Bell-Shaped pH−Rate Profile in a Reaction Involving a Pentacoordinated Phosphorus Intermediate

Kinetics of the nucleophilic monosubstitution of imidazole by p -nitrophenolate (PNP - ) in hexaimidazolylcyclotriphosphazene (2) in water: THF 4:1 (5.5 < pH < 7.5) at 24 °C have been studied. The reaction was followed by the disappearance of the PNP - under pseudo-first-order conditions using the initial-rate procedure. A constant excess of KCl is needed in order to avoid medium effects. A bell-shaped curve is obtained when the k obs values (obtained from the leveling or the extrapolation to zero of k obs vs [H 2 PO 4 - ] T plots) are plotted against the pH. From this plot, a kinetically determined p K a of 5.4 was obtained for 2 . From the same plot, a 5.7 L mol -1 s -1 value for the second-order rate constant for the nucleophilic PNP - attack to the protonated species of 2 was found. A two-step mechanism is proposed. The formed pentacoordinated intermediate cleaves to the ( p -nitrophenoxy)pentaimidazolyl)cyclotriphosphazene (3) in a general-acid-catalyzed reaction. As expected of the proposed mechanism, a change in the rate-limiting step is observed at pH > 7.0 when the [buffer] T increases and k obs becomes independent of [buffer]. The implications of the present results on the controversial mechanism of hydrolysis of RNA and derivatives are discussed.