Interfering with mitosis is a potential cancer therapy strategy. However, the lack of controllability of anti-mitotic drugs in cell growth suppression causes severe side effects and limits their clinical utility. Herein, we developed an azobenzene-based photoswitchable inhibitor of CENP-E, a mitotic kinesin required for chromosome transportation. The new inhibitor enabled reversible photoswitching of CENP-E activity with ~10fold change in IC50 between cis and trans photoisomerization states both in vitro and in living cells. It also enabled repeatable photoswitching of CENP-E-dependent chromosome congression and hence mitotic progression with UV/Vis light illumination cycles. Using this technique, we could specify the exact process of mitotic progression in which CENP-E plays an indispensable role. Our data demonstrate the power of photochemical approach for highly controllable mitotic interference as well as for discovery of precise molecular functions in dynamic cellular processes.
We demonstrate photoresponsive cholesteric liquid crystals (CLCs) doped with glycomacrocyclic azobenzene derivatives, which exhibit large conformational changes, providing dynamic control of helical superstructures in response to a light stimulus. An unprecedented shortening of the helical pitch length and the empowerment of helical twisting power up to 500% are observed upon trans (E) to cis (Z) photoisomerization. Light-driven dynamic helix twisting and untwisting behavior affords the first example of glycomacrocyclic 2 azobenzenes-based CLCs which can drive the mechanical movement of micro-objects. Two modes of rotations -two-directional or one-directional rotational motion (crankshaft mode)are realized. In particular, the latter mode based on the reversible cholesteric texture transition between homogeneous stripes and focal conics leads to the accumulation of the rotation angles achieving the amplified mechanical movements.
A molecular system inducing an
accumulative unidirectional rotation
motion of glass flakes with about 100 μm in size is introduced.
The molecular system is a chiral nematic liquid crystal containing
a chiral azobenzene derivative which shows a reversible E–Z photoisomerization accompanying a large
helical twisting power change. A film of the molecular system shows
different texture change paths upon UV and visible light irradiations
inducing “E to Z”
and “Z to E” photoisomerizations,
respectively, of the chiral azobenzene dopant. Namely, a polygonal
fingerprint texture inducing the rotation of glass flakes on the film
surface was maintained during UV irradiation, while a focal conic
texture inducing no rotation of glass flakes emerged during visible
light irradiation. As a result, cycles of the alternative irradiation
of UV and visible lights afforded many rotations toward a single direction
of the glass flakes which can be considered as a continuous conversion
of light energy to mechanical work. We may compare the effect of this
molecular system converting “back and forth” structural
change between E and Z isomers of
the chiral azobenzene to a continuous rotational motion of glass flakes
with the crankshaft effect converting a piston-like motion to a rotational
motion seen in engines in the real world.
Water structure modification by urea and temperature has been studied in aqueous solution by analyses of changes in hydrogen bonding and extent of aggregation. ABSTRACT Water absorption peaks in near-infrared (NIR) and attenuated total reflectance (ATR)-Fourier transform infrared (FTIR), spectroscopy at different temperatures both in the absence and presence of urea have been analyzed to investigate hydrogen bonding in aqueous solution by perturbations of temperatures and concentration of urea. Concentration dependent basic spectra of aqueous urea solutions represent different clusters in the system originated from the difference of the extent of self-aggregation of urea molecules and water-urea interactions. Derivative and deconvoluted spectra confirm the presence of different structural components or clusters in pure water; but in presence of urea a new strong water cluster could be identified for the first time after certain concentration of urea. The degree of perturbation has been evaluated by 2D correlation and difference spectroscopy. Apparent molar volume, free energy change of activation (∆G), change in enthalpy of activation (∆H) and entropy of activation (∆S) for viscous flow of water in presence and absence of urea have been analyzed. The comprehensive analyses help to infer different extent of aggregation of urea molecules and formation of clusters by water-urea interactions in aqueous urea solutions.
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