Synthesis And Characterization Of Indenocoumarin-based Photosensitive Protecting Groups

Photosensitive protective groups(PPGs)are photolabile compounds that can "cage " the activity of functional molecules through covalent bond to obtain inactive precursors.When the precursors are excited by lights,functional molecules can be released instantaneously.Due to the non-contact and non-invasive nature of lights,PPGs have a great potential to be employed in biopharmaceutical applications.However,the excitation wavelength of the classical PPGs usually falls in the UV range,which is both detrimental to the biological systems and has limited penetration depths in tissues.Therefore,developing novel PPGs that can be excited by long wavelengths is crucial for biological applications.To address this issue,structural modification on coumarin PPG was proposed herein.The good biocompatible,high uncaging yields and maximal absorption that close to visible region make coumarin PPGs attractive in various fields.To further red shift the absorption maximum of coumarin PPGs so that they can be excited by long wavelengths,fluorene was introduced into the coumarin skeleton in this paper to prepare a series of novel indenocoumarin PPGs:1.Indenocoumarin PPG A containing diethylamino group was prepared by multi-step reactions using fluorene as starting material.The difference of optical properties between A and commercially available coumarin PPG DEACM was studied systematically.Results show that when excited by 365 nm light,the photolytic efficiencies of DEACM caged benzoic acid precursors are superior to A caged counterparts.However,when excited by 405 nm light,the photolytic efficiency of the precursors depends on the p Ka value of the leaving group.PPG A caged p-chlorobenzoic acid and p-cyanobenzoic acid,both have low p Ka values,show higher uncaging quantum yields than their respective DEACM caged counterparts.When excited at465 nm visible light,DEACM caged benzoic acids completely lose their photolytic ability,but PPG A caged benzoic acids display better uncaging efficiency than those excited at both 365 nm and 405 nm wavelengths.These results prove that our designed indenocoumarin PPG A has better long wavelength photoresponsiveness than DEACM and is favorable for biological applications.2.Five indenocoumarin PPGs B-F with extended D-π-A or A-π-A conjugation were synthesized from 9-dimethylfluorene.The photochemical properties of four PPGs were characterized by using p-substituted benzoic acids as leaving groups.Results show that the photolytic efficiency of PPG with push-pull molecular structure is significantly higher than those with pull-pull molecular structure,indicating that the push-pull electronic structure is more favorable to the photolytic performance of these fused coumarin PPGs.We hope that our discovery will pave a way to the design of novel fused coumarin PPGs for various applications.