| Autor: |
Pavlović Saftić D; Division of Organic Chemistry & Biochemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia., Krošl Knežević I; Division of Organic Chemistry & Biochemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia., de Lera Garrido F; Department of Inorganic and Organic Chemistry and Biochemistry, Faculty of Pharmacy, Universidad de Castilla-La Mancha, C/José María Sánchez Ibáñez s/n, 02008 Albacete, Spain.; Regional Center for Biomedical Research (CRIB), Universidad de Castilla-La Mancha, C/Almansa 13, 02008 Albacete, Spain., Tolosa J; Department of Inorganic and Organic Chemistry and Biochemistry, Faculty of Pharmacy, Universidad de Castilla-La Mancha, C/José María Sánchez Ibáñez s/n, 02008 Albacete, Spain.; Regional Center for Biomedical Research (CRIB), Universidad de Castilla-La Mancha, C/Almansa 13, 02008 Albacete, Spain., Majhen D; Division of Molecular Biology, Ruđer Bošković Institute, 10000 Zagreb, Croatia., Piantanida I; Division of Organic Chemistry & Biochemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia., García Martínez JC; Department of Inorganic and Organic Chemistry and Biochemistry, Faculty of Pharmacy, Universidad de Castilla-La Mancha, C/José María Sánchez Ibáñez s/n, 02008 Albacete, Spain.; Regional Center for Biomedical Research (CRIB), Universidad de Castilla-La Mancha, C/Almansa 13, 02008 Albacete, Spain. |
| Abstrakt: |
The wide use of mono- or bis-styryl fluorophores in biomedical applications prompted the presented design and study of a series of trimeric and tetrameric homo-analogues, styryl moieties arranged around a central aromatic core. The interactions with the most common biorelevant targets, ds-DNA and ds-RNA, were studied by a set of spectrophotometric methods (UV-VIS, fluorescence, circular dichroism, thermal denaturation). All studied dyes showed strong light absorption in the 350-420 nm range and strongly Stokes-shifted (+100-160 nm) emission with quantum yields ( Φ f ) up to 0.57, whereby the mentioned properties were finely tuned by the type of the terminal cationic substituent and number of styryl components (tetramers being red-shifted in respect to trimers). All studied dyes strongly interacted with ds-DNA and ds-RNA with 1-10 nM -1 affinity, with dye emission being strongly quenched. The tetrameric analogues did not show any particular selectivity between ds-DNA or ds-RNA due to large size and consequent partial, non-selective insertion into DNA/RNA grooves. However, smaller trimeric styryl series showed size-dependent selective stabilization of ds-DNA vs. ds-RNA against thermal denaturation and highly selective or even specific recognition of several particular ds-DNA or ds-RNA structures by induced circular dichroism (ICD) bands. The chiral (ICD) selectivity was controlled by the size of a terminal cationic substituent. All dyes entered efficiently live human cells with negligible cytotoxic activity. Further prospects in the transfer of ICD-based selectivity into fluorescence-chiral methods (FDCD and CPL) is proposed, along with the development of new analogues with red-shifted absorbance properties. |
