Catalytic Transesterification and Hydrolysis of RNA by Zinc(II) Complexes

The pseudo-first-order rate constants (k_obs) for transesterification of adenylyl-3; 5′-uridine 3′-monophosphate (ApUp) by Zn-([9]aneN₃)²⁺ (1), Zn([12]aneN₃)²⁺ (2), or Zn(cyclam)²⁺ (3) in water at 64 °C, pH = 7.6, follow the order 1 ≈ 2 > 3 ([9]aneN₃ = 1, 4, 7-triazacyclononane, [12]aneN₃ = 1, 5, 9-triazacyclododecane, cyclam = 1, 4, 8, 11-tetraazacyclotetradecane). Catalytic behavior is observed for transesterification of ApUp by 1; five turnovers of 1 were observed with no decrease in rate under conditions of excess ApUp. The pH-rate profile for the transesterification of ApUp by 1 is consistent with Zn([9]aneN₃)(OH)⁺ or its kinetic equivalent being the active catalyst. Transesterification of ApUp by 1 is inhibited at concentrations of 1 greater than 3.29 × 10^-4 M, where higher order complexes between 1 and ApUp may form. Consistent with these results, studies by Job's method indicate that a 1:1 complex between 1 and ApUp is the most reactive species. At 64 °C and pH = 7.6, 1 catalyzes the hydrolysis of 2′,3′-cAMP less rapidly than 1 catalyzes the transesterification of ApUp.