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

It was demonstrated that styrylquinolizinium derivatives may be applied as photoswitchable DNA ligands. At lower ligand:DNA ratios (≤1.5), these compounds bind to duplex DNA by intercalation, with binding constants ranging from K b = 4.1 × 104 M to 2.6 × 105 M (four examples), as shown by photometric and fluorimetric titrations as well as by CD and LD spectroscopic analyses. Upon irradiation at 450 nm, the methoxy-substituted styrylquinolizinium derivatives form the corresponding syn head-to-tail cyclobutanes in a selective [2 + 2] photocycloaddition, as revealed by X-ray diffraction analysis of the reaction products. These photodimers bind to DNA only weakly by outside-edge association, but they release the intercalating monomers upon irradiation at 315 nm in the presence of DNA. As a result, it is possible to switch between these two ligands and likewise between two different binding modes by irradiation with different excitation wavelengths.

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

(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.

Interaction of crown ether-annelated styryl dyes with double-stranded DNA.

DNA-binding properties of 15-crown-5-derived mono- and bis-styryl dyes were investigated in the presence of calf thymus DNA. To access the factors that influence the DNA association in the series of these ligands, the structure of the molecules was varied by either changing size of the heterocyclic moiety or altering the position of the styryl substituents. The major binding mode for the monostyryl dyes is intercalation. Notably, binding of the dyes to the nucleic acids leads to a fluorescence enhancement by a factor of up to 54. Therefore, these cationic styryl derivatives may be applied as fluorescent "light-up" probes for DNA detection.

Targeting abasic site-containing DNA with annelated quinolizinium derivatives: the influence of size, shape and substituents.

The interactions of regular DNA and abasic site-containing DNA (AP-DNA) with quinolizinium (1a), the linearly fused benzo[b]quinolizinium (2a), the angularly fused benzo[a]quinolizinium (3a), benzo[c]quinolizinium (4a), and dibenzo[a,f]quinolizinium (5a) as well as derivatives thereof were studied with photometric and viscosimetric titrations (regular DNA), fluorimetric titrations and thermal DNA denaturation experiments (regular DNA and AP-DNA). Whereas the parent quinolizinium ion (1a) and the benzo-annelated derivatives 2a, 3a and 4a exhibit no significant affinity to AP-DNA, additional benzo-annelation in 5a leads to an increased selective stabilization of AP-DNA by this ligand. Hence, the latter compound represents the first example of a ligand that does not require ancillary substituents for efficient AP-DNA stabilization. In addition, studies of derivatives with varied substitution patterns revealed an impact of substituents on the stabilization of the AP-DNA. We discovered that a chloro substituent affects the propensity of a ligand to bind to AP-DNA in a similar way as the methyl substituent and may be employed complementary to the known methyl effect to increase the binding affinity of a ligand.