Incorporation of Ruthenium Polypyridyl Complexes Into DNA Oligonucleotides by Copper-Free Click Chemistry.

Alternative methods for the preparation of naïve libraries for SELEX experiments are in dire need, particularly when hydrophobic, bulky, and complex modification patterns are considered. Here, we explore the first steps toward the preparation of libraries equipped with ruthenium polypyridyl complexes using strain-promoted azide-alkyne cycloaddition (SPAAC) reactions. We demonstrated that dsDNA products can be efficiently equipped with dibenzocyclooctyne (DIBAC) moieties using a suitable modified nucleoside triphosphate and primer extension (PEX) reactions or PCR. The resulting dsDNA products can then be further modified using SPAAC and ruthenium polypyridyl complexes equipped with azide moieties, permitting the installation of >10 complexes. Finally, dsDNA can be efficiently converted into the corresponding modified ssDNA using magnetoseparation. These results offer the possibility of producing longer oligonucleotides equipped with complex modification patterns and open the way to SPAAC-click-SELEX methodologies.