Reversibly photoswitchable nucleosides: synthesis and photochromic properties of diarylethene-functionalized 7-deazaadenosine derivatives.

Photochromic nucleosides were designed that combine the structural features and molecular recognition properties of nucleic acids with the light-sensitivity of diarylethenes. Target compounds 1a-c consist of a 7-deazaadenosine unit that is linked to a thiophene as the second aryl functionality via a 1,2-cyclopentenyl linker. These nucleoside analogues undergo a reversible electrocyclic rearrangement, generating strongly colored closed-ring isomers upon irradiation with UV-light, while exposure to light in the visible range triggers the cycloreversion to the colorless opened-ring form. UV-vis spectroscopy, HPLC, and (1)H NMR measurements revealed recognition of complementary thymidine and up to 97% conversion to the thermally stable closed-ring isomers after illumination with UV-light. The required wavelength for ring closure was found to vary depending on the substituents attached to the thiophene moiety. In a first design step, we used this important feature of diarylethenes to shift the switching wavelength from initially 300 nm (1a) to 405 nm (1cH(+)). In a second step, we generated a pair of orthogonal switches, differing enough in their respective switching wavelengths to be controlled independently in the same sample. Finally, a molecular switch was developed that showed both photochromism and acidichromism, thereby illustrating the possibility to gate the spectral properties to multiple stimuli. These new photochromic nucleosides represent useful building blocks for the generation of light-sensitive nucleic acids either by inducing conformational changes upon isomerization or by exploring the different spectral properties of the closed and opened isomers, for example, for use as reversible fluorescence quenchers.