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

Abstract

The ability of the dinuclear Zn2+ complex of 1,4-bis[(1,5,9-triazacyclododecan-3-yloxy)methyl]benzene (L(1)) 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 degrees 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 (L(2)) 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 L(1) and L(2), 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.

(Un)suitability of the use of pH buffers in biological, biochemical and environmental studies and their interaction with metal ions – a review

“…These studies involve proteins with heme groups, [134][135][136] Zn-nger motifs, [137][138][139] metalloproteins 116,133,[140][141][142] and/or other complexing agents in solution. 81,[143][144][145] In fact, the concentrations of the compounds used, and most importantly the ratio of the buffer concentration to the complexing compound concentration in the medium, are within values that support the idea that no interference of the buffer occurs.…”

Guanidine‐Based Polymer Brushes Grafted onto Silica Nanoparticles as Efficient Artificial Phosphodiesterases

“…Reported data on the catalyzed cleavage of diribonucleoside monophosphates clearly indicate that catalytic efficiency depends, in a very critical way, on the identity of both nucleobases N and N′. In the case of cleavage promoted by di‐ and trinuclear metal complexes, the selectivity for some sequences have been ascribed to a preassociation mechanism, supported by spectroscopic analysis22c, d and kinetic data,22 in which the deprotonated amidic NH bond of a nucleobase serves as a site to anchor to a ligated Cu II or Zn II center in the catalyst. This explanation does not apply in the present case because of the absence of metal centers in the catalyst and the absence of any NH group in the most reactive sequence CpA.…”

Phosphodiester models for cleavage of nucleic acids

“…In contrast to these results, rate-enhancement by 27a is fairly insensitive to base composition: among five different 3,5-dinucleoside monophosphates studied, only a 3.5-fold difference was observed [ 176 ]. Preferred binding of Zn 2+ azacrown chelates to uracil has been exploited in developing di- and trinuclear base moiety selective cleaving agents for RNA [ 195 – 196 ].…”