Photo-triggered Traceless Staudinger Ligation Reaction and its Applications in Bioconjugation

Description

The use light to control the course of a chemical/biochemical reaction is an attractive idea because this control can be easily administered with high precision and very fine spatial resolution. Indeed, photo-regulated processes have already found many applications in materials and microelectronic fabrication. The rapidly growing fields of chemical biology and cell biology are also beginning to recognize the advantage of photo-regulation, and are trying to realize the photo-control of bioconjugation for biolabeling and bio-imaging purposes. Two of the most commonly adopted bioconjugation processes are the “Click” reaction and the Staudinger ligation reaction. The former is a [3+2] cycloaddition reaction between an azide and an alkyne, that may require the use of Cu(I) catalysts. The latter is a spontaneous and clean reaction between azides and triarylphosphines to form iminophosphoranes, which can further be hydrolyzed to stable amides. There is already one recent report on photo-regulated “Click” reaction, but, to the best of our knowledge, there is no report on any photo-triggered Staudinger ligation reaction. While there were several previous studies on the photolysis of phosphonium compounds, most of them have focused on the photolytic generation of carbocations rather than paying attention to the possible co-generation of the phosphines. With this view, we designed a thioester-bearing anthracenylmethyl dipehnylphosphonium compound that showed very promising Staudinger ligation properties upon photoexcitation. The aim of this project is to further develop this anthracenylmethyl phosphonium system for photo-triggered traceless Staudinger ligation. A series of new phosphonium compounds will be designed, synthesized and evaluated for their efficiency in the photo-induction of Staudinger ligation reactions. Bio-imaging probes based on these new compounds will also be developed for the fluoro-tagging of selected biomolecules in live cells. Surface-modifying photo-triggered traceless Staudinger ligation reagents will also be developed to demonstrate the possibility of patterned immobilization of biomolecules on inert substrate using such a photo-regulated approach for biosensing and other biomedical applications.