Hydrolysis Of Phosphate Esters Research Articles

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.

The Hydrolytic Activity of Copper(II) Complexes with 1,4,7-Triazacyclononane Derivatives for the Hydrolysis of Phosphate Diesters.

A set of substituted 1,4,7-triazacyclononane ligands was synthesised, including a wide series of novel derivatives bearing a thiazole or thiophene side group, with the potential to incorporate these derivatives into a polymeric material; some previously known/studied ligands were also synthesised for comparative purposes. The corresponding copper(II) complexes were prepared, and their ability to mediate the hydrolysis of phosphate ester bonds was studied via UV-Vis spectrophotometry, using bis(p-nitrophenyl)phosphate as a model substrate. Some of the prepared complexes showed a considerable enhancement of the phosphate ester hydrolysis in comparison with previously studied systems, which makes them some of the most effective complexes ever tested for this purpose. Therefore, these novel, potentially bifunctional systems could provide the possibility of creating new coating materials for medicinal devices that could prevent biofilm formation.

Zn(II)-complex-based hydrolytic nanozymes prepared by nanoprecipitation for the hydrolysis of carboxylic esters and methyl parathion

Zn(II)-complex-based nanozymes have been extensively used for the cleavage of carboxylic esters and phosphate esters. Cooperativity between neighboring Zn(II) complexes is of paramount importance for the development of Zn(II)-complex-based nanozymes with excellent efficiency. Here, we have developed a controllable synthetic strategy for the construction of Zn(II)-complex-based nanozymes by using the nanoprecipitation technique, which could bring Zn(II) complexes in close proximity and regulate their microenvironments. Linear copolymers containing di(2-picolyl)amine moieties were used for the preparation of Zn(II)-complex-based nanozymes by the coordination between di(2-picolyl)amine and Zn(II) ion. These Zn(II)-complex-based nanozymes displayed excellent catalytic performance in the hydrolysis of carboxylic esters. Moreover, hydrophobic Fe3O4 nanoparticles could be incorporated into Zn(II)-complex-based nanozymes via the one-step nanoprecipitation approach, enabling the recovery of nanozymes by using a permanent magnet. Such nanozymes effectively catalyzed the hydrolysis of methyl parathion, which is highly resistant to spontaneous hydrolysis and is extremely hazardous. These nanozymes may find application in the hydrolysis of hazardous carboxylic esters and phosphate esters.

Kinetic Study of Solvent Effect on the Hydrolysis of Mono-3, 5-Dimethylaniline Phosphate

The hydrolysis of phosphate esters is one of the most fundamental chemical and biochemical reaction. The kinetic solvent effect on the hydrolysis of mono-3, 5-dimethylaniline phosphate has been studied in aqueous mixtures of varying compositions (0-40% v/v) of some protic and aprotic solvents at four different temperatures. The rate of reactions increases with increasing proportion of solvents. Activation parameters (Ea, ΔH≠, ΔG≠, -ΔS≠) have been evaluated. The significance of these parameters have been explained on the basis of solvent-solute interaction, solvent of the transition state of the medium.

Hydrolysis of ester phosphates mediated by a copper complex.

Phosphate ester hydrolysis is an important reaction that plays a major role in both enzymatic and non-enzymatic processes, including DNA and pesticide breaking. Although it is a widely studied reaction, the precise mechanistic details, especially for copper complexes, remain under discussion. To contribute to the debate, we present the catalyzed hydrolysis of phosphomono-, di- and tri-esters mediated by the [Cu(II)(1,10-phenanthroline)] complex. The reaction coordinates for several substrates were explored through the metadynamics formalism. Thus, we found that for mono- and di-substituted ester phosphates a concerted mechanism is observed, where a coordinated hydroxyl group attacks the phosphorus atom at the same side as the leaving group, along with a proton transfer. In contrast, tri-substituted phosphate remains coordinated with the metal, and the nucleophile acts independently following an addition-elimination process. That is, the metallic complex achieves a specific nucleophile-phosphate interaction that produces a concerted transition state in the phosphoester hydrolysis process.

Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm.

