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

•A tridentate “click” nucleoside for metal-mediated base pairing has been prepared.•A novel Ag(I)-mediated base pair with [3 + 1] coordination geometry is reported.•The metal-free homo base pair is also highly stable.

A new silver(I)-mediated base pair comprising an artificial nucleoside with the tridentate ligand 6-(1H-1,2,3-triazol-4-yl)-2,2′-bipyridine and a complementary imidazole nucleoside has been established within a B-DNA double helix. In the absence of any transition metal ion, a DNA duplex containing one such hetero base pair is slightly less stable than a comparable duplex with canonical base pairs. Upon the addition of AgNO3, a silver(I)-mediated base pair with a [3 + 1] coordination environment is formed, accompanied by an increase in thermal stability of about 5 °C. UV and CD spectroscopic analyses provide clear proof for the coordination of the silver(I) ion to the DNA. In contrast, a DNA duplex comprising a central homo base pair of two 6-(1H-1,2,3-triazol-4-yl)-2,2′-bipyridine entities does not form a stabilizing metal-mediated base pair, as this would require a non-planar [3 + 3] coordination environment and a concomitant loss of π stacking interactions. The artificial nucleoside carrying the tridentate ligand belongs to a new family of “click” nucleosides, which are conveniently accessible from 2-deoxy-β-d-glycosyl azide via a copper-catalyzed Huisgen 1,3-dipolar cycloaddition with an alkyne-bearing ligand, and significantly extends the applicability of these “click” nucleosides.

Graphical abstractA new silver(I)-mediated base pair involving a novel tridentate “click” nucleoside and a complementary imidazole nucleoside has been successfully incorporated into a B-DNA double helix.Figure optionsDownload full-size imageDownload as PowerPoint slide