ni2]Br2 (2) and (PATH)2Fe2Cl2 (3) are also described. Taken together, these data suggest a possible explanation for the low reactivity of the zinc(II) form of peptide deformylase as compared to the iron(II) form.

Metallocyclodextrin Catalysts for Hydrolysis of Phosphate Triesters.

Abstract The copper complexes of 6A-(2-aminoethylamino)- and 6A-(3-aminopropylamino)-6A-deoxy-β-cyclodextrin catalyse the hydrolysis of 4-tert-butyl-2-nitrophenyl dimethyl phosphate, with kinc=3.1×10−2 and 2.3×10−2 s−1, and Kd=4.3×10−4 and 1.2×10−3 M, respectively, in 0.05 M pH 7.0 HEPES buffer at 298 K. This corresponds to rate accelerations of more than 95 000 and 70 000 times for reaction of the cyclodextrin-bound species.

Metallocyclodextrin catalysts for hydrolysis of phosphate triesters

The copper complexes of 6 A-(2-aminoethylamino)- and 6 A-(3-aminopropylamino)-6 A-deoxy-β-cyclodextrin catalyse the hydrolysis of 4- tert-butyl-2-nitrophenyl dimethyl phosphate, with k inc=3.1×10 −2 and 2.3×10 −2 s −1, and K d=4.3×10 −4 and 1.2×10 −3 M, respectively, in 0.05 M pH 7.0 HEPES buffer at 298 K. This corresponds to rate accelerations of more than 95 000 and 70 000 times for reaction of the cyclodextrin-bound species.

Catalysis of Phosphate Triester Hydrolysis by Micelles of Hexadecyltrimethylammonium anti-Pyruvaldehyde 1-Oximate

The hydrolysis reactions of 4-nitrophenyl diphenyl phosphate, 4-nitrophenyl di-4-tolyl phosphate, and diethyl 4-nitrophenyl phosphate (paraoxon) have been studied in hexadecyltrimethylammonium anti-pyruvaldehyde 1-oximate (C16TAOx) buffer solutions prepared by 1:2 mixing of hexadecyltrimethylammonium hydroxide with anti-pyruvaldehyde 1-oxime, thus allowing the avoidance of counterion inhibition effects observed when using conventional cationic surfactants. The reactions are strongly accelerated by the C16TAOx micelles, and the half-life for the persistent insecticide paraoxon is as low as 2 min at [C16TAOx] = 10-2 M. The data are discussed in terms of the pseudophase ion-exchange (PIE) model. However, this model is not sufficient to explain that the rate constants increase significantly when sodium oximate is added and that KCl and NaOAc salt effects exhibit S-shaped curves. Conductivity data suggest some minor variations in the degree of counterion association, β, but these variations are too small to ac...

Mutation of Arg-166 of alkaline phosphatase alters the thio effect but not the transition state for phosphoryl transfer. Implications for the interpretation of thio effects in reactions of phosphatases.

It has been suggested that the mechanism of alkaline phosphatase (AP) is associative, or triester-like, because phosphorothioate monoesters are hydrolyzed by AP approximately 10(2)-fold slower than phosphate monoesters. This "thio effect" is similar to that observed for the nonenzymatic hydrolysis of phosphate triesters, and is the inverse of that observed for the nonenzymatic hydrolysis of phosphate monoesters. The latter reactions proceed by loose, dissociative transition states, in contrast to reactions of triesters, which have tight, associative transition states. Wild-type alkaline phosphatase catalyzes the hydrolysis of p-nitrophenyl phosphate approximately 70 times faster than p-nitrophenyl phosphorothioate. In contrast, the R166A mutant alkaline phosphatase enzyme, in which the active site arginine at position 166 is replaced with an alanine, hydrolyzes p-nitrophenyl phosphate only about 3 times faster than p-nitrophenyl phosphorothioate. Despite this approximately 23-fold change in the magnitude of the thio effects, the magnitudes of Bronsted beta(lg) for the native AP (-0.77 +/- 0.09) and the R166A mutant (-0.78 +/- 0. 06) are the same. The identical values for the beta(lg) indicate that the transition states are similar for the reactions catalyzed by the wild-type and the R166A mutant enzymes. The fact that a significant change in the thio effect is not accompanied by a change in the beta(lg) indicates that the thio effect is not a reliable reporter for the transition state of the enzymatic phosphoryl transfer reaction. This result has important implications for the interpretation of thio effects in enzymatic reactions.