Alkaline phosphatase (ALP) is a ubiquitous membrane-bound glycoprotein capable of providing inorganic phosphate by catalyzing the hydrolysis of organic phosphate esters, or removing inorganic pyrophosphate that inhibits calcification. In humans, four forms of ALP cDNA have been cloned, among which tissue-nonspecific ALP (TNSALP) (TNSALP) is widely distributed in the liver, bone, and kidney, making it an important marker in clinical and basic research. Interestingly, TNSALP is highly expressed in juvenile cells, such as pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells (iPSCs)) and somatic stem cells (i.e., neuronal stem cells and bone marrow mesenchymal stem cells). Hypophosphatasia is a genetic disorder causing defects in bone and tooth development as well as neurogenesis. Mutations in the gene coding for TNSALP are thought to be responsible for the abnormalities, suggesting the essential role of TNSALP in these events. Moreover, a reverse-genetics-based study using mice revealed that TNSALP is important in bone and tooth development as well as neurogenesis. However, little is known about the role of TNSALP in the maintenance and differentiation of juvenile cells. Recently, it was reported that cells enriched with TNSALP are more easily reprogrammed into iPSCs than those with less TNSALP. Furthermore, in bone marrow stem cells, ALP could function as a “signal regulator” deciding the fate of these cells. In this review, we summarize the properties of ALP and the background of ALP gene analysis and its manipulation, with a special focus on the potential role of TNSALP in the generation (and possibly maintenance) of juvenile cells.

Mechanistic Insights into Promoted Hydrolysis of Phosphoester Bonds by MoO2Cl2(DMF)2.

A phosphoester bond is a crucial structural block in biological systems, whose occurrence is regulated by phosphatases. Molybdenum compounds have been reported to be active in phosphate ester hydrolysis of model phosphates. Specifically, MoO2Cl2(DMF)2 is active in the hydrolysis of para-nitrophenyl phosphate (pNPP), leading to heteropolyoxometalate structures. We use density functional theory (DFT) to clarify the mechanism by which these species promote the hydrolysis of the phosphoester bond. The present calculations give insight into several key aspects of this reaction: (i) the speciation of this complex prior to interaction with the phosphate (DMF release, Mo-Cl hydrolysis, and pH influence on the speciation), (ii) the competition between phosphate addition and the molybdate nucleation process, (iii) and the mechanisms by which some plausible active species promote this hydrolysis in different conditions. We described thoroughly two different pathways depending on the nucleation possibilities of the molybdenum complex: one mononuclear mechanism, which is preferred in conditions in which very low complex concentrations are used, and another dinuclear mechanism, which is preferred at higher concentrations.

Alkaline Phosphatase Serum Level at Time of Diagnosis Is a Prognostic Marker in Patients with Hodgkin Lymphoma

