Diphenylaminostyryl-substituted quinolizinium derivatives as fluorescent light-up probes for duplex and quadruplex DNA

Abstract

E)-2-[1'-((Diphenylamino)styryl)quinolizinium (3a) and 2,2'-{( phenylimino)-bis[(E)-1'',1'''-styryl]}-bis[quinolizinium] (3b) were synthesized, and their interactions with duplex DNA and quadruplex DNA were investigated with a particular focus on their ability to operate as DNA-sensitive fluorescent probes. Due to the significantly different size and steric demand of these quinolizinium derivatives they exhibit different binding modes. Thus, 3a intercalates into duplex DNA and binds through π stacking to quadruplex DNA, whereas 3b favours groove binding to both DNA forms. The emission intensity of these compounds is very low in aqueous solution, but it increases drastically upon association with duplex DNA by a factor of 11 (3a) and >100 (3b) and with quadruplex DNA by a factor of >100 (3a) and 10 (3b), with emission bands between 600 and 750 nm. † Electronic supplementary information (ESI) available: Experimental procedures, additional spectroscopic data, and 1 H and 13 C NMR spectra of 3a and 3b. See

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

“…In contrast, the very low emission intensity of 3d did not change upon the addition of ct DNA. The fluorescence light-up effects of the ligands 3a-c upon association with DNA resembled the ones observed for other styryl-substituted quinolizinium derivatives [62][63][64][65][66][67]. Accordingly, the emission enhancement most likely resulted from the accommodation of the ligand in the constrained binding site of the DNA, which led to a restricted conformational flexibility.…”

“…As the quinolizinium ion has been established as a versatile platform for the development of DNA intercalators [60], we identified styryl-substituted quinolizinium derivatives as a promising basis for the search for photoswitchable DNA binders based on the photocycloaddition-photocycloreversion equilibrium. In fact, some selected styrylquinolizinium derivatives have already been shown to bind to DNA [61][62][63][64][65][66][67], however, their photocycloaddition reaction and the propensity of the corresponding photodimers to release the DNA-binding ligand have not been reported so far. Herein, we report on the photochemical and DNA-binding properties of the selected styrylquinolizinium derivatives 3a-d and demonstrate their ability to operate as photoswitchable DNA ligands.…”

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

“…In the meantime, numerous other styryl derivatives were reported as efficient “light-up” probes for G4-DNA and RNA, validating the potential of this molecular scaffold (Fig. 1) [22,33,60–63]. Nevertheless, the structural determinants for the desired properties of the probes (i.e., high selectivity for G4-DNA or G4-RNA with respect to double-stranded or single-stranded nucleic acids, high fluorimetric response and quantum yield, low background fluorescence) are still poorly understood, mostly due to the lack of comparative studies.…”

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

“…The spirooxazine-quinolizinium conjugates 3a and 3b were synthesized by the base-catalyzed reaction [60,62,64,65] of 2-methylquinolizinium (2a) [66,67] or coralyne (2b) [68] with the 5'-formyl-substituted spirooxazine 1b [48,49,69] (Scheme 2 Scheme 2: Synthesis of the spirooxazine-quinolizinium conjugates 3a and 3b. and Scheme S1, Supporting Information File 1).…”

“…For this purpose, we chose the quinolizinium ion as the cationic aryl substituent because it has been shown that derivatives thereof have a great potential to serve as functional units in DNA-binding ligands [54], fluorescent dyes and chemosensors [55][56][57][58][59]. Furthermore, we have already demonstrated that styryl-substituted quinolizinium derivatives exhibit ideal photophysical and DNA-binding properties to be used as DNA-sensitive fluorescent probes in cell imaging [60][61][62] or as photoswitchable DNA ligands [63]. Therefore, we were interested in a combination of the photochromic properties of the spirooxazine moiety with the advantageous photophysical and biological properties of the quinolizinium ion to develop photoswitchable functional quinolizinium derivatives.…”