Zn2+ Complexes of Di‐ and Tri‐nucleating Azacrown Ligands as Base‐Moiety‐Selective Cleaving Agents of RNA 3′,5′‐Phosphodiester Bonds: Binding to Guanine Base

The ability of the dinuclear Zn2+ complex of 1,4‐bis[(1,5,9‐triazacyclododecan‐3‐yloxy)methyl]benzene (L1) to promote the cleavage of the phosphodiester bond of dinucleoside‐3′,5′‐monophosphates that contain a guanine base has been studied over a narrow pH range from pH 5.8 to 7.2 at 90 °C. Comparative measurements have been carried out by using the trinuclear Zn2+ complex of 1,3,5‐tris[(1,5,9‐triazacyclododecan‐3‐yloxy)methyl]benzene (L2) as a cleaving agent and guanylyl‐3′,5′‐guanosine (5′‐GpG‐3′) as a substrate. The strength of the interaction between the cleaving agent and the starting material has been elucidated by UV spectrophotometric titrations. The speciation and binding mode have been clarified by potentiometric titrations with hydrolytically stable 2′‐O‐methylguanylyl‐3′,5′‐guanosine and 1H NMR spectroscopic measurements with guanylyl‐3′,5′‐guanosine. The results show that the guanine base is able to serve as a site for anchoring for the Zn2+–azacrown moieties of the cleaving agents L1 and L2, analogously to uracil base. The interaction is, however, weaker than with the uracil base and, hence, only the 5′‐GpG‐3′ site (in addition to 5′‐GpU‐3′ and 5′‐UpG‐3′ sites) is able to markedly modulate the phosphodiester cleavage by the Zn2+ complexes of di‐ and trinucleating azacrown ligands containing an ether oxygen as a potential H‐bond‐acceptor site.