BackgroundHodgkin lymphoma (HL) is a potentially curable lymphoma with distinct histology, biologic behavior, and clinical characteristics. It is among the neoplastic diseases that has the best long-term outcome after treatment. Cure rates approach 80-90%; however, 15-20% of patients will be resistant to therapy or relapse after treatment. International Prognostic Score (IPS) is The most widely utilized clinical index to assign risk in HL patients. Alkaline Phosphatase (ALP) comprises a group of enzymes that catalyze the hydrolysis of phosphate esters in an alkaline environment, generating an organic radical and inorganic phosphate .ALP presents in all human tissues, but it's highest concentrations are found in the liver, bones, kidneys and placenta. Elevated ALP serum levels was shown to be a bad prognostic factor in patient with metastatic colorectal and breast cancers.AimTo study the prognostic role of ALP serum level at time of diagnosis in HL patients.Methods109 patients diagnosed with HL between January 2004 to December 2016 were retrospectively reviewed at King Abdullah University Hospital (KAUH) . Clinical and laboratory data at time of diagnosis including gender, age, presenting symptoms, ALP level, Complete Blood Count (CBC), Lactate Dehydrogenase (LDH) level, pathological subtypes, CT and PET/CT scans were studied. All IPS 7 variables including: male sex, age >45 years, stage IV disease, hemoglobin (Hb) <10.5g/dl, white blood count (WBC) ≥ 15 × 109/L, lymphocyte count < 0.6 × 109/L or <8% of total WBC, and albumin < 40g/dL were recorded at time of diagnosis. Extranodal involvement was confirmed by tissue diagnosis. All our patients received the same ABVD treatment regimen. The optimal cut-off value for ALP level was obtained using the Receiver Operating Curve (ROC) with a determination of the sensitivity and specificity . We analyzed for associations between ALP serum level and patient characteristics. Data were assessed using the Kaplan-Meier method, and the log-rank test was utilized to compare survival time between the groups.ResultsThe median age at diagnosis was 31 years (Range = 18-89 years). 55% were males and 45% were females. Patient characteristics are summarized in the table. Median ALP serum level was 250 U/L (range , 88-1234) and the optimal cutoff value of ALP serum level for predicting overall survival (OS) was 219 U/L (Sensitivity 86.4% , Specificity 46.50%; area under the curve [AUC] value: 0.668, 95% confidence interval [CI] 0.548-0.778, P= 0.019). In univariate analysis, elevated ALP level was significantly associated with poorer OS (HR=4.21, 95% CI: 1.24-14.26 , P-value=0.012). Mean survival time for patients with high ALP level was 11.68 years , compared to patients with low ALP level 10.96 years. In multivariate analysis ,there was significant association between high serum ALP level and IPS (P-value<.001), low Hb level (P-value=.002) , low Albumin level (P-value=.001) and high LDH level (.019). Involvement of more than one extra-nodal site was associated with poorer OS (HR=4.35 ,95% CI: 1.23-15.34 , P-value=0.022). There was no significant association between high ALP level and bone involvement (P-value=.072) ,liver involvement (P-value=.12) and HL subtype (P-value=.45).SummaryALP serum level may be a useful and un-expensive prognostic marker in patient with HL. The OS rate in patient with high ALP serum level at time of diagnosis is significantly lower than OS rate in patients with low serum levels. High ALP level is significantly associated with high IPS score , more than one EN site involvement , low Hb level , low albumin level and high LDH level. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Measurement of Nucleotide Hydrolysis Using Fluorescent Biosensors for Phosphate.

Assays for the detection of inorganic phosphate (Pi) are widely used to measure the activity of nucleotide hydrolyzing enzymes, such as ATPases and GTPases. The fluorescent biosensors for Pi, described here, are based on fluorescently labeled versions of E. coli phosphate-binding protein (PBP), which translates Pi binding into a large change in fluorescence intensity. In comparison with other Pi-detection systems, these biosensors are characterized by a high sensitivity (sub-micromolar Pi concentrations) and high time resolution (tens of milliseconds), and they are therefore particularly well suited for measurements of phosphate ester hydrolysis in real time. In this chapter, it is described how the Pi biosensors can be used to measure kinetics of ATPase and GTPase reactions, both under steady state and pre-steady state conditions. An example protocol is given for determining steady state kinetic parameters, Km and kcat, of the ATP-dependent chromatin remodeler Chd1, in a plate reader format. In addition, the measurement of Pi release kinetics under pre-steady state conditions is described, including a detailed experimental procedure for a singleturnover measurement of ATP hydrolysis by the ABC-type ATPase SufBC using rapid mixing.

What Does the Brønsted Slope Measure in the Phosphoryl Transfer Transition State?

The structural and energetic features of phosphate and phosphonate hydrolysis in Protein Phosphatase-1 (PP1) and water are studied using quantum mechanical (QM) cluster models. The calculations are able to reproduce observed kinetic isotope effects and capture several key trends in the experimental Brønsted plots: the values are rather different for phosphate and phosphonate ester hydrolysis in solution but are similar in PP1. Detailed analyses of structure, charge distribution and bond order of computed transition states support the general conclusion from experimental study that phosphoryl transfer transition states are different for the two classes of substrates in solution but similar in PP1. On the other hand, the microscopic models also highlight notable differences between the phosphate and phosphonate transition states, which are manifested in not only structure but also kinetic isotope effects. Overall, we find that while generally correlates with the partial charge on leaving group oxygen and the fractional bond order of the breaking P- bond, the precise mapping between and P- bond order in the transition state is difficult due largely to the cross talk between breaking and forming P-O bonds. Therefore, further supporting previous analyses of limitations of free energy relations, our results suggest that while free energy relation is a valuable tool for probing the nature of transition state, a quantitative mapping of and values to structure or charge in the transition state should be conducted with great care.

