Relative Strand Orientation in a DNA Duplex Controls the Nuclearity of a Metal‐Mediated Base Pair

Abstract

1,N6‐Ethenoadenine (ϵA) and cytosine (C) are able to form two different metal‐mediated base pairs. When the glycosidic bonds are arranged in a cisoid manner (i.e., in antiparallel‐stranded DNA), the ϵA:C mispair binds one AgI ion, leading to a mononuclear ϵA‐AgI‐C base pair that contains a synergistic hydrogen bond. In contrast, a transoid orientation of the glycosidic bonds (as found in parallel‐stranded DNA) results in the formation of a dinuclear metal‐mediated base pair ϵA‐AgI2‐C.

Metal‐Modified Nucleic Acids: Metal‐Mediated Base Pairs, Triples, and Tetrads

“…[38] Thea pplication of eAa sa na rtificial nucleobase hence enabled the formation of unprecedented dinuclear metal-mediated base pairs,including eA-Ag I 2 -eAas the first dinuclear metal-mediated homo pair of ap urine derivative (Figure 4d), [32] eA-Hg II 2 -T as the only dinuclear metal-mediated base pair with divalent metal ions, [33] and others. [39] Thestructure proposed for eA-Hg II 2 -T as depicted in Figure 4e slightly deviates from the one suggested in the original report but is more likely to represent the correct one. [15e] Similar to the trinuclear TA P-Ag I 3 -TA Pp air (Figure 3d), the accumulation of positive charge is facilitated by the combination of negatively charged (namely deprotonated) thymine with aligand that enforces aclose spacing of the metal ions.T he total charge of the eA-Hg II 2 -T pair is + 3.…”

Metallmodifizierte Nukleinsäuren: Metallvermittelte Basenpaare, ‐tripel und ‐tetraden

“…[38] Die Nutzung von eAa ls künstliche Nukleobase ermçglichte daher die Bildung neuartiger dinuklearer metallvermittelter Basenpaare,w elche eA-Ag I 2 -eAa ls das erste dinukleare metallvermittelte Homobasenpaar eines Purinderivats (Abbildung 4d), [32] eA-Hg II 2 -T als das einzige dinukleare metallvermittelte Basenpaar mit divalenten Metallionen [33] sowie weitere Beispiele umfassen. [39] Die für eA-Hg II 2 -T vorgeschlagene Struktur wie in Abbildung 4e dargestellt weicht leicht von der in der Originalliteratur vorgeschlagenen ab,ist jedoch vermutlich die korrekte. [15e] ¾hnlich dem trinuklearen TA P-Ag I 3 -TA P-Paar (Abbildung 3d)w ird die Akkumulation positiver Ladung durch die Kombination von negativ geladenem (nämlich deprotoniertem) Thymin mit einem Liganden, der einen geringen Abstand der Metallionen erzwingt, ermçglicht.…”

Metal-mediated base pairs in parallel-stranded DNA

“…Its property to align the N→M vectors in an almost parallel manner has led to the application of εA in a series of other metal-mediated base pairs. When locating a cytosine residue opposite εA, a fascinating influence of the relative strand orientation of the DNA duplex on the number of metal ions per base pair was observed [ 77 ]. When the εA:C pair is present inside an antiparallel-stranded duplex, it incorporates one Ag(I).…”

“…Using the same sequence context, albeit with a parallel alignment of the strands with reversed Hoogsteen base pairing, a dinuclear εA–Ag(I) 2 –C pair is formed ( Scheme 9 ). The Ag···Ag distance within this base pair was calculated as 2.92 Å [ 77 ], suggesting the presence of a stabilizing argentophilic interaction [ 78 ]. The parallel-stranded duplex bearing an εA:C pair is stabilized by ≈20 °C upon incorporation of the two Ag(I) ions.…”

“…Base pairs within an antiparallel-stranded context are displayed in grey, whereas base pairs in a parallel-stranded sequence alignment are shown in black. a) εA–Ag(I)–C with a synergistic hydrogen bond [ 77 ]; b) εA–Ag(I) 2 –C [ 77 ]; c) εA–Hg(II) 2 –T [ 79 – 80 ]. R, R’ = DNA backbone.…”