Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**

Abstract

We report the first cellular application of the emerging near-quantitative photoswitchp yrrole hemithioindigo,b yr ationally designing photopharmaceutical PHTub inhibitors of the cytoskeletal protein tubulin. PHTubsa llow simultaneous visible-light imaging and photoswitching in live cells,d elivering cell-precise photomodulation of microtubule dynamics,a nd photocontrol over cell cycle progression and cell death. This is the first acute use of ah emithioindigo photopharmaceutical for high-spatiotemporal-resolution biological control in live cells.I ta dditionally demonstrates the utility of near-quantitative photoswitches,b ye nabling ad arkactive design to overcome residual backgroundactivity during cellular photopatterning.This work opens up new horizons for high-precision microtubule researchusing PHTubsand shows the cellular applicability of pyrrole hemithioindigo as av aluable scaffold for photocontrol of ar ange of other biological targets.

A cross-conjugation approach for high-performance diaryl-hemithioindigo photoswitches

“…Since one hydrogen atom remains at the double bond it is threefold substituted in the core chromophore structure. HTIs were employed early on in the photopharmacological or chemical biology context 24,[37][38][39][40] and found their way into supramolecular chemistry, [41][42][43][44] molecular machine building, [45][46][47][48][49][50][51][52][53] or molecular logic systems. 54 However, particularly steep progress has been made since facile fourfold double-bond substitution became synthetically available.…”

Reversible Photocontrol of Microtubule Stability by Spiropyran‐Conjugated Tau‐Derived Peptides

“…In particular, light of different wavelengths can reversibly change the structures of photochromic molecules, such as azobenzenes, which is useful for reversible switching of active and inactive states [9–12] . For instance, various photoswitches conjugated to microtubule‐binding drugs, such as taxanes, colchicines, and their mimics, have been developed to modulate and image microtubules in living cells and in vivo [13–20] . Moreover, light can reversibly control different functions of dynamic nanomaterials, such as assembly/dissociation and cargo pickup/release, through azobenzene‐bearing DNA conjugated to the outer surface of microtubules [21–23] .…”