Silver(I) Coordination in Silver(I)‐Mediated Homo Base Pairs of 6‐Pyrazolylpurine in DNA Duplexes Involves the Watson–Crick Edge

Abstract

DNA duplexes comprising 6-(1H-pyrazol-1-yl)-9Hpurine (6PP), 1-deaza-6PP (1D 6PP), 7-deaza-6PP (7D 6PP) and 1,7-dideaza-6PP (1,7D 6PP) 2'-deoxyribonucleosides, respectively,w ere investigated towards their ability to form metalmediated base pairs in the presenceo fA g I .I n6 PP and 7D 6PP,t he Ag I ion can coordinate to the nucleobase via the endocyclic N1 nitrogena tom, that is, via the Watson-Crick edge. In contrast, this nitrogen atom is not available in 1D 6PP and 1,7D 6PP,s ot hat in 1D 6PP an Ag I coordination is only possible via the Hoogsteen edge (N7). Reference duplexesw ith eithera denine:adenine mispairs or canonical adenine:thymine base pairs were used to investigatet he impact of the pyrazolyl moiety on the Ag I-binding properties. To determine the thermala nd structurald uplex stabilities in the absence or presence of Ag I ,a ll duplexes weree xamined by UV and circulardichroism spectroscopics tudies. These investigations shed light on the questiono fw hether N1-or N7-coordination is preferred in purine-based metal-mediated base pairs.

Silver(I)‐mediated hetero base pairs of 6‐pyrazolylpurine and its deaza derivatives

“…It remains unclear if this asymmetric coordination pattern is also present in the 6PPÀ Ag I À 6PP, 7D 6PPÀ Ag I À 6PP, and 6PPÀ Ag I À 7D 6PP base pairs, as these could in principle also contain tetra-coordinate Ag I ions as predicted previously. [16] 3) A similar [2 + 1] coordination pattern is predicted for the respective hetero base pairs in parallel-stranded DNA, too. However, in this less stable duplex configuration, a [2 + 2] coordination environment cannot be ruled out completely, as essentially the same melting temperatures were observed upon the addition of Ag I to duplexes bearing 6PP:6PP, 1D 6PP:6PP, 7D 6PP:6PP, and 1,7D 6PP:6PP mispairs, respectively.…”

“…However, it also shows that the presence of a pyrazolyl substituent suffices for the nucleobase in the purine strand, suggesting a [2+1] coordination mode of the Ag I ions. It remains unclear if this asymmetric coordination pattern is also present in the 6PP−Ag I −6PP, 7D 6PP−Ag I −6PP, and 6PP−Ag I − 7D 6PP base pairs, as these could in principle also contain tetra‐coordinate Ag I ions as predicted previously [16] …”

“…The present study is an extension of the previously reported work on 6PP and its derivatives in Ag I ‐mediated base pairing [16] . In particular, it focuses on heteroleptic Ag I ‐mediated base pairs.…”

“…The sequences were chosen to correlate with those of the previous study. [16] To evaluate the Ag I -binding properties of the antiparallelstranded duplexes, their melting temperatures were determined in the presence of increasing amounts of Ag I by means of temperature-dependent UV spectroscopy. When a metalmediated base pair is formed, its formation is typically accompanied by an increase in the duplex melting temperature T m until all designated metal-binding sites are saturated.…”

“…Recent studies on Ag I ‐mediated homo base pairs of 6PP, 1D 6PP, 7D 6PP, and 1,7D 6PP nucleobases in antiparallel‐stranded duplex DNA had indicated that metal‐mediated base pairing occurs via the Watson‐Crick edge, i. e. that the purine N1 position is important for the complexation of Ag I [16] . In the present study, this investigation was extended to Ag I ‐mediated hetero base pairs and to parallel‐stranded DNA.…”