Conformational transmission in pentacoordinated phosphorus systems, modelling the activated state of cyclic AMP

The proposed activated state of cyclic adenosine 3′,5′‐monophosphate (cAMP) is modelled by two nucleoside cyclic 3 ′,5 ′ P v ‐TBP compounds 3 and 4 . The reason for the design of compound 3 , in which a probe fragment (OCH 2 CH 2 OCH 3 group) is linked to phosphorus, was reflected in a conformational transmission effect, which occurs when the probe is located in the axis of a P v ‐TBP. This means that the six‐membered 3′5′‐dioxaphosphorinane ring predominantly remains in a diequatorial (e,e) orientation. In the absence of conformational transmission, as in compound 4 , the 3′,5′‐dioxaphosphorinane ring favors an equatorial‐axial (e,a) orientation. From this we conclude that the occurrence of conformational transmission can stabilize the (e,e) orientation of the 3′,5′‐ring. This can be of relevance to the activation of protein kinase by cAMP. In order to obtain more structural information from 3 and 4 , we performed MNDO calculations on the models 8–10 . These calculations revealed that the (e,e) orientation of the 3′,5′‐ring is destabilized by 3–4 kcal/mol compared to the (e,a) orientation. For the (e,a) geometry, the 3′,5′‐ring adopts a twist conformation, whereas the (e,e) orientated 3′,5′‐ring shows a half‐chair geometry.