Design And Reaction Mechanism’s Study On Phototrigger Of Blebbistatin Derivatives

Photocages can spatial and temporal control to accurately release the various chemicals and bioactive groups when excited by light.Therefore,they has great application value in many fields and many scientific researchers focus on photocages.However,the maximum absorption wavelength of most photocages are concentrated in the ultraviolet region.The weak ability of ultraviolet light to penetrate biological tissues which limits the application of photocages in cells.More importantly,prolonged exposure of cells or tissues to intense UV light results in irreparable damage.Meanwhile,the low photolysis efficiency and photolysis quantum yield of some photocages also greatly limit their practical application.To design and develop the maximum absorption wavelength in visible region photocages and to improve the photochemical properties of photocages are hotspots in current research.In addition,the water solubility of photocages will also affect their application in medicine and biology.Blebbistatin（Bleb）,as an actin inhibitor,has good biocompatibility and cell membrane permeability.Based on the above description,in this paper,Bleb-X compounds（Bleb-Cl and Bleb-Br）,Bleb and Bleb derivatives（Bleb-OCH₃,Bleb-OBz and Bleb-OCH₃-OBz）were synthesized.Two parts of researchs were conducted to study those molecules.（1）The photochemical properties of Bleb-X were studied through UV-Vis absorption spectrum,steady-state photolysis experiment,photolysis quantum yield experiment and two-photon excitation experiment.The study found that Bleb-X was broken the C-X bond and released the leaving group under blue light excitation or two-photon excitation（near-infrared）;Meanwhile,the increase of the proportion of water would improved the photolysis efficiency and photolysis quantum yield.Combined with product analysis,C-X heterolysis experiment and TD-DFT theoretical calculation,the photolysis mechanism of Bleb-X was explored.It is found that Bleb-X undergoes intramolecular charge transfer（ICT）during photolysis,resulting in C-X bond heterolysis and ICT is the driving force;Then,the products and by-products were formed by resonance conversion or aromatization,respectively.（2）The photochemical properties of Bleb derivatives were studied through UV-Vis absorption spectrum,steady-state photolysis experiment,photolysis quantum yield experiment and two-photon excitation experiment.The results show that Bleb derivatives were broken the C-O bond and released the leaving group under blue light excitation or two-photon excitation（near-infrared）.Meanwhile,to introduce electron donating group（-OCH₃）on Bleb’s D ring can improve the photolysis efficiency and photolysis quantum yield.The photolysis mechanism of Bleb derivatives was explored by transient absorption spectra and TD-DFT theoretical calculation.It was found that water was involved in the photolysis process.