Base moiety selectivity in cleavage of short oligoribonucleotides by di- and tri-nuclear Zn(II) complexes of azacrown-derived ligands.

Cleavage of 6-mer oligoribonucleotides by the dinuclear Zn2+ complex of 1,3-bis[(1,5,9-triazacyclododecan-3-yl)oxymethyl]benzene (L1) and the trinuclear Zn2+ complex of 1,3,5-tris[(1,5,9-triazacyclododecan-3-yl)oxymethyl]benzene (L3) has been studied. The dinuclear complex cleaves at sufficiently low concentrations ([(Zn2+)2L1] < or = 0.1 mmol L(-1)) the 5'NpU3' and 5'UpN3' bonds (N = G, C, A) much more readily than the other phosphodiester bonds, but leaves the 5'UpU3' site intact. The trinuclear (Zn2+)3L3 complex, in turn, cleaves the 5'UpU3' bond more readily than any other linkages, even faster than the 5'NpU3' and 5'UpN3' sites. Somewhat unexpectedly, the 5'UpNpU3' site is cleaved only slowly by both the di- and tri-nuclear complex. The base-moiety selectivity remains qualitatively similar, though slightly less pronounced, when the hexanucleotides are closed to hairpin loops by three additional CG-pairs of 2'-O-methylribonucleotides. Phosphodiester bonds within a double helical stem are not cleaved, not even the 5'UpU3' sites. Guanine base also becomes recognized by (Zn2+)2L1 and (Zn2+)3L3, but the affinity to G is clearly lower than to U. The trinuclear cleaving agent, however, cleaves the 5'GpG3' bond only 35% less readily than the 5'UpU3' bond.