Molecular design of an acid?base cooperative catalyst for RNA cleavage based on a dizinc complex

Abstract
The effects of donor groups of dizinc complexes, formed from a 2:1 mixture of Zn(II) and a dinucleating ligand, on adenylyl(3′-5′)adenosine (ApA) cleavage have been studied. Two dinucleating ligands were used: one had two 2-pyridylmethyl and two 2-hydroxyethyl moieties on the 1,3-diamino-2-propanol linker moiety (2), and the other had two 2-pyridylmethyl and two carboxymethyl moieties on the 1,3-diamino-2-propanol linker moiety (3 2−). The dizinc complex with 2 [(Zn2+)2-2] showed higher activities toward ApA cleavage than the dizinc complex using an analogous dinucleating ligand having four 2-pyridylmethyl donor moieties [(Zn2+)2-1] at pH 5–8. The former showed a bell-shaped pH–rate constant profile, whereas the latter showed a sigmoidal pattern. The differences in the pH–rate constant profile are attributable to the various distributions of the monohydroxo-dizinc species, i.e. dideprotonated species, which are responsible for ApA cleavage. The monohydroxo species of (Zn2+)2-2 has two acidic protons, which are not present in the corresponding monohydroxo species of (Zn2+)2-1. The existence of both intracomplex acid (ROH or H2O) and base catalysts (RO− or OH−) in (Zn2+)2-2 can explain its higher activity toward ApA cleavage than that of (Zn2+)2-1. In contrast, (Zn2+)2-3 2− showed lower activity toward ApA cleavage at pH 7.0, which can be ascribed to the absence of the monohydroxo-dizinc species under these conditions.