Transesterification Of a Phosphate Diester By Divalent And Trivalent Metal Ions

The transesterification of the 2-(4-nitrophenyl phosphate) ester of propylene glycol (1) was promoted by La³⁺, Nd³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Yb³⁺, Lu³⁺, Pb²⁺, Zn²⁺, Cu²⁺, Ni²⁺, Co²⁺, Mn²⁺, Mg²⁺, and Ca²⁺ at 37°C in 0.01 M Hepes buffer (Y-(2-hydroxyethyOpiperazine-.- V’-ethanesulfonic acid), pH 6.85. The ability of metal ions to promote transesterification of 1, as measured by apparent-second-order rate constants, followed the order Tb³⁺> Gd³⁺> Yb³⁺> Eu³⁺> Nd³⁺> Pb²⁺> Lu³⁺> La³⁺» Cu²⁺> Zn²⁺» Co²⁺> Mn²⁺> Ni²⁺» Mg²⁺> Ca²⁺. The transesterification of 1 by La³⁺, Pb²⁺, Zn²⁺, Cu²⁺, Ni²⁺, Co²⁺, or Mn²⁺ exhibited saturation kinetics, consistent with the formation of a reactive metal ion complex with 1. Metal ion association constants (AO for formation of the metal-1 complex and a first-order catalytic rate constant (fccat) for decomposition of the metal-1 complex were determined for metal ions that showed saturation kinetics. K varied by only a factor of 5, whereas Lcat varied by a factor of 29. Transesterification of 1 bound to Pb²⁺, La³⁺, Cu²⁺, Zn²⁺, Co²⁺, Mn²⁺, or Ni²⁺ occurred 2.1 × 104, 1.4 × 104, 4.6 × 103, 3.6 × 103, 9.2 × 102, 7.7 × 102, or 7.7 × 102 times more rapidly, respectively, than the transesterification of free 1. Properties of metal ions that may affect their ability to promote transesterification of phosphate esters are discussed; these include the Lewis acidity of the metal ion, the formation of metal hydroxide complexes, metal ion radius, and stabilization of a hypervalent phosphorus(V) intermediate. These metal ion model studies are put in context with metal ion requirements in self-cleaving RNAs.