Mechanistic Studies of Photo-triggered Traceless Staudinger-Bertozzi Ligation Reaction

Description

“Click Chemistry” refers to the establishment of versatile chemical linkages betweenmolecular units via a series of “spring-loaded” chemical reactions under mild conditions.Amongst a variety of “click” reactions, some require photo-activation to react. Thesephoto-triggered “click” processes enable precise spatial and temporal control of themolecular conjugation events and are much welcomed in the fields of syntheticchemistry, materials sciences and chemical biology. However, other than a few examples,most of the “photo-click” processes demand relative high photo-activation energy(excitation wavelength < 400 nm) to initiate and are, therefore, not very compatible tobiomedical applications as high-energy photo-excitation may induce photo-toxicity in invitro and in vivo systems. Our research team has developed an arenylmethylphosphonium-based photo-triggered traceless Staudinger-Bertozzi ligation system thatcan “photo-click” molecular units with peptide bonds. At the moment, the optimalexcitation wavelength of the system is 376 nm. Preliminary theoretical energy-levelcalculation suggests that this may be altered by perturbing the electronic properties ofthe arenyl and phenyl moieties of the phoshonium salts. In this project, we willinvestigate the mechanism of the photolysis of the arenylmethyl phosphonium system,and the related benzhydryl phosphonium system, by laser flash photolysis. A series ofnew phosphonium salts with various electron-donating and withdrawing substituents totheir arenyl/benzhydryl and phenyl components will be synthesized to evaluate theirphoto-induced Staudinger-Bertozzi ligation reactivity. With a better understanding ofthe mechanism of the photo-triggering Staudinger-Bertozzi ligation process, reagentsresponsive to different excitation wavelengths can be developed. Selective and sequential“photo-click” processes can then be realized for bioconjugation, materials fabrication &functional surface modification.