Expanding the Toolbox of Photoswitches for DNA Nanotechnology Using Arylazopyrazoles

Abstract

Photoregulation is among the most promising tools for development of dynamic DNA nanosystems, due to its high spatiotemporal precision, biocompatibility, and ease of use. So far, azobenzene and its derivatives have shown high potential in photocontrolling DNA duplex hybridization by light-dependent photoisomerization. Despite many recent advances, obtaining sufficiently high photoswitching efficiency under conditions more suitable for work with DNA nanostructures are challenging. Here we introduce a pair of arylazopyrazoles as new photoswitches for efficient and reversible control of DNA hybridization achieved even at room temperature with a low number of required modifications. Their photophysical properties in the native state and in DNA strands result in near-quantitative isomerization rates by irradiation with UV and orange light. To demonstrate the applicability of these photoswitches, we have successfully applied one of them to open and close a DNA hairpin by light at room temperature.

Arylazopyrazole Photoswitches in Aqueous Solution: Substituent Effects, Photophysical Properties, and Host–Guest Chemistry

“…Later, we were able to show that AAPs could be additionally used in CD‐based supramolecular systems, which exhibited similar light‐responsive interactions with β‐CD to those reported for azobenzenes . In recent publications, we have reported several improved light‐responsive systems with the new AAP/CD motif to enable better photocontrol, through which photoswitching of azobenzene restricted the function of the supramolecular system, such as particle assemblies, hydrogels, or DNA compaction …”

“…Despite the need for UV light for the E-Z isomerization of AAPs, they might have potentiala pplications in biological applications and the first examples of AAPs in DNA-based systems have already been reported. [38,41] For the use of azobased photoswitches in in vivo applications, their stability in the reducing cellular environment, which contains compounds such as GSH, is crucial. It is known that some azo compounds undergo photobleaching, depending on their structure and redox potential, through the reduction of the N=Nb ond by GSH.…”

“…[36] In recent publications,w eh ave reported severali mproved light-responsive systemsw ith the new AAP/CDm otif to enable better photocontrol, through which photoswitching of azobenzene restricted the function of the supramolecular system, such as particle assemblies, hydrogels, or DNA compaction. [37][38][39][40][41][42] Similar to azobenzenes, it is expectedt hat for AAPs the properties of the photoswitch will be strongly dependent on the substitution pattern of the molecule. Af irst study on varying the heterocycle wasr eported by Fuchter and co-workersi n 2017 to support this expectation.…”

Light‐Responsive Arylazopyrazole Gelators: From Organic to Aqueous Media and from Supramolecular to Dynamic Covalent Chemistry

“…[54][55][56] In further studies, we have investigated, with others, the properties of AAPs [57] as molecular switches and developeds everal supramolecular systemsr anging from colloidal host-guest complexes, [58,59] foams, [60] adhesives, [61] and DNA complexes. [62,63] Recently,a lso al ight-responsive peptideh ydrogel featuring hostguest interactions betweenA AP peptides and cyclodextrin vesicles was introduced by our group. [64] Ap articularly versatile class of supramolecular polymers assembles from tripodal" core-arm" small molecules.…”

Orthogonally Photocontrolled Non‐Autonomous DNA Walker

“…Adapting the lengths of strands and toeholds can further optimize the efficiency of each photocontrolled strand displacement reaction. This adaptation can result from either the relative amounts of walker and TO strands, or by choosing different photoresponsive moieties …”