Chiral‐at‐Metal Silver‐Mediated Base Pairs: Metal‐Centred Chirality versus DNA Helical Chirality

Abstract

When covalently incorporating ligands capable of forming chiral metal complexes into a DNA oligonucleotide duplex, an enantiospecific formation of metal‐mediated base pairs is possible. We have been investigating the chirality of the silver‐mediated base pair P−AgI−P (P, 1H‐imidazo[4,5‐f][1,10]phenanthroline) depending on the number of consecutive P : P pairs within a series of duplexes. Towards this end, both enantiomers of the nucleoside analogue 3‐(1H‐imidazo[4,5‐f][1,10]phenanthrolin‐1‐yl)propane‐1,2‐diol comprising an acyclic backbone were introduced into DNA duplexes, resulting in diastereomeric metal‐mediated base pairs. The same chiral‐at‐metal complex is formed inside the duplex for up to five neighbouring P−AgI−P pairs, irrespective of whether (S)‐P or (R)‐P is used. With six silver‐mediated base pairs, the chirality of the metal complex is inverted for (S)‐P but not for (R)‐P. This indicates an intricate balance of what determines the configuration of the metal complex, the intrinsically preferred metal‐centred chirality or the DNA helical chirality.

Contiguous Silver(I)-Mediated Base Pairs of Imidazophenanthroline and Canonical Nucleobases in DNA Duplexes: Formation of Classical Duplexes versus Homodimer Formation

“…AgNO 3 was used as the source of Ag + . Samples for the mass-spectrometric characterization were prepared as reported elsewhere …”

“…27 Another interesting aspect is observed for P−M n+ −P pairs: due to the nonplanarity of this base pair, it possesses metal-based chirality (Figure 1). 28,29 This metal-based chirality appears to be independent of the applied metal ion. 26,28−30 As the P moiety is typically introduced into the DNA duplex using a chiral GNA backbone (GNA, glycol nucleic acid), 31 complexes are formed.…”

“…A complex interplay exists between metal-based chirality, chirality of the GNA backbone, and number of consecutive metal-mediated base pairs. 29 A recent study showed that six consecutive P−Ag + −P base pairs are required to reduce the interdependency of these different factors. 29 ■ RESULTS AND DISCUSSION General Considerations.…”

“…The Cotton effect is reminiscent of that observed for duplexes bearing six consecutive (S)-P−Ag + −(S)-P base pairs and was previously attributed to the metal-based chirality of an (S)-P− Ag + −(S)-P complex. 28,29 We therefore speculated that a dimer of (S)-P 6 might form intermediately, held together solely by coordinate bonds. This was further investigated by titrating Ag + to a solution of single-stranded (S)-P 6 .…”

“…Another interesting aspect is observed for P –M n + – P pairs: due to the nonplanarity of this base pair, it possesses metal-based chirality (Figure ). , This metal-based chirality appears to be independent of the applied metal ion. ,− As the P moiety is typically introduced into the DNA duplex using a chiral GNA backbone (GNA, glycol nucleic acid), diastereomeric metal complexes are formed. A complex interplay exists between metal-based chirality, chirality of the GNA backbone, and number of consecutive metal-mediated base pairs .…”