ArticleJournal of the American Chemical Society2016
The Competing Mechanisms of Phosphate Monoester Dianion Hydrolysis.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Protonation and magnesium ions shape the transition state diversity of phosphoanhydride hydrolysis in water.Nature communications · 2026Article
- Time-Resolved Crystallography Reveals the Mechanisms of GTP hydrolysis for N-RAS and the Oncogenic Mutants G12C, G12V and Q61L.bioRxiv : the preprint server for biology · 2025Article
- The phosphodiester dissociative hydrolysis of a DNA model promoted by metal dications.Journal of molecular modeling · 2024Article
- 5'-Chalcogen-Substituted Nucleoside Pyrophosphate and Phosphate Monoester Analogues: Preparation and Hydrolysis Studies.International journal of molecular sciences · 2022Article
- Computational Modelling of the Interactions Between Polyoxometalates and Biological Systems.Frontiers in chemistry · 2022Review
- New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes.Molecules (Basel, Switzerland) · 2021Review
- Mechanisms of a Cyclobutane-Fused Lactone Hydrolysis in Alkaline and Acidic Conditions.Molecules (Basel, Switzerland) · 2021Article
- What Does the Brønsted Slope Measure in the Phosphoryl Transfer Transition State?ACS catalysis · 2020Article
- Differences in the Nature of the Phosphoryl Transfer Transition State in Protein Phosphatase 1 and Alkaline Phosphatase: Insights from QM Cluster Models.The journal of physical chemistry. B · 2020Article
- Modeling the Alkaline Hydrolysis of Diaryl Sulfate Diesters: A Mechanistic Study.The Journal of organic chemistry · 2020Article
- Recent Advances in Understanding Biological GTP Hydrolysis through Molecular Simulation.ACS omega · 2020Review
- Examining the Mechanism of Phosphite Dehydrogenase with Quantum Mechanical/Molecular Mechanical Free Energy Simulations.Biochemistry · 2020Article
- Quantum Mechanical/Molecular Mechanical Analysis of the Catalytic Mechanism of Phosphoserine Phosphatase.Molecules (Basel, Switzerland) · 2018Article
- Theoretical investigation of the neutral hydrolysis of diethyl 4-nitrophenyl phosphate (paraoxon) in aqueous solution.Journal of molecular modeling · 2018Article
- Mineralization and cementing properties of bio-carbonate cement, bio-phosphate cement, and bio-carbonate/phosphate cement: a review.Environmental science and pollution research international · 2018Review
- Allostery in the dengue virus NS3 helicase: Insights into the NTPase cycle from molecular simulations.PLoS computational biology · 2018Article
- Substrate and Transition State Binding in Alkaline Phosphatase Analyzed by Computation of Oxygen Isotope Effects.Journal of the American Chemical Society · 2016Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Despite the numerous experimental and theoretical studies on phosphate monoester hydrolysis, significant questions remain concerning the mechanistic details of these biologically critical reactions. In the present work we construct a linear free energy relationship for phosphate monoester hydrolysis to explore the effect of modulating leaving group pKa on the competition between solvent- and substrate-assisted pathways for the hydrolysis of these compounds. Through detailed comparative electronic-structure studies of methyl phosphate and a series of substituted aryl phosphate monoesters, we demonstrate that the preferred mechanism is dependent on the nature of the leaving group. For good leaving groups, a strong preference is observed for a more dissociative solvent-assisted pathway. However, the energy difference between the two pathways gradually reduces as the leaving group pKa increases and creates mechanistic ambiguity for reactions involving relatively poor alkoxy leaving groups. Our calculations show that the transition-state structures vary smoothly across the range of pKas studied and that the pathways remain discrete mechanistic alternatives. Therefore, while not impossible, a biological catalyst would have to surmount a significantly higher activation barrier to facilitate a substrate-assisted pathway than for the solvent-assisted pathway when phosphate is bonded to good leaving groups. For poor leaving groups, this intrinsic preference disappears.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.