Click Chemistry in the NIR
The ability to trigger the coupling of two molecules via light is an important tool in various fields of scientific research including chemistry, biology and material science. A range of efficient light induced ligation methodologies exist that allow fast, efficient and orthogonal linkage of two moieties in a spatial- and temporal- resolved manner. However, to date the majority of the coupling techniques utilize UV light as a trigger. The application of such a high energy irradiation can cause photo-damage through decomposition or byproduct formation to many (bio)organic species. In addition, for in vivo applications, the depth penetration UV light is limited, due to absorbance of excitation light by tissue. Therefore strategies allowing photo-coupling reaction to occur at longer wavelengths are highly sought.
The teams of James Blinco, Christopher Barner-Kowollik (Queensland University of Technology and Karlsruhe Institute of Technology) and Si Wu (Max Plank Institute for Polymer Research) have combined the chemistry of NIR absorbing upconversion nanoparticles (UNCPs) with the established nitrile imine-mediated tetrazole-ene cycloaddition (NITEC) reaction to yield a novel photoligation technique that can be activated at 980nm. Full conversion of the reagents and an exclusive formation of the desired cycloadducts were observed and the enhanced penetration ability of the NIR trigger wavelength was demonstrated with successful through-tissue reactions. The much milder light stimulus was also verified through ligation of bioactive biotin moiety where full conversion to the ligated molecule is observed with no decrease in biotin bioactivity. All of the formed cycloadducts also exhibited NIR-fluorescence, which helps facilitate their detection during in vivo applications.
Citation: P. Lederhose, Z. Chen, R. Müller, J. P. Blinco, S. Wu, C. Barner-Kowollik, Angew. Chem. Int. Ed. 2016, 55, 12195.