CYCLIC PENTAOXYPHOSPHORANES AS MODELS FOR cAMP ACTION. AN AB INITIO APPROACH

Abstract

Ab inirio molecular orbital calculations on monocyclic pentaoxyphosphorane molecules as model states in cyclic AMP action are carried out. Five-membered-ring systems are included for comparison. Minimum energy geometries in trigonal bipyramidal configurations that position the rings in axial–equatorial (a–e) sites are compared with those for diequatorial (e–e) ring locations. The models are made in-creasingly more complex approaching proposed intermediates in enzymatic hydrolysis of cAMP. These contain ribose rings trans-fused to the saturated six-membered ring of the pentacoordinated phosphorus state. All calculations show the e–e ring location to be higher in energy than the a–e ring arrangement. The computed energies and P–O bond lengths are compared with VT NMR activation energics for ligand exchange and with X-ray structural studies, respectively, on pentaoxyphosphoranes. The computations strongly support proposals for in-line enzymatic hydrolysis of cAMP with the ring positioned at a–e sites in a boat conformation.