Modeling the Alkaline Hydrolysis of Diaryl Sulfate Diesters : A Mechanistic Study
Szeler, Klaudia ; Williams, Nicholas H ; Hengge, Alvan C and Kamerlin, Shina C L LU
(2020)
In The Journal of Organic Chemistry
85(10).
p.6489-6497
- Abstract
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... (More)
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.
(Less)
- author
- Szeler, Klaudia
; Williams, Nicholas H
; Hengge, Alvan C
and Kamerlin, Shina C L
LU
- publishing date
- 2020-05-15
- type
- Contribution to journal
- publication status
- published
- in
- The Journal of Organic Chemistry
- volume
- 85
- issue
- 10
- pages
- 9 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:32309943
- scopus:85087738773
- ISSN
- 1520-6904
- DOI
- 10.1021/acs.joc.0c00441
- language
- English
- LU publication?
- no
- id
- 6a1cede4-d70e-492a-ab5a-dd5a0617c61b
- date added to LUP
- 2025-01-11 19:43:49
- date last changed
- 2025-01-18 03:18:27
@article{6a1cede4-d70e-492a-ab5a-dd5a0617c61b,
abstract = {{<p>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.</p>}},
author = {{Szeler, Klaudia and Williams, Nicholas H and Hengge, Alvan C and Kamerlin, Shina C L}},
issn = {{1520-6904}},
language = {{eng}},
month = {{05}},
number = {{10}},
pages = {{6489--6497}},
publisher = {{The American Chemical Society (ACS)}},
series = {{The Journal of Organic Chemistry}},
title = {{Modeling the Alkaline Hydrolysis of Diaryl Sulfate Diesters : A Mechanistic Study}},
url = {{http://dx.doi.org/10.1021/acs.joc.0c00441}},
doi = {{10.1021/acs.joc.0c00441}},
volume = {{85}},
year = {{2020}},
}