Tera M Luedtke NW 2019 Metabolic incorporation of bioorthogonal functional groups into chromatin, followed by copper-free conjugation reactions, often gives low yields due to steric hindrance. Here we report that a cationic Sondheimer diyne derivative "DiMOC" rapidly reacts with azide groups in duplex DNA that are otherwise unreactive toward aliphatic cyclooctynes such as bicyclo[6.1.0]nonyne (BCN). DiMOC reversibly intercalates into duplex DNA and undergoes tandem strain-promoted cross-linking of two different azide groups to give DNA-DiMOC-"X" cross-links, where "X" theoretically represents a fluorescent probe, affinity tag, RNA, protein, carbohydrate, and so forth. As a proof of principle, the metabolic incorporation of azide-modified nucleosides into cellular DNA or RNA, followed by treatment with DiMOC and a fluorescent azide enabled visualization of newly synthesized nucleic acids in whole cells. https://sonar.ch/global/documents/164620 eng info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.bioconjchem.9b00630 info:eu-repo/semantics/altIdentifier/pmid/31697067 Bioconjugate chemistry. - 2019 Azides Cross-Linking Reagents DNA Diynes Fluorescent Dyes Intercalating Agents Molecular Imaging RNA Three-Component Bioorthogonal Reactions on Cellular DNA and RNA. http://purl.org/coar/resource_type/c_6501