Date Awarded


Document Type


Degree Name

Master of Science (M.Sc.)




Douglas D Young

Committee Member

Lisa M Landino

Committee Member

William R McNamara


The terminal alkyne is one of the most widely used chemical moieties in chemical biology. Thanks to the relative absence of this functional group in biology, it has become a widespread functional handle for a plethora of biorthogonal chemistries. Our group has extended the scope of this functionality by developing a biological variant of the Glaser-Hay coupling, which brings together two terminal alkynes to form a diyne linkage. However, our initial findings revealed that the chemistry is plagued by protein degradation due to a deleterious copper(II) hydroxyl intermediate. Herein we extend the scope of the terimanl alkyne be developing a biological variant of the Cadiot-Chodkiewicz coupling, which brings together a bromoalkyne and a terminal alkyne to form a diyne linkage. Unlike the Glaser-Hay, the Cadiot-Chodkiewicz is thought to be net redox neutral. We found that this chemistry is biologically compatible and does indeed reduce copper(II)-mediated cytotoxicity while increasing rates of diyne formation. Finally, we extend our findings on diyne-forming chemistries by applying this conjugation to a variety of projects, ranging from undergraduate teaching labs, bioconjugate preparation, and protein function, thereby expanding the scope of this conjugation strategy.



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