4-(2′-Pyridyl)imidazole as an artificial nucleobase in highly stabilizing Ag(I)-mediated base pairs

Abstract

A new artificial nucleoside 2 comprising 4-(2'-pyridyl)imidazole as the nucleobase was devised and incorporated into a series of DNA oligonucleotide duplexes. The propensity of 2 to form metal-mediated homo and hetero base pairs was investigated in various 13mer and 26mer duplexes. The artificial nucleoside readily forms Ag(I)-mediated homo base pairs of the type 2-Ag(I)-2, in which the Ag(I) ion resides in a [2 + 2] coordination environment. In addition, the combination with the previously established imidazole nucleoside 1 leads to the formation of Ag(I)-mediated hetero base pairs (2-Ag(I)-1 and 1-Ag(I)-2) with a [2 + 1] coordination environment. With an increase in the melting temperature of ΔT m = 21.8 °C upon the formation of a Ag(I)-mediated base pair, the 2-Ag(I)-1 pair with the 13mer duplex is the most stabilizing Ag(I)-mediated base pair so far. Generally, the impact of the formation of a metal-mediated base pair on the properties of the DNA duplex was found to be significantly more prominent for shorter, intrinsically less stable duplexes.

6-Pyrazolylpurine as an Artificial Nucleobase for Metal-Mediated Base Pairing in DNA Duplexes

“…Similarly to 6PP–Ag(I)–6PP, the Ag(I) ion may bind via N1 or via N7. In both cases, a [2+1] coordination environment is proposed for the metal ion, in analogy to what has been found in other Ag(I)-mediated base pairs [ 26 , 33 ]. Weak additional binding via one of the carbonyl oxygen atoms cannot be ruled out though.…”

“…As the formation of coordinate bonds between the artificial nucleobases and the metal ion typically leads to an increased stability of the duplex [ 2 ], monitoring the T m often represents a good indication for the formation of a metal-mediated base pair. Exceptions from this rule are rare, but are sometimes found in the case of non-planar metal-mediated base pairs [ 24 , 25 ] or when the metal-free duplex is exceptionally stable [ 26 ]. Figure 1 shows the melting curves of the duplex comprising a 6PP:6PP base pair in the absence and presence of one equivalent of AgNO 3 .…”

Stable Hg(II)-mediated base pairs with a phenanthroline-derived nucleobase surrogate in antiparallel-stranded DNA

“…At first, this discrepancy appears surprising, considering that fact that the base pairs should only differ in the relative orientation of their glycosidic bonds (cisoid vs. transoid). However, this may very well be due to the different length of the oligonucleotides under investigation, as previous publications had indicated that the thermal stabilization induced by metal-mediated base pair formation typically is larger for shorter oligonucleotides [59], as is the case here.…”

Triggering Copper(II)-Mediated Base Pair Formation by Light

“…It is a well-known phenomenon that metal-mediated base pair formation exerts a larger stabilizing effect if the stability of the metal-free state is reduced. 38 In summary, the study of duplexes II−IV shows that the most reliable light-triggered formation of an H− Cu(II)−H base pair is achieved when both hydroxypyridone residues initially carry an NPP protecting group.…”