Recent Advances in Heterogeneous Catalytic Systems Containing Metal Ions for Phosphate Ester Hydrolysis.

Organophosphates are a class of organic compounds that are important for living organisms, forming the building blocks for DNA, RNA, and some essential cofactors. Furthermore, non-natural organophosphates are widely used in industrial applications, including as pesticides; in laundry detergents; and, unfortunately, as chemical weapons agents. In some cases, the natural degradation of organophosphates can take thousands of years; this longevity creates problems associated with handling and the storage of waste generated by such phosphate esters, in particular. Efforts to develop new catalysts for the cleavage of phosphate esters have progressed in recent decades, mainly in the area of homogeneous catalysis. In contrast, the development of heterogeneous catalysts for the hydrolysis of organophosphates has not been as prominent. Herein, examples of heterogeneous systems are described and the importance of the development of heterogeneous catalysts applicable to organophosphate hydrolysis is highlighted, shedding light on recent advances related to different solid matrices that have been employed.

Efficient Catalysis of Phosphate Ester Hydrolysis by Bare Silica

This work reports the catalysis of bare silica materials (MCM-41, SBA-15, and silica gel) for the complete hydrolyses of bis(2,4-nitrophenyl)phosphate (BDNPP) and bis(4-nitrophenyl)phosphate (BNPP)...

Over-processed meat and bone meal and phytase effects on broilers challenged with subclinical necrotic enteritis: Part 2. Inositol phosphate esters hydrolysis, intestinal permeability, hematology, jejunal gene expression and intestinal morphology.

This study investigated the hypothesis that feeding broilers over-processed meat and bone meal (MBM) would impair gut health in the absence of phytase and in turn, affect inositol phosphate (inositol x-phosphate, IPx: IP3, IP4, IP5 and IP6) ester hydrolysis, intestinal permeability, hematology, jejunal gene expression and intestinal morphology during necrotic enteritis (NE). Ross 308 male broilers (n = 768) were assigned to one of 8 dietary treatments in a 2 × 2 × 2 factorial arrangement, with 6 replicate pens per diet and 16 birds per pen in a completely randomized design. Factors were: NE challenge (no or yes), phytase level (500 or 5,000 FTU/kg) and MBM processing (as-received or over-processed). For the NE challenge, half of the birds were challenged with field strains of Eimeria spp. on d 9 and 108 CFU/mL of Clostridium perfringens strain EHE-NE18 on d 14 and 15. A 3-way challenge, phytase and MBM processing interaction was detected for IP5 (P < 0.05) and IP6 (P < 0.05) levels in the ileum. Birds fed low phytase had increased IP5 and IP6 in unchallenged birds only when diets contained over-processed MBM. Challenge with NE increased intestinal permeability as measured by serum fluorescein isothiocyanate dextran (FITC-d; P < 0.001), increased white blood cells (WBC; P < 0.001), decreased mean corpuscular volume (MCV; P < 0.001) and mean corpuscular hemoglobin (MCH; P < 0.05), and decreased crypt-to-villi ratio (P < 0.05). The over-processed MBM reduced the villi-to-crypt ratio (P < 0.05). A 3-way challenge × phytase × MBM processing interaction was detected for mucin 2 (MUC-2) expression (P < 0.05) where only in unchallenged birds fed over-processed MBM did high phytase reduce MUC-2 expression. A lower expression of aminopeptidase N (APN; P < 0.001) and vitamin D receptor (VDR; P < 0.001) were recorded in NE challenged birds. In conclusion, NE has a negative impact on the gut and hematology of broilers, but its effect on phytate hydrolysis is minimal.

