Chromophoric Nucleoside Analogues: Synthesis and Characterization of 6‑Aminouracil-Based Nucleodyes

Nucleodyes, visibly colored chromophoric
nucleoside analogues,
are reported. Design criteria are outlined and the syntheses of cytidine
and uridine azo dye analogues derived from 6-aminouracil are described.
Structural analysis shows that the nucleodyes are sound structural
analogues of their native nucleoside counterparts, and photophysical
studies demonstrate that the nucleodyes are sensitive to microenvironmental
changes. Quantum chemical calculations are presented as a valuable
complementary tool for the design of strongly absorbing nucleodyes,
which overlap with the emission of known fluorophores. Förster
critical distance (R0) calculations determine
that the nucleodyes make good FRET pairs with both 2-aminopurine (2AP)
and pyrrolocytosine (PyC). Additionally, unique tautomerization features
exhibited by 5-(4-nitrophenylazo)-6-oxocytidine (8) are
visualized by an extraordinary crystal structure.