6-Substituted purines containing thienyl or furyl substituents as artificial nucleobases for metal-mediated base pairing

Abstract

The artificial nucleobases 6-(2'-thienyl)-purine (6TP) and 6-(2'-furyl)-purine (6FP) have been investigated in terms of their applicability in metal-mediated base pairs. In principle, these nucleobases should be capable of providing an S,N- and O,N-coordination environment, respectively. Two metal complexes have been synthesized and structurally characterized, using the N9-methylated derivatives of 6TP and 6FP as model nucleobases. The silver(I) complex [Ag(9-Me6TP)(CH3CN)(NO3)]n is of polymeric nature. The thienyl substituent is not involved in metal binding. In contrast, the dinuclear copper(II) complex [Cu(9-Me6FP)Cl2(OH2)]2 clearly shows that the furyl substituent can participate in the coordination of the metal ion. Oligonucleotide double helices comprising a 6TP:6TP or a 6FP:6FP mispair are slightly stabilized in the presence of silver(I). However, a distinction between the formation of a metal-mediated base pair and an unspecific binding event cannot be finally made. Based on these studies, it is proposed that the formation of Hoogsteen-type metal-mediated base pairs should be the more promising alternative compared with the originally anticipated Watson-Crick-type metal-mediated base pairs.

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

“…An analogous 26mer sequence has previously been investigated with other artificial metal-mediated base pairs [25,30], allowing a direct comparison of the results. Similarly, various [14,[26][27][28][29]35].…”

A tridentate “click” nucleoside for metal-mediated base pairing

“…1) The melting temperature T m of duplex I in the absence of any transition metal ion (38.9°C) is amongst the highest observed for all previously investigated duplexes. For comparison, T m was ranging from 21.6 to 30.4°C for base pairs involving bidentate "click" nucleosides [29,30] and from 39.1 to 42.9°C for 6-substituted purines [35]. Merely the duplex comprising a 6TP:6TP mispair (6TP = 6-thienylpurine) has a significantly higher melting temperature (42.9°C) [35].…”

“…2. This particular sequence was chosen because several other metalmediated base pairs have previously been investigated in this sequence context [29,30,34,35], enabling a detailed comparison of their respective properties. Two related duplexes were investigated, i.e.…”

“…For comparison, T m was ranging from 21.6 to 30.4°C for base pairs involving bidentate "click" nucleosides [29,30] and from 39.1 to 42.9°C for 6-substituted purines [35]. Merely the duplex comprising a 6TP:6TP mispair (6TP = 6-thienylpurine) has a significantly higher melting temperature (42.9°C) [35]. Notably, the presence of a canonical base pair in the X:Y position of duplex I leads to melting temperatures of 42.5°C (adenine:thymine) and 45.4°C (guanine:cytosine), respectively [35].…”

Artificial DNA Base Pairing Mediated by Diverse Metal Ions

“…28,42 The artificial nucleobase 6-furylpurine (6FP) (Figure 4c) investigated in this context is of particular interest, as it in principle allows the formation of an Ag(I)-mediated base pair both via its WatsonCrick edge and via its Hoogsteen edge. 28,49 A comparison of both base pairing patterns indicated that the one adopted in parallel-stranded DNA is significantly more stabilizing than that in antiparallel-stranded DNA. Such large increases in T m are an important prerequisite for the use of a metalmediated base pair in a sensor application.…”