Open AccessNucleophilic substitution at di- and triphosphates: leaving group ability of phosphate versus diphosphate
Author(s) -
Bas van Beek,
Marc A. van Bochove,
Trevor A. Hamlin,
F. Matthias Bickelhaupt
Publication year - 2019
Publication title -
electronic structure
Language(s) - English
Resource type - Journals
ISSN - 2516-1075
DOI - 10.1088/2516-1075/ab0af3
Subject(s) - chemistry , hydrolysis , atp hydrolysis , decomposition , adenosine triphosphate , leaving group , moiety , nucleotide , nucleophile , density functional theory , medicinal chemistry , phosphate , stereochemistry , enzyme , computational chemistry , biochemistry , organic chemistry , catalysis , atpase , gene
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 S N 2@P-induced hydrolysis, which drives uphill biochemical processes, such as, DNA replication. To this end, we have investigated the S N 2@P-induced hydrolysis of triphosphate (PPP) versus that of diphosphate (PP) using density functional theory (DFT) at COSMO(H 2 O)-ZORA-OLYP/TZ2P. We find that S N 2@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 Mg 2+ 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 P α –O leaving group bond.