Hyperconjugation-mediated solvent effects in phosphoanhydride bonds

Jean C. Summerton, Jeffrey D. Evanseck, Michael Chapman

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Density functional theory and natural bond orbital analysis are used to explore the impact of solvent on hyperconjugation in methyl triphosphate, a model for "energy rich" phosphoanhydride bonds, such as found in ATP. As expected, dihedral rotation of a hydroxyl group vicinal to the phosphoanhydride bond reveals that the conformational dependence of the anomeric effect involves modulation of the orbital overlap between the donor and acceptor orbitals. However, a conformational independence was observed in the rotation of a solvent hydrogen bond. As one lone pair orbital rotates away from an optimal antiperiplanar orientation, the overall magnitude of the anomeric effect is compensated approximately by the other lone pair as it becomes more antiperiplanar. Furthermore, solvent modulation of the anomeric effect is not restricted to the antiperiplanar lone pair; hydrogen bonds involving gauche lone pairs also affect the anomeric interaction and the strength of the phosphoanhydride bond. Both gauche and anti solvent hydrogen bonds lengthen nonbridging O-P bonds, increasing the distance between donor and acceptor orbitals and decreasing orbital overlap, which leads to a reduction of the anomeric effect. Solvent effects are additive with greater reduction in the anomeric effect upon increasing water coordination. By controlling the coordination environment of substrates in an active site, kinases, phosphatases, and other enzymes important in metabolism and signaling may have the potential to modulate the stability of individual phosphoanhydride bonds through stereoelectronic effects.

Original languageEnglish (US)
Pages (from-to)10209-10217
Number of pages9
JournalJournal of Physical Chemistry A
Volume116
Issue number41
DOIs
StatePublished - Oct 18 2012

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Hydrogen bonds
orbitals
Modulation
hydrogen bonds
Phosphoric Monoester Hydrolases
Metabolism
Hydroxyl Radical
Density functional theory
modulation
Phosphotransferases
Adenosine Triphosphate
phosphatases
adenosine triphosphate
metabolism
Water
enzymes
Substrates
Enzymes
density functional theory
water

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

Cite this

Hyperconjugation-mediated solvent effects in phosphoanhydride bonds. / Summerton, Jean C.; Evanseck, Jeffrey D.; Chapman, Michael.

In: Journal of Physical Chemistry A, Vol. 116, No. 41, 18.10.2012, p. 10209-10217.

Research output: Contribution to journalArticle

Summerton, Jean C. ; Evanseck, Jeffrey D. ; Chapman, Michael. / Hyperconjugation-mediated solvent effects in phosphoanhydride bonds. In: Journal of Physical Chemistry A. 2012 ; Vol. 116, No. 41. pp. 10209-10217.
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