Nucleophilic substitution at di- and triphosphates: leaving group ability of phosphate versus diphosphate

Bas van Beek; Marc A van Bochove; Trevor A Hamlin; F Matthias Bickelhaupt

doi:10.1088/2516-1075/ab0af3

Nucleophilic substitution at di- and triphosphates: leaving group ability of phosphate versus diphosphate

Bas van Beek
, Marc A van Bochove
, Trevor A Hamlin
, F Matthias Bickelhaupt

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Adenosine triphosphate (ATP) is the universal energy carrier in biochemical processes. Herein, we aim for a better understanding of the origin of the high-energy content of the triphosphate moiety involved, the influence of various physicochemical factors thereon, and implication for the actual SN2@P-induced hydrolysis, which drives uphill biochemical processes, such as, DNA replication. To this end, we have investigated the SN2@P-induced hydrolysis of triphosphate (PPP) versus that of diphosphate (PP) using density functional theory (DFT) at COSMO(H2O)-ZORA-OLYP/TZ2P. We find that SN2@P-induced hydrolysis of PPP is favored over that of PP, both kinetically and thermodynamically. The energetic advantage of PPP over PP is slightly diminished by the coordination of Mg2+ counterions. Our activation strain and energy decomposition analyses reveal that the activation barrier for PPP hydrolysis is lower compared to that for PP due to a weaker Pα–O leaving group bond.

Original language	English
Article number	024001
Pages (from-to)	1-10
Number of pages	10
Journal	Electronic Structure
Volume	1
Issue number	2
Early online date	8 May 2019
DOIs	https://doi.org/10.1088/2516-1075/ab0af3
Publication status	Published - Jun 2019

Funding

This work was supported by The Netherlands Organization for Scientific Research (NWO) through the Planetary and Exo-Planetary Science (PEPSci) program and the Dutch Astrochemistry Network (DAN). We thank SURFsara for use of the Lisa supercomputer.

Funders
Dutch Astrochemistry Network
Planetary and Exo-Planetary Science
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 7 Affordable and Clean Energy

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10.1088/2516-1075/ab0af3

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title = "Nucleophilic substitution at di- and triphosphates: leaving group ability of phosphate versus diphosphate",

abstract = "Adenosine triphosphate (ATP) is the universal energy carrier in biochemical processes. Herein, we aim for a better understanding of the origin of the high-energy content of the triphosphate moiety involved, the influence of various physicochemical factors thereon, and implication for the actual SN2@P-induced hydrolysis, which drives uphill biochemical processes, such as, DNA replication. To this end, we have investigated the SN2@P-induced hydrolysis of triphosphate (PPP) versus that of diphosphate (PP) using density functional theory (DFT) at COSMO(H2O)-ZORA-OLYP/TZ2P. We find that SN2@P-induced hydrolysis of PPP is favored over that of PP, both kinetically and thermodynamically. The energetic advantage of PPP over PP is slightly diminished by the coordination of Mg2+ counterions. Our activation strain and energy decomposition analyses reveal that the activation barrier for PPP hydrolysis is lower compared to that for PP due to a weaker Pα–O leaving group bond.",

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T1 - Nucleophilic substitution at di- and triphosphates: leaving group ability of phosphate versus diphosphate

AU - Beek, Bas van

AU - Bochove, Marc A van

AU - Hamlin, Trevor A

AU - Bickelhaupt, F Matthias

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N2 - Adenosine triphosphate (ATP) is the universal energy carrier in biochemical processes. Herein, we aim for a better understanding of the origin of the high-energy content of the triphosphate moiety involved, the influence of various physicochemical factors thereon, and implication for the actual SN2@P-induced hydrolysis, which drives uphill biochemical processes, such as, DNA replication. To this end, we have investigated the SN2@P-induced hydrolysis of triphosphate (PPP) versus that of diphosphate (PP) using density functional theory (DFT) at COSMO(H2O)-ZORA-OLYP/TZ2P. We find that SN2@P-induced hydrolysis of PPP is favored over that of PP, both kinetically and thermodynamically. The energetic advantage of PPP over PP is slightly diminished by the coordination of Mg2+ counterions. Our activation strain and energy decomposition analyses reveal that the activation barrier for PPP hydrolysis is lower compared to that for PP due to a weaker Pα–O leaving group bond.

AB - Adenosine triphosphate (ATP) is the universal energy carrier in biochemical processes. Herein, we aim for a better understanding of the origin of the high-energy content of the triphosphate moiety involved, the influence of various physicochemical factors thereon, and implication for the actual SN2@P-induced hydrolysis, which drives uphill biochemical processes, such as, DNA replication. To this end, we have investigated the SN2@P-induced hydrolysis of triphosphate (PPP) versus that of diphosphate (PP) using density functional theory (DFT) at COSMO(H2O)-ZORA-OLYP/TZ2P. We find that SN2@P-induced hydrolysis of PPP is favored over that of PP, both kinetically and thermodynamically. The energetic advantage of PPP over PP is slightly diminished by the coordination of Mg2+ counterions. Our activation strain and energy decomposition analyses reveal that the activation barrier for PPP hydrolysis is lower compared to that for PP due to a weaker Pα–O leaving group bond.

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Nucleophilic substitution at di- and triphosphates: leaving group ability of phosphate versus diphosphate

Abstract

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UN SDGs

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