ArticleJournal of the American Chemical Society2015
Resolving apparent conflicts between theoretical and experimental models of phosphate monoester hydrolysis.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed.
- Critical structural perturbations of ribozyme active sites induced by 2'-O-methylation commonly used in structural studies.Nucleic acids research · 2026Article
- Hydrolysis mechanisms for A-series (Novichok) nerve agents at different pH V and computational simulant screening.RSC advances · 2026Article
- Article
- Prebiotic chemical reactivity in solution with quantum accuracy and microsecond sampling using neural network potentials.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Aqueous degradation of 6-APA by hydroxyl radical: a theoretical study.Journal of molecular modeling · 2023Article
- Origin of iodine preferential attack at sulfur in phosphorothioate and subsequent P-O or P-S bond dissociation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Computational Modelling of the Interactions Between Polyoxometalates and Biological Systems.Frontiers in chemistry · 2022Review
- Synthesis, Stability, and Kinetics of Hydrogen Sulfide Release of Dithiophosphates.Journal of agricultural and food chemistry · 2021Article
- 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
- Dual-Selective Catalysis in Dephosphorylation Tuned by HfACS central science · 2021Article
- Reactions of aryl dimethylphosphinothioate esters with anionic oxygen nucleophiles: transition state structure in 70% water-30% ethanol.RSC advances · 2021Article
- Biomolecular QM/MM Simulations: What Are Some of the "Burning Issues"?The journal of physical chemistry. B · 2021Article
- What Does the Brønsted Slope Measure in the Phosphoryl Transfer Transition State?ACS catalysis · 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
- Extensive free-energy simulations identify water as the base in nucleotide addition by DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Molecular Mechanism of ATP Hydrolysis in an ABC Transporter.ACS central science · 2018Article
- Mechanistic Insights on Human Phosphoglucomutase Revealed by Transition Path Sampling and Molecular Dynamics Calculations.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Understanding phosphoryl and sulfuryl transfer is central to many biochemical processes. However, despite decades of experimental and computational studies, a consensus concerning the precise mechanistic details of these reactions has yet to be reached. In this work we perform a detailed comparative theoretical study of the hydrolysis of p-nitrophenyl phosphate, methyl phosphate and p-nitrophenyl sulfate, all of which have served as key model systems for understanding phosphoryl and sulfuryl transfer reactions, respectively. We demonstrate the existence of energetically similar but mechanistically distinct possibilities for phosphate monoester hydrolysis. The calculated kinetic isotope effects for p-nitrophenyl phosphate provide a means to discriminate between substrate- and solvent-assisted pathways of phosphate monoester hydrolysis, and show that the solvent-assisted pathway dominates in solution. This preferred mechanism for p-nitrophenyl phosphate hydrolysis is difficult to find computationally due to the limitations of compressing multiple bonding changes onto a 2-dimensional energy surface. This problem is compounded by the need to include implicit solvation to at least microsolvate the system and stabilize the highly charged species. In contrast, methyl phosphate hydrolysis shows a preference for a substrate-assisted mechanism. For p-nitrophenyl sulfate hydrolysis there is only one viable reaction pathway, which is similar to the solvent-assisted pathway for phosphate hydrolysis, and the substrate-assisted pathway is not accessible. Overall, our results provide a unifying mechanistic framework that is consistent with the experimentally measured kinetic isotope effects and reconciles the discrepancies between theoretical and experimental models for these biochemically ubiquitous classes of reaction.
Indexed as
Identifiers
What OpenQuestion holds
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.