Mechanism of Action of 3',5'-Cyclic Adenosine Monophosphate: A Study of Four- and Five-Coordinated Phosphorus Compounds, Modelling the Activated State of cAMP

摘要

The thesis describes experimental investigations on the structural properties of cAMP-derived five-coordinated phosphorus P(sup V) intermediates. These intermediates, with a trigonal bipyramidal geometry (TBP), are presumed to be formed during the interaction between cAMP and enzymes like phosphodiesterases and protein kinases. This assumption, based on quantum chemical CNDO/2 calculations, was first proposed by van Ool and Buck in 1982. They predicted that the 3',5'-dioxaphosphorinane ring prefered the diequatorial (e,e) location to the equatorial-axial (e,a) orientation in the P(sup V)-TBP. The results of chapters 2, 3, and 4, mainly based on (1)H-, (13)C-, and (31)P-NMR spectroscopy, show that both an (e,a) and an (e,e) orientation of the six-membered ring in P(sup V)-TBPs is possible. The study therefore has contributed to the insight of the dynamics of P(sup V)-TBPs, modelling the activated state of cAMP.