Conformational Study of Cyclic and Acyclic Phosphate Esters. CNDO/2 Calculations of Angle Strain and Torsional Strain

Angle strain and torsional strain energies were calculated using the CNDO/2 LCAO-MO method for various geometries of dimethyl phosphate monoanion and compared with energies for 2′,3′-cyclic ribose phosphate and 3′-cyclic ribose phosphate. While the calculations fail to identify the source of the strain energy in the 3′,5′-cyclic six-membered ring nucleotides, they do indicate that a significant portion of the high heat of hydrolysis of the five-membered ring, 2′,3′-cyclic nucleotides is associated with relief of torsional strain and that preferred torsional conformations of acyclic esters are strongly coupled to the RO-P-OR bond angles. This coupling of ester, O-P-O bond angles, and torsional angles is also demonstrated by CNDO calculations on various geometries of trimethyl phosphate. Eclipsing of one of the phosphate ester bonds reduces the bond angle between the esterified oxygen atoms by ca. 5° and eclipsing of both ester bonds further reduces the bond angle by another 5°. These predictions of the CNDO calculations are shown to be supported by x-ray crystallographic structures of cyclic and acyclic, monoanionic, and neutral phosphate esters.