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Para -N-Methylpyridinium Pyrenes: Impact of Positive Charge on ds-DNA/RNA and Protein Recognition, Photo-Induced Bioactivity, and Intracellular Localisation

Affiliation
Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Košćak, Marta;
ORCID
0000-0003-1905-0115
Affiliation
Division of Molecular Biology, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Pehar, Isabela;
ORCID
0000-0001-6840-6689
Affiliation
Division of Molecular Biology, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Božinović, Ksenija;
ORCID
0000-0002-1503-0574
Affiliation
Department of Chemistry, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India
Kole, Goutam Kumar;
Affiliation
Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Sobočanec, Sandra;
ORCID
0000-0002-9423-9711
Affiliation
Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Podgorski, Iva I.;
ORCID
0000-0003-1049-0237
Affiliation
Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Pinterić, Marija;
Affiliation
Institut für Anorganische und Analytische Chemie, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 17, 35392 Gießen, Germany
Müller-Buschbaum, Klaus;
ORCID
0000-0003-0385-0900
Affiliation
Division of Molecular Biology, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Majhen, Dragomira;
ORCID
0000-0002-9933-446X
Affiliation
Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Piantanida, Ivo;
ORCID
0000-0002-9990-0169
Affiliation
Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074 Würzburg, Germany
Marder, Todd B.

The 2- and 2,7- substituted para -N-methylpyridinium pyrene cations show high-affinity intercalation into ds-DNAs, whereas their non-methylated analogues interacted with ds-DNA/RNA only in the protonated form (at pH 5), but not at physiological conditions (pH 7). The fluorescence from non-methylated analogues was strongly dependent on the protonation of the pyridines; consequently, they act as fluorescence ratiometric probes for simultaneous detection of both ds-DNA and BSA at pH 5, relying on the ratio between intensities at 420 nm (BSA specific) and 520 nm (DNA specific), whereby exclusively ds-DNA sensing could be switched-off by adjustment to pH 7. Only methylated, permanently charged pyrenes show photoinduced cleavage of circular DNA, attributed to pyrene-mediated irradiation-induced production of singlet oxygen. Consequently, the moderate toxicity of these cations against human cell lines is strongly increased upon irradiation. Detailed studies revealed increased total ROS production in cells treated by the compounds studied, accompanied by cell swelling and augmentation of cellular complexity. The most photo-active 2- para -N-methylpyridinium pyrene showed significant localization at mitochondria, its photo-bioactivity likely due to mitochondrial DNA damage. Other derivatives were mostly non-selectively distributed between various cytoplasmic organelles, thus being less photoactive.

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