Theoretical Calculations on the Geometric Destabilization of 3’,5'- and 2’,3'-Cyclic Nucleotides

Frederick J. Marsh, Paul Weiner, Peter A. KoIlman, George L. Kenyon, John E. Douglas, John A. Gerlt

Research output: Contribution to journalArticle

Abstract

We present molecular mechanics and ab initio quantum mechanical calculations on some cyclic nucleotides and analogues with the goal of accounting for the unusually exothermic heats of hydrolysis of the six membered ring containing phosphodiester, 3’,5'-cyclic adenosine monophosphate (AMP), and of the five membered ring containing phosphodiester, 2’,3'-cyclic AMP. We attribute the greater exothermicity for hydrolysis of 3’,5'-cyclic AMP and the corresponding simple model-compounds relative to that for trimethylene phosphate (8 kcal/mol) to the following effects: (1) the trans ring fusion in 3’,5'-cyclic AMP, which leads to 4-5 kcal/mol of strain energy in this molecule, and (2) the presence in the 3’,5'-cyclic nucleotide of an unfavorable O-C-C-O interaction which is relieved upon phosphate ring cleavage. This second interaction, which is solvent dependent, can account for about 1 -2 kcal/mol of the difference in hydrolysis energy. (3) This leaves approximately 1-2 kcal/mol unaccounted for, and this may arise from differential solvation energies of the reactant and product. Our calculations overestimate the exothermicity of hydrolysis of the five membered ring containing phosphodiester, 2’,3'-cyclic AMP, but find, in agreement with experiment, that its exothermicity is much closer to the simple model phosphodiester, ethylene phosphate, than found in the corresponding six membered ring phosphodiesters.

Original languageEnglish (US)
Pages (from-to)1660-1665
Number of pages6
JournalJournal of the American Chemical Society
Volume102
Issue number5
DOIs
StatePublished - Feb 1980
Externally publishedYes

Fingerprint

Cyclic Nucleotides
Cyclic AMP
hydrolysis
Hydrolysis
Phosphates
phosphate
energy
Molecular mechanics
Solvation
Strain energy
ethylene
cleavage
mechanics
Mechanics
Fusion reactions
Ethylene
Hot Temperature
Molecules
calculation
experiment

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Theoretical Calculations on the Geometric Destabilization of 3’,5'- and 2’,3'-Cyclic Nucleotides. / Marsh, Frederick J.; Weiner, Paul; KoIlman, Peter A.; Kenyon, George L.; Douglas, John E.; Gerlt, John A.

In: Journal of the American Chemical Society, Vol. 102, No. 5, 02.1980, p. 1660-1665.

Research output: Contribution to journalArticle

Marsh, Frederick J. ; Weiner, Paul ; KoIlman, Peter A. ; Kenyon, George L. ; Douglas, John E. ; Gerlt, John A. / Theoretical Calculations on the Geometric Destabilization of 3’,5'- and 2’,3'-Cyclic Nucleotides. In: Journal of the American Chemical Society. 1980 ; Vol. 102, No. 5. pp. 1660-1665.
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