Reversibly Photoswitchable Nucleosides: Synthesis and Photochromic Properties of Diarylethene-Functionalized 7-Deazaadenosine Derivatives

Abstract

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.

New Unsymmetrical Photochromic 1,2-Diaryleperfluorocyclopentenes Bearing a Naphthalene and Thiophene Moiety

“…Generally, photochromic compounds undergo a photo-induced reversible isomerization process between two isomers with different absorption spectra upon irradiation with light of appropriate wavelength. In order to explore novel diarylethenes with excellent characters, a lot of molecules were designed and synthesized, such as purine, thiazole, pyridine and so on [11][12][13].…”

Ab initio modeling of optical spectra in pH‐sensitive diarylethenes

“…The open to close conversion can be induced by UV irradiation, the back reaction requiring visible light, because the majority of closed DA are thermally stable in standard conditions. DA are extremely versatile and this statement can be illustrated by recent applications that include the straightforward transformation of solar energy into mechanical work [4], the reversible control of living organisms [5], and the efficient labelling of nucleosides [6].…”

Two-Step, One-Pot Synthesis of Visible-Light-Responsive 6-Azopurines

“…3c−3e Similarly, photomanipulation of genetic processes can be achieved through reversible modulation of structure and function of DNA and RNA by incorporating a molecular photoswitch into structures of oligonucleotides. 5 Translation and transcription are essential processes in the cell, and their photoregulation could therefore provide insight into many biological mechanisms. Through these applications, in the past decade both photopharmacology and the application of reversibly photocontrolled oligonucleotides provided important alternatives to optogenetics, 4 which uses genetic manipulation to introduce photoresponsive ion channels to cells.…”

“…5 To the best of our knowledge, position 6 has never been directly modified into a heterocyclic azobenzene, even though it appears to be the most promising position for incorporation of a photoswitch that allows to preserve the original molecular function (see examples A1 – A5 in Figure 1). 10 …”