1,9-Dialkoxyanthracene as a ¹O₂-Sensitive Linker

Abstract

We developed a (1)O(2)-sensitive linker based on a 9,10-dialkoxyanthracene structure. Its cleavage in the presence of (1)O(2) is quick and high-yielding. A phosphoramidite containing this fragment was prepared and coupled to a variety of molecular fragments, including nucleosides, fluorescent dyes, and a cholesteryl derivative. On the basis of this building block we prepared a fluorogenic probe for monitoring (1)O(2) in live mammalian cells and visible-light-activated "caged" oligodeoxyribonucleotides. In particular, the fluorogenic (1)O(2) probe is a conjugate of 4,7,4',7'-tetrachlorofluorescein and N,N,N',N'-tetramethylrhodamine coupled to each other via the (1)O(2)-sensitive linker. Fluorescence of the dyes in this probe is quenched. In the presence of (1)O(2), the linker is cleaved with formation of 9,10-anthraquinone and two strongly fluorescent dyes: 4,7,4',7'-tetrachlorofluorescein and N,N,N',N'-tetramethylrhodamine derivatives. We observed that the fluorescence of the probe correlates with the amount of (1)O(2) present in solution. The red-light-activated "caged" oligodeoxyribonucleotides are stable duplexes, which consist of an unmodified strand and a blocker strand. The (1)O(2)-sensitive linker is introduced in the interior of the blocker strand. Upon exposure of the duplex to red light in the presence of In(3+)(pyropheophorbide-a) chloride, the linker is cleaved with formation of the unstable duplex structure. This product decomposes spontaneously, releasing the unmodified strand, which can bind to the complementary target nucleic acid. This uncaging reaction is high-yielding. In contrast, previously reported visible-light-activated reagents are uncaged inefficiently due to competing reactions of sulfoxide and disulfide formation.

In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery

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“Pointsource” Delivery of a Photosensitizer Drug and Singlet Oxygen: Eradication of Glioma Cells In Vitro

“…b,c) . Such oxidation processes resulting in bond cleavage based on singlet oxygen chemistry have been of interest to us.…”

Oxo‐Functionalized Graphene as a Cell Membrane Carrier of Nucleic Acid Probes Controlled by Aging

“…Chemically modified ON‐probes and 2′‐OMe RNAs were prepared on a on a K&A H‐8 DNA/RNA synthesizer using commercially available phosphoramidites DMT‐dG(dmf), DMT‐dA(Bz), DMT‐dC(Bz), DMT‐dT, DMT‐2′‐O‐Methyl‐rG(ib), DMT‐2′‐O‐Methyl‐rA(Bz), DMT‐2′‐O‐Methyl‐rC(Bz), DMT‐2′‐O‐Methyl‐U phosphoramitites (Sigma–Aldrich), and controlled pore glass (CPG, Link Technologies, United Kingdom) as a solid support under standard conditions usually applied in DNA and 2′‐OMe RNA synthesis. Afterwards either 9‐[3‐(4,4′‐dimethoxytrityl)oxypropyloxy]‐10‐(3‐oxypropyloxy)anthracene [(cyanoethyl)( N , N ‐diisopropyl)]phosphoramidite (the anthracene linker), or 5′‐fluorescein‐CE phosphoramidite (Link Technologies, United Kingdom) was coupled manually as previously described ,. Conjugates modified with the anthracene linker were further modified with 5′‐fluorescein‐CE phosphoramidite to give F‐AN‐ON probes for monitoring endoperoxides on the oxo‐G surface.…”