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-degrees-C, pH = 7.6, follow the order 1 almost-equal-to 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 x 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-degrees-C and pH = 7.6, 1 catalyzes the hydrolysis of 2',3'-cAMP less rapidly than 1 catalyzes the transesterification of ApUp.