Synthesis, crystal structure, phosphate hydrolysis activity and antibacterial activity of macrocyclic dinuclear Zn(II) complex with benzyl pendant-arms

A new macrocyclic dinuclear Zn(II) complex is synthesized by the cyclocondensation between 3,3’-(ethane-1,2-diylbis (benzylazanediyl))bis(methylene) bis (2-hydroxy-5-methyl-benzaldehyde) and 1,3-diaminopropane and the subsequent with zinc salts. The as-prepared complex is characterized by elemental analysis, FT-IR, ES-MS and single crystal X-ray diffraction. The complex consists of one independent molecular unit of [Zn2(μ-OAC)L]+ ClO4− and two water molecules with one on a symmetry element. Four of these units collectively form two pairs of dinuclear complex units of [Zn2(μ-OAc)L]+ with one unit sharing two perchlorate ions and one water molecule and the other unit sharing two perchlorate ions and one symmetry equivalent water molecule. Each zinc(II) ion exhibits a slightly distorted square pyramidal geometry. Two Zn atoms are bridged by two oxygen atoms of an acetate anion and two phenolic O atoms. The Zn–Zn distance is 2.951 Å. An ordered two-dimensional network is formed by weak intermolecular interactions in the crystal structure of the complex. The phosphate ester hydrolysis activity and the antibacterial activity of the complex are studied. The results showed that the synthesized complex has an efficient catalytic activity of phosphoester bond cleavage and the potential to inhibit the growth of E. coli. The optimum catalytic rate constant (kcat) at pH 7.8 for the hydrolysis of 4-nitrophenyl phosphate disodium salt hexahydrate (pNPP) by the synthesized complex is 2.98 × 10−4 s−1, and 105 times faster than that the spontaneous hydrolysis of the phosphate monoester.

Modeling the Alkaline Hydrolysis of Diaryl Sulfate Diesters: A Mechanistic Study.

Phosphate and sulfate esters have important roles in regulating cellular processes. However, while there has been substantial experimental and computational investigation of the mechanisms and the transition states involved in phosphate ester hydrolysis, there is far less work on sulfate ester hydrolysis. Here, we report a detailed computational study of the alkaline hydrolysis of diaryl sulfate diesters, using different DFT functionals as well as mixed implicit/explicit solvation with varying numbers of explicit water molecules. We consider the impact of the computational model on computed linear free-energy relationships (LFER) and the nature of the transition states (TS) involved. We obtain good qualitative agreement with experimental LFER data when using a pure implicit solvent model and excellent agreement with experimental kinetic isotope effects for all models used. Our calculations suggest that sulfate diester hydrolysis proceeds through loose transition states, with minimal bond formation to the nucleophile and bond cleavage to the leaving group already initiated. Comparison to prior work indicates that these TS are similar in nature to those for the alkaline hydrolysis of neutral arylsulfonate monoesters or charged phosphate diesters and fluorophosphates. Obtaining more detailed insights into the transition states involved assists in understanding the selectivity of enzymes that hydrolyze these reactions.

Development, synthesis and biological investigation of a novel class of potent PC-PLC inhibitors

Phospholipases are enzymes that are involved in the hydrolysis of acyl and phosphate esters of phospholipids, generating secondary messengers that have implications in various cellular processes including proliferation, differentiation and motility. As such inhibitors of phospholipases have been widely studied for their use as anti-cancer therapeutics. Phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in the progression of a number of cancer cell lines including aggressing triple-negative breast cancers. Most current studies on PC-PLC have utilised D609 as the standard inhibitor however it is known to have multiple failings, including poor stability in aqueous media. 2-Morpholinobenzoic acids were recently identified using vHTS as a potential class of lead compounds, with improvements over D609. In this work 129 analogues in this class were prepared and their PC-PLC inhibitory activity was assessed. It was found that the majority of these novel compounds had improved activity when compared to D609 with the most potent inhibitors completely inhibiting enzyme activity. It was determined that the best compound/s contained a morpholino and 2-substituted N-benzyl moieties with these findings explained using molecular modelling. The compounds reported here will allow for improved study of PC-PLC activity.

