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

• Published in: Chemistry : a European journal Vol. 28; no. 40; pp. e202200753 - n/a
• Main 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.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 15.07.2022; Wiley Subscription Services, Inc; Wiley-VCH Verlag; John Wiley and Sons Inc
• Subjects: Absorption; Anthracene; Anthracenes; Aromatic compounds; Benzene; Biology; cell imaging; Cell lines; Chemical Sciences; Chemistry; Chemistry, Multidisciplinary; Crystal structure; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA/RNA binding; Electrochemical analysis; Electrochemistry; Emission analysis; Grooves; Humans; Hydrocarbons; Lead compounds; Lysosomes; Medicinal Chemistry; methyl viologen; Molecular Structure; or physical chemistry; Paraquat; Photon absorption; Photons; Physical Sciences; Ribonucleic acid; RNA; Science & Technology; Single crystals; Singlet oxygen; Theoretical and; Toxicity; two-photon absorption; DEOXYRIBONUCLEIC-ACID; OPTICAL-PROPERTIES; TRIARYLBORANE CHROMOPHORES; methyl viologen; CIRCULAR-DICHROISM; singlet oxygen; DNA; PI-CONJUGATION; two-photon absorption; cell imaging; INTERCALATING NUCLEIC-ACIDS; ETHIDIUM-BROMIDE; 2-PHOTON ABSORPTION PROPERTIES; COORDINATION POLYMERS; RNA binding; SINGLET-OXYGEN; DNA/RNA binding; DNA/RNA Binding; Singlet oxygen; Methyl Viologen
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202200753

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. 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 1O2 generation within cells.