DNA‐Triggered Enhancement of Singlet Oxygen Production by Pyridinium Alkynylanthracenes

Abstract

There is an ongoing interest in 1O2 sensitizers, whose activity is selectively controlled by their interaction with DNA. To this end, we synthesized three isomeric pyridinium alkynylanthracenes 2 o–p and a water‐soluble trapping reagent for 1O2. In water and in the absence of DNA, these dyes show a poor efficiency to sensitize the photooxygenation of the trapping reagent as they decompose due to electron transfer processes. In contrast, in the presence of DNA 1O2 is generated from the excited DNA‐bound ligand. The interactions of 2 o–p with DNA were investigated by thermal DNA melting studies, UV/vis and fluorescence spectroscopy, and linear and circular dichroism spectroscopy. Our studies revealed an intercalative binding with an orientation of the long pyridyl‐alkynyl axis parallel to the main axis of the DNA base pairs. In the presence of poly(dA : dT), all three isomers show an enhanced formation of singlet oxygen, as indicated by the reaction of the latter with the trapping reagent. With green light irradiation of isomer 2 o in poly(dA : dT), the conversion rate of the trapping reagent is enhanced by a factor >10. The formation of 1O2 was confirmed by control experiments under anaerobic conditions, in deuterated solvents, or by addition of 1O2 quenchers. When bound to poly(dG : dC), the opposite effect was observed only for isomers 2 o and 2 m, namely the trapping reagent reacted significantly slower. Overall, we showed that pyridinium alkynylanthracenes are very useful intercalators, that exhibit an enhanced photochemical 1O2 generation in the DNA‐bound state.

Methyl Viologens of Bis‐(4’‐Pyridylethynyl)Arenes – Structures, Photophysical and Electrochemical Studies, and their Potential Application in Biology

“…Intriguingly, 3M showed an opposite fluorescence response for GC‐DNA (Figure 8, total quenching) in comparison to AT‐DNA (Figure 8, strong increase), in accordance with reported data [39] . The same type of response was previously observed for proflavine and some pyrene derivatives, and was attributed to the more pronounced electron‐donating properties of guanine compared to other nucleobases [45] .…”

“… Chemical structures of the compounds discussed in this paper ( 3M was very recently reported with a sulphate counter‐anion, [39] and herein, was synthesized and investigated with a triflate counter‐anion).…”

“…In addition, investigation of the energy barrier of their rotamers, [38] in combination with circular dichroism (CD) studies, can provide an in‐depth understanding of such materials. While our manuscript was in preparation, a detailed study on bis‐ N ‐methylated ( o / m / p ) bis‐(pyridiniumethynyl)anthracenes, reported by Linker et al., [39] revealed intriguing photophysical and photochemical properties, their strong interaction with ds‐DNAs, and photo‐induced DNA damage, based on singlet oxygen production. However, it remained unclear whether the large arene, anthracene, is essential for these properties, and what biological applications there might be of such fluorescent, potentially bioactive dyes.…”

“…However, it remained unclear whether the large arene, anthracene, is essential for these properties, and what biological applications there might be of such fluorescent, potentially bioactive dyes. We conducted a very detailed investigation on the multi‐faceted utility of methyl viologen compounds derived from bis‐(4’‐pyridylethynyl)arenes (arenes=benzene, tetrafluorobenzene, and anthracene, the latter one only having been reported very recently with a sulphate counter‐anion [39] ), their crystal and molecular structures, photophysical properties including two‐photon absorption, electrochemical properties, and their applications in biology as promising dyes for DNA‐targeting and theranostic purposes. Herein, we present these results.…”

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

“…A last but effective strategy to localize 1 O 2 production, is using PSs able to bind certain targeted DNA structures. Some very recent examples are reported by the group of Linker, who reported on the use of pyridinium alkynylanthracenes as PSs featuring an enhanced 1 O 2 generation when binding double stranded DNA structures, in presence of green light, which were successfully applied in the context of PDT [ 309 , 310 ]. Besides the known affinity of certain PSs to dsDNA and RNA, some of the reported dyes exhibit preferences in binding alternative secondary structures, such as G4s ( Figure 19 C), and they can therefore be used to confine 1 O 2 generation, increasing their potential therapeutic effect [ 311 ].…”