p-Stilbazole Moieties As Artificial Base Pairs for Photo-Cross-Linking of DNA Duplex

Abstract

In this study, we report a photo-cross-linking reaction between p-stilbazole moieties. p-Stilbazoles were introduced into base-paring positions of complementary DNA strands. The [2 + 2] photocycloaddition reaction occurred rapidly upon light irradiation at 340 nm. Consequently, duplex was cross-linked and highly stabilized after 3 min irradiation. The CD spectrum of the cross-linked duplex indicated that the B-form double-helical structure was not severely distorted. NMR analysis revealed only one conformation of the duplex prior to UV irradiation, whereas two diastereomers were detected after the photo-cross-linking reaction. Before UV irradiation, p-stilbazole can adopt two different stacking modes because of rotation around the single bond between the phenyl and vinyl groups; these conformations cannot be discriminated on the NMR time scale due to rapid interconversion. However, photo-cross-linking fixed the conformation and enabled discrimination both by NMR and HPLC. The artificial base pair of p-methylstilbazolium showed almost the same reactivity as p-stilbazole, indicating that positive charge does not affect the reactivity. When a natural nucleobase was present in the complementary strand opposite p-stilbazole, the duplex was significantly destabilized relative to the duplex with paired p-stilbazole moieties and no photoreaction occurred between p-stilbazole and the nucleobase. The p-stilbazole pair has potential as a "third base pair" for nanomaterials due to its high stability and superb orthogonality.

Substituents Have a Large Effect on Photochemical Generation of Benzyl Cations and DNA Cross‐Linking

“…[6] For example, p-stilbazole, [12] coumarin, [13] psoralen, [14] and 3-cyanovinylcarbazole analogues [15] have been reportedt of orm DNA cross-links with pyrimidine nucleotides through[ 2 + +2] photocycloaddition. In general,t hree major mechanisms have been identified for the photoinduced DNA cross-linking process.T hese are photocycloaddition, alkylation via quinone methides( QMs), or alkylation via carbocations.…”

Photoresponsive Self‐Assembled DNA Nanomaterials: Design, Working Principles, and Applications

“…However, significant amount of space is required for its photoisomerization because rotation of the benzene ring is involved by breaking the CC π bond and then rotating the CC σ bond . It is confirmed that photoisomerization of stilbene would not happen when it is intercalated in a double‐stranded DNA . Upon UV light irradiation (e.g., 300–400 nm), spiroyran was switched from a closed, nonplanar form into an open, planar merocyanine form with highly π‐conjugated system.…”

Coumarin‐Induced DNA Ligation, Rearrangement to DNA Interstrand Crosslinks, and Photorelease of Coumarin Moiety

“…Moreover, a number of photosensitive analogues efficiently form crosslink products with dT or dC by [2+2] cycloaddition reaction upon photo irradiation at wavelengths >300 nm. Many of them showed photoreversibility, such as psoralen, azobenzene, p ‐stilbazole, 3‐cyanovinylcarbazole, and others. The DNA crosslinking adducts formed with these compounds can be cleaved into single‐stranded DNA upon photo irradiation at different wavelengths.…”