Methyl Viologens of Bis‐(4'‐Pyridylethynyl)Arenes – Structures, Photophysical and Electrochemical Studies, and their Potential Application in Biology. Issue 40 (30th May 2022)

• Record Type: Journal Article
• Authors: Kole, Goutam Kumar; Košćak, Marta; Amar, Anissa; Majhen, Dragomira; Božinović, Ksenija; Brkljaca, Zlatko; Ferger, Matthias; Michail, Evripidis; Lorenzen, Sabine; Friedrich, Alexandra; Krummenacher, Ivo; Moos, Michael; Braunschweig, Holger; Boucekkine, Abdou; Lambert, Christoph; Halet, Jean‐François; Piantanida, Ivo; Müller‐Buschbaum, Klaus; Marder, Todd B.
• Is Part Of: Chemistry. Volume 28:Issue 40(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-30
• Subjects: cell imaging -- DNA/RNA binding -- methyl viologen -- singlet oxygen -- two-photon absorption; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202200753
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A series of bis‐(4'‐pyridylethynyl)arenes (arene=benzene, tetrafluorobenzene, and anthracene) were synthesized and their bis‐ N ‐methylpyridinium compounds were investigated as a class of π‐extended methyl viologens. Their structures were determined by single crystal X‐ray diffraction, and their photophysical and electrochemical properties (cyclic voltammetry), as well as their interactions with DNA/RNA were investigated. The dications showed bathochromic shifts in emission compared to the neutral compounds. The neutral compounds showed very small Stokes shifts, which are a little larger for the dications. All of the compounds showed very short fluorescence lifetimes (<4 ns). The neutral compound with an anthracene core has a quantum yield of almost unity. With stronger acceptors, the analogous bis‐ N ‐methylpyridinium compound showed a larger two‐photon absorption cross‐section than its neutral precursor. All of the dicationic compounds interact with DNA/RNA; while the compounds with benzene and tetrafluorobenzene cores bind in the grooves, the one with an anthracene core intercalates as a consequence of its large, condensed aromatic linker moiety, and it aggregates within the polynucleotide when in excess over DNA/RNA. Moreover, all cationic compounds showed highly specific CD spectra upon binding to ds‐DNA/RNA, attributed to the rare case of forcing the planar, achiral molecule into a chiral rotamer, and negligible toxicity toward human cell lines at ≤10 μM concentrations. The anthracene‐analogue exhibited intracellular accumulation within lysosomes, preventing its interaction with cellular DNA/RNA. However, cytotoxicity was evident at 1 μM concentration upon exposure to light, due to singlet oxygen generation within cells. These multi‐faceted features, in combination with its two‐photon absorption properties, suggest it to be a promising lead compound for development of novel light‐activated theranostic agents. Abstract : Methyl‐viologens containing π‐extended bis( N ‐methylpyridiniumethynyl)arenes (arene=benzene, tetrafluorobenzene, anthracene) were crystallographically characterized and their electrochemical properties and one‐ and two‐photon absorption and fluorescence spectra were measured. With DNA/RNA, while the benzene and tetrafluorobenzene analogues bind in grooves, the anthracene analogue intercalates due to its large aromatic moiety, and aggregates within the polynucleotide when in excess over DNA/RNA. The latter compound localizes within lysosomes, preventing its interaction with cellular DNA/RNA, but exhibited cytotoxicity upon photoexcitation, due to 1 O2 generation within cells.