Zn(II) complexes of 1-oxa-4,7,10-triazacyclododecane (12[ane]N3O), 1,5,9-triazacyclododecane (12(ane]N3), and 1-hydroxyethyl-1,4,7-triazacyclononane (9[ane]N30H) promote cleavage of the RNA analogue, 2-hydroxypropyl4-nitrophenyl phosphate (HpPNP) at pH 8.0, I = 0.10 M (NaCl), 25 degrees C with second-order rate constants of 8.9 x 10(-3), 9.0 X 10(-3), and 3.3 x 10(-3) M-1 s(-1), respectively. Cleavage of HpPNP by these catalysts is inhibited by uridine with inhibition constants (K-i) of 1.2, 0.46, and 45 mM, respectively, under these conditions. Binding constants derived from these inhibition constants are 2-200-fold larger than those for binding of related Zn(II) complexes to phosphate diesters under similar conditions, suggesting that uridine sequences in RNA will inhibit Zn(II)-catalyzed cleavage by competing with phosphate diester binding sites. Further studies are carried out that utilize pH-potentiometric titrations to monitor uridine binding to five Zn(II) macrocyclic complexes in aqueous solution at 25 degrees C, / = 0.10 M (NaCl). The data are consistent with binding of the Zn(II) complexes to the N3-deprotonated form of uridine to give log K-U values of 5.29, 4.57, 4.56, 3.47, and 2.65 for the Zn(II) complexes of 12[ane]N3, 12[ane]N4, 12[ane]N30, 15[ane]N302, and g[ane]N30H, respectively (1 2[ane]N4 = 1,4,7,1 0-tetraazacyclododecane, 15[ane]N302 = 1,4-dioxa-7,10,13-triazacyclopentadecane). For the five Zn(II) complexes studied, there is a linear relationship between uridine anion binding constants and hydroxide binding constants.