Fabrication of highly active phosphatase-like fluorescent cerium-doped carbon dots for in situ monitoring the hydrolysis of phosphate diesters.

Ce-Doped carbon dots (CeCDs) were fabricated via a one-step hydrothermal carbonization using Ce(NO3)3·6H2O and EDTA·2H2O as precursors, and various experimental techniques were employed to characterize the morphology, structure and composition of the as-obtained CeCDs. Using the disodium salt of bis(4-nitrophenyl)phosphate (BNPP) as a DNA model substrate, mimetic phosphatase activity toward phosphate ester hydrolysis cleavage was investigated. It was found that similar to the catalytic character of the natural enzyme, CeCDs as a hydrolase mimic can exhibit a good catalytic activity for promoting BNPP hydrolysis, in which metal Ce(iii) acts as a center for binding and activation of the metal-bound hydroxide complex as well as a source of nucleophilic metal hydroxides. Additionally, based on the Inner Filter Effect (IFE), fluorescence spectra can be used to monitor the hydrolysis of BNPP using CeCDs, which mimic phosphatase. Thus, the unique properties of the CeCD mimetic phosphatases as well as the IFE sensing strategy would provide an ideal platform to monitor the catalytic phosphate ester hydrolysis processes. Finally, to validate the availability of the established catalytic systems, the CeCDs were further applied for degradation of organophosphorus pesticide chlorpyrifos. The degradation efficiency was estimated to be a satisfactory value of 74.50%, exhibiting a potential application prospect for treatment of the pollutants in the soil and water.

A new macrocyclic heterobinuclear Cu(II)-Zn(II) complex: synthesis, crystal structure, phosphate hydrolysis, and DNA binding studies

A new macrocyclic heterobinuclear Cu(II)-Zn(II) complex was synthesized and characterized by elemental analysis, FT-IR, ES-MS, and single-crystal X-ray diffraction. Five-coordinate geometry for the new complex is proposed. The copper…zinc distance bridged by two phenolic oxygens and a acetate ligand is 2.9508 Å. The phosphate ester hydrolysis activity and the DNA binding ability of the complex were studied. The results showed that the present complex has an efficient catalytic activity of phosphoester bond cleavage. The catalytic rate constant kcat for the hydrolysis of 4-nitrophenyl phosphate disodium salt hexahydrate (pNPP) by the synthesized complex is 2.69 × 10−4 s−1 and 105 times faster than the spontaneous hydrolysis of the phosphate monoester. The complex shows a good binding ability to calf thymus (CT-DNA) and the corresponding binding constant is 1.9 × 105 M−1. The linear Stern-Volmer quenching constant obtained by the fluorescent spectroscopic is 6.3 × 104 M−1.

Mechanistic Studies of Homo- and Heterodinuclear Zinc Phosphoesterase Mimics: What Has Been Learned?

Phosphoesterases hydrolyze the phosphorus oxygen bond of phosphomono-, di- or triesters and are involved in various important biological processes. Carboxylate and/or hydroxido-bridged dizinc(II) sites are a widespread structural motif in this enzyme class. Much effort has been invested to unravel the mechanistic features that provide the enormous rate accelerations observed for enzymatic phosphate ester hydrolysis and much has been learned by using simple low-molecular-weight model systems for the biological dizinc(II) sites. This review summarizes the knowledge and mechanistic understanding of phosphoesterases that has been gained from biomimetic dizinc(II) complexes, showing the power as well as the limitations of model studies.

Metal-Assisted Hydrolysis Reactions Involving Lipids: A Review.

This report covers major advances in the use of metal ions and complexes to hydrolyze ester and phosphate ester lipid bonds. These metal-based Lewis acids have been investigated as catalysts to isolate fatty acids from biological sources, as probes to study phospholipid bilayer properties, as tools to examine signal transduction pathways, and as lead compounds toward the discovery of therapeutic agents. Metal ions that accelerate phosphate ester hydrolysis under mild conditions of temperature and pH may have the potential to mimic phospholipase activity in biochemical applications.