The Zn(2+) complex of 1,4,7,10-tetraazacyclododecane as an artificial nucleobase.

{2-Deoxy-3-O-[2-cyanoethoxy(diisopropylamino)phosphino]-5-O-(4,4'-dimethoxytrityl)-α-D- erythro-pentofuranosyl}-N-{2-[4,7,10-tris(2,2,2-trifluoroacetyl)-1,4,7,10-tetraazacyclododecan-1- yl]ethyl}acetamide (1) was prepared and incorporated into a 2'-O-methyl oligoribonucleotide. The hybridization of this oligonucleotide with complementary 2'-O-methyl oligoribonucleotides incorporating one to five uracil bases opposite to the azacrown structure was studied in the absence and presence of Zn(2+). Introduction of Zn(2+) moderately stabilized the duplex with U-bulged targets.

Phosphorane intermediate vs. leaving group stabilization by intramolecular hydrogen bonding in the cleavage of trinucleoside monophosphates: implications for understanding catalysis by the large ribozymes.

Hydrolysis of 2',3'-O-methyleneadenosin-5'-yl 5'-O-methyluridin-2'-yl 5'-O-methyl-2'-trifluoroacetamido-2'-deoxyuridin-3'-yl phosphate (1b) has been followed by HPLC over a wide pH range to study the effects of potential hydrogen bonding interactions of the 2'-trifluoroacetamido function on the rate and product distribution of the reaction. At pH < 2, decomposition of 1b (and its 3',3',5'-isomer 1a) is first-order in hydronium-ion concentration and cleavage of the P-O3' bond of the 2'-trifluoroacetamido-modified nucleoside is slightly favored over cleavage of the P-O5' bond. Between pH 2 and 4, the overall hydrolysis is pH-independent and the P-O3' and P-O5' bonds are cleaved at comparable rates. At pH 5, the reaction becomes first-order in hydroxide-ion concentration, with P-O3' bond cleavage predominating. At 10 mmol L(-1) aqueous sodium hydroxide, no P-O5' bond cleavage is observed. Compared to the 2'-OH counterpart , a modest rate enhancement is observed over the entire pH range studied. The absence of P-O5' fission under alkaline conditions suggests hydrogen bond stabilization of the departing 3'-oxyanion by the neighboring 2'-trifluoroacetamido function.

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.