Catalytic hydrolysis of phosphate triesters by lanthanide(III) cryptate (2.2.1) complexes

Lanthanide(III) cryptate (2.2.1) chlorides [Ln(2.2.1)Cl3; Ln = La, Ce, Eu] are effective in catalysing the hydrolysis of 4-nitrophenyl diphenyl phosphate. Kinetic studies reveal that the europium(III)(2.2.1) chloride catalyses the hydrolysis efficiently (k= 1.8 × 10–2 s–1 at 1.6 mmol dm–3, turnover number = 12 at pH 9.00 and 25 °C). The reactivity of the cerium(III) complex is enhanced by the presence of molecular oxygen. Analysis of the products of the hydrolysis shows that the selectivity toward yielding 4-nitrophenol against phenol is unusually high (ratio = 17 : 1).

Antibody‐Catalyzed Phosphate Triester Hydrolysis

Not geometric but electrostatic features of the transition state serve as a paradigm for the design of antibodies that catalyze the hydrolysis of phosphate triesters. Thus, an efficient catalytic antibody was obtained with the dipolar amine oxide 1 as hapten. Potential applications of such antibodies include activation of prodrugs, disposal of insecticides, and counteraction of the toxicity of chemical warfare agents.

Convergent Functional Groups. 16. Hydrolysis of Phosphate Triesters by a Novel Cleft. Influence of Binding on Overall Rate Acceleration

Convergent Functional Groups. 16. Hydrolysis of Phosphate Triesters by a Novel Cleft. Influence of Binding on Overall Rate Acceleration

Cu II—diamine complex catalyzed hydrolysis of phosphate triesters adsorbed on strong-base ion exchange resins. 31P NMR relaxation measurements

The Cu II—diamine complexes, (bipy)CuSO 4 and (tmen)CuSO 4, catalyze the hydrolysis of p-nitrophenyl diphenyl phosphate (PNDP) adsorbed on a strong-base ion exchange resin. Turnover is observed. The major hydrolysis products are diphenyl phosphate, p-nitrophenyl phenyl phosphate, and the ethanolysis product ethyl diphenyl phosphate (EDPP) which are observed in similar amounts in both the presence and absence of the Cu II—diamine catalysts. The apparent bimolecular rate constants found for the (bipy) CuSO 4 and (tmen)CuSO 4 catalysts are 0.023 and 0.024 M −1 s −1, respectively. CuSO 4 is inactive as a catalyst. 31P MAS NMR relaxation measurements of the stable EDPP product reveal that the Cu II—diamine complexes greatly enhance T 1 relaxation, whereas CuSO 4 has only minimal effect. These results are consistent with the complexation of neutral phosphorus esters by the Cu II—diamine catalysts. 31P T 1 measurements of hydrolytically-stable dimethyl methylphosphonate (DMMP) in water solutions of Cu 2+, (tmen)Cu 2+, and Mn 2+ suggest that DMMP exchanges rapidly between inner-sphere and outer-sphere complexes in a nearly identical manner with each of these paramagnetic species.

ChemInform Abstract: Hydrolysis of Phosphate Triesters with Copper(II) Catalysts.

ChemInformVolume 20, Issue 38 Preparative Organic Chemistry ChemInform Abstract: Hydrolysis of Phosphate Triesters with Copper(II) Catalysts. J. R. MORROW, J. R. MORROW Dep. Chem., Univ. Calif. San Diego, La Jolla, CA 92093, USASearch for more papers by this authorW. C. TROGLER, W. C. TROGLER Dep. Chem., Univ. Calif. San Diego, La Jolla, CA 92093, USASearch for more papers by this author J. R. MORROW, J. R. MORROW Dep. Chem., Univ. Calif. San Diego, La Jolla, CA 92093, USASearch for more papers by this authorW. C. TROGLER, W. C. TROGLER Dep. Chem., Univ. Calif. San Diego, La Jolla, CA 92093, USASearch for more papers by this author First published: September 19, 1989 https://doi.org/10.1002/chin.198938093Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume20, Issue38September 19, 1989 RelatedInformation

Hydrolysis of phosphate triesters with copper(II) catalysts

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrolysis of phosphate triesters with copper(II) catalystsJanet R. Morrow and William C. TroglerCite this: Inorg. Chem. 1989, 28, 12, 2330–2333Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://doi.org/10.1021/ic00311a017RIGHTS & PERMISSIONSArticle Views379Altmetric-Citations47LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (483 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts