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

Sarah Kölsch,Jochen Mattay,Norbert Sewald,Brian O Patrick,Heiko Ihmels

doi:10.3762/bjoc.16.13

Abstract

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 Kb = 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.

Highlights

The association of DNA-targeting drugs with nucleic acids [1,2,3,4,5,6,7,8] is considered one of the essential properties that determine their biological activity [9]
The mixtures of compounds 3a–d with calf thymus DNA (ct DNA) showed clear induced circular dichroism (ICD) and linear dichroism (LD) bands in the absorption region of the ligands that further confirmed the binding of the ligands (Figure 4)
We have shown that appropriately substituted styrylquinolizinium derivatives constitute a new class of photoswitchable DNA ligands

Summary

Introduction

The association of DNA-targeting drugs with nucleic acids [1,2,3,4,5,6,7,8] is considered one of the essential properties that determine their biological activity [9]. There is only one reported example for the use of the reversible photoinduced dimerization of stilbene derivatives as photoswitchable DNA ligand [35], and in this case, the structure of the photoproduct was not fully identified. 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.

Results

